CN101379386A - Portable sample analyzer system - Google Patents
Portable sample analyzer system Download PDFInfo
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- CN101379386A CN101379386A CNA200680053149XA CN200680053149A CN101379386A CN 101379386 A CN101379386 A CN 101379386A CN A200680053149X A CNA200680053149X A CN A200680053149XA CN 200680053149 A CN200680053149 A CN 200680053149A CN 101379386 A CN101379386 A CN 101379386A
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- analyser
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Electro-optical investigation, e.g. flow cytometers
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
Abstract
A system relating to sample analyzers, and more particular, to sample analyzers that are simple to operate and have a reduced risk of providing an erroneous result to a user. In some cases, the sample analyzer may be a portable sample analyzer that includes a disposable fluidic cartridge. The operators of the analyzers need not be trained.
Description
The application requires the rights and interests of the U.S. Provisional Patent Application 60/753,293 of submission on Dec 22nd, 2005.
The application requires the rights and interests of the U.S. Provisional Patent Application 60/755,014 of submission on Dec 29th, 2005.
The application is the part continuation application of the Application No. 10/908,460 of submission on May 12nd, 2005, and it requires the rights and interests of the U.S. Provisional Application 60/571,235 of submission on May 14th, 2004.
The application is the part continuation application of the Application No. 10/908,461 of submission on May 12nd, 2005, and it requires the rights and interests of the U.S. Provisional Application 60/571,235 of submission on May 14th, 2004.
The application is the part continuation application of the Application No. 11/306,508 of submission on Dec 30th, 2005, and described application is the continuation-in-part application of the Application No. 10/950,898 of submission on September 27th, 2004.
The application is the part continuation application of the Application No. 10/938,265 of submission on September 9th, 2004.
Background
The application relates in general to sample analyser, more specifically relates to simple to operate and reduces the sample analyser of the danger that error result is provided.
Chemistry and/or biological analysis are all very important for life science, clinical diagnosis and multiple environment and process monitoring aspect.In some cases, carry out with sample analyser and/or auxiliary carry out the chemistry and/or the biological analysis of sample fluid.According to purposes, sample fluid can be liquid or gas.
Many sample analysers are the sizable equipment that is used at laboratory environment by the professional.In order to use many sample analysers, will prepare before sample is used for sample analyser, must at first handle the sample of collection, as with diluted sample to desired level, add suitable agent, make that sample is centrifugal finishes required separation etc.In order to obtain accurate result, must carry out this type of sample preparation by the professional usually, this may increase and carry out expense and the time that sample analysis needs.
Many sample analysers also need operator intervention in the analysis phase, import additional information or handle sample in addition as needs.This also can increase and carry out expense and the time that required sample analysis needs.And many sample analysers only provide original analysis data output, must be calculated and/or be explained by the professional usually just to draw suitable clinical or other judgement.
The U.S. Provisional Patent Application 60/753,293 that on Dec 22nd, 2005 submitted to is attached to herein by reference.The U.S. Provisional Patent Application 60/755,014 that on Dec 29th, 2005 submitted to is attached to herein by reference.The Application No. 10/908,460 that on May 12nd, 2005 submitted to is attached to herein by reference.The Application No. 10/908,461 that on May 12nd, 2005 submitted to is attached to herein by reference.The Application No. 11/306,508 that on Dec 30th, 2005 submitted to is attached to herein by reference.The part continuation application of the Application No. 10/950,898 that on September 27th, 2004 submitted to is attached to herein by reference.The Application No. 10/938,265 that on September 9th, 2004 submitted to is attached to herein by reference.
General introduction
The present invention relates in general to sample analyser, more specifically relates to simple to operate and reduces the sample analyser that the danger of error result is provided to the user.In some cases, sample analyser can be the portable sample analyzer that comprises disposable fluid box.
The accompanying drawing summary
Fig. 1 is the skeleton view of exemplary sample analyser and box (cartridge);
Fig. 2 is the synoptic diagram of Fig. 1 exemplary sample analyser and box;
Fig. 3 is the more detailed maps of the flow control of displayed map 2 sample analysers and box;
Fig. 4 is the synoptic diagram of some feature of exemplary cartridge;
Fig. 5 is the synoptic diagram that can be included in a plurality of exemplary storage pools in the box;
Fig. 6 is the schematic flow diagram of the illustrative methods of display analysis blood sample;
Fig. 7 is the process flow diagram that shows the illustrative methods that obtains multiple erythrocyte parameter;
Fig. 8 is the schematic flow diagram of the another kind of illustrative methods of display analysis blood sample;
Fig. 9 a, 9b, 9c, 9d, 9e and 9f show pin-every interface (needle-septuminterface), axle-film (shaft-membrane) interface and membrane-membrane interface respectively.
Fig. 9 g shows the table that promotes stream (pusher fluid), solvent soln (lysing solution), nodularization solution (sphering solution) and sheath stream (sheath fluid) cavity diameter;
Figure 10 shows the schematic flow diagram of setting up and operating the illustrative methods of sample analyser;
Figure 11 a is the process flow diagram of the illustrative methods of display operation sample analyser;
Figure 11 b is the process flow diagram of the another kind of illustrative methods of display operation sample analyser;
Figure 12 is the process flow diagram of the another kind of illustrative methods of display operation sample analyser;
Figure 13 is exemplary optics instrumentation plan, can be used for helping to identify in the fluid circuit flow channel when have incorrect or unwanted fluid;
Figure 14 is the synoptic diagram that another kind of exemplary optics is measured, and can be used for helping to identify in the fluid circuit flow channel when have incorrect or unwanted fluid;
Figure 15 is the electrical measurement synoptic diagram, can be used for helping to identify in the fluid circuit flow channel when have incorrect or unwanted fluid;
Figure 16 is another kind of instrumentation plan, can be used for helping to identify in the fluid circuit flow channel when have incorrect or unwanted fluid;
Figure 17 is the synoptic diagram of illustrative examples, can be used for identifying when one or more bubbles or other unwanted particle appear in sample fluid in the flow channel;
Figure 18 is another kind of illustrative examples synoptic diagram, can be used for identifying when one or more bubbles or other unwanted particle appear in sample fluid in the flow channel;
Figure 19 is the illustrative examples synoptic diagram, can be used for identifying when one or more bubbles or other unwanted feature appear in sample fluid in the flow channel;
Figure 20 shows that pressure source can offer exemplary pressure pulse 900 sample fluid in Figure 19 flow channel;
Figure 21 is the illustrative examples synoptic diagram, can help to determine or estimating of fluid loop flow passage in the position of sample fluid end or far-end;
Figure 22-the 23rd, the illustrative examples synoptic diagram can be used for determining when two or more fluids compile in the fluid circuit downstream;
Figure 24 is the synoptic diagram of exemplary instrument and box, and wherein box and instrument are (keyed) of coupling, only allows box to insert in the instrument with correct direction;
Figure 25 is the exemplary cartridge synoptic diagram;
Figure 26 is the exemplary cartridge synoptic diagram that comprises spring driving lancet (spring activated lancet);
Figure 27 has the exemplary cartridge synoptic diagram of removing the film of bubble in the flow channel; With
Figure 28 is the illustrative examples synoptic diagram of flow channel bubble grabber.
Describe in detail
The present invention relates to sample analyser, more specifically relate to simple to operate and reduce the sample analyser of the danger that error result is provided, in some cases, as required, sample analyser can be for example blood analyser such as flow cytometer, hematology analyzer, clinical chemistry analyzer (as glucose analyser, ion analyser, blomelicalbloodgasandelectrolrteanalyzers, dissolved gas analysis instrument etc.), Urine Analyzer or any other suitable analyser.
If the present invention meets some requirement, then himself or can avoid rules supervision with its test of carrying out.Can implement the present invention can be the test of laboratory inspection and rules to provide and/or to carry out, described test is simple and accurate, so that provide the possibility of error result to ignore, perhaps when incorrect the test, can not produce the risk of the patient harm that can know by inference.A kind of type of exempting can be improved amendment (CLIA) from clinical labororatory in 1988.
Fig. 1 is the flow cytometer skeleton view.It is only presented for purposes of illustration to describe stream type cell analyzer, and expection is in case of necessity applicable to other type sample analyser.The exemplary sample analyser shows as 10 usually, comprises shell 12 and movable or disposable cassette 14.Example housings 12 comprise substrate 16, lid 18 with substrate 16 with cover 18 hinges that are connected 20, but this not necessarily needs.In illustrative examples, substrate 16 comprises the first light source 22a, secondary light source 22b and the 3rd light source 22c and the related optical device and the electronic equipment of operation sample analyser needs.Each light source can be single light source or multiple light courcess, depends on purposes.In some cases, the overall dimensions of shell less than 1 cubic feet, less than 1/2 cubic feet, less than 1/4 cubic feet or littler in case of necessity.Equally, the overall weight of shell can less than 10 pounds, less than 5 pounds, less than 1 pound or littler in case of necessity.
Example activity formula box 14 is fit to receive sample fluid by the sample collection mouth, collects mouth and comprise lancet 32 in illustrative examples.In some cases, lancet 32 is retractible and/or spring is housed.When movable box 14 did not use, cap 38 can be used for protecting sample collection mouth and/or lancet 32.
In illustrative examples, 14 pairs of whole blood samples of movable box carry out blood analysis.Lancet 32 can be used for piercing through user finger and obtains blood sample, and it is sucked in the kapillary that the anti-coagulants coating is arranged in the movable box 14 by capillarity.Movable box 14 can be made of fluid circuit, and the some of them fluid circuit forms with the layer structure with etched channels.Yet if desired, expection can comprise that injection moulding or any other suitable preparation process or method constitute movable box 14 by any suitable method.
During use, after blood sample being sucked movable box 14, movable box 14 can be inserted in the shell.In some cases, can when lid 18 is in the release position, movable box 14 be inserted in the shell.Yet, in other cases, can movable box 14 be inserted in the shell by any suitable manner.For example, shell can have the line of rabbet joint, movable box 14 can be inserted in the line of rabbet joint of shell.
Look back the illustrative examples of Fig. 1, movable box 14 can comprise eyelet 26a and the 26b that receives fastening screw 28a and 28b in the substrate 16, can help to aim at and connect the different piece of instrument.Movable box 14 also can comprise the first transparent flow window 30a, the second transparent flow window 30b and the 3rd transparency window 30c, aims at first, second and the 3rd light source 22a, 22b and 22c and first, second and the 3rd photodetector 24a, 24b and 24c respectively.
When lid was moved into the pressurization of off-position and system, lid 18 can be respectively provides pressure receiving port 34a, 34b, 34c and 34d to the example activity formula box 14 by pressure feed mouth 36a, 36b, 36c and 36d with controlled pressure.According to purposes, expection can be used more or less pressure feed and pressure receiving port.Perhaps or in addition, expection can be provided at one or more Micropumps such as electrostatically actuated micro pump (meso pump) on the movable box 14 or wherein, provide the essential pressure in operating fluid loop for movable box 14.Some exemplary electrostatically actuated micro pumps are described in for example U.S. Patent number 5,836,750,6,106,245,6179,586,6,729,856 and 6,767,190, and these patents all transfer the assignee of the present invention, all are attached to herein by reference.
In case pressurization, exemplary instrument can be carried out blood analysis to the blood sample of collecting.In some cases, blood analysis can comprise complete blood count (CBC) analysis, but can carry out other type analysis according to purposes.
For to red blood cell count(RBC) and classification, the part whole blood sample can be told and provided red blood cell measurement passage to movable box 14.Then if desired, can dilute blood sample, red blood cell (on the fly) in real time forms sphere, and the gained sample can be fluid dynamics to be concentrated, and forms core, finally provides to the first cytolytic dose passage.The first cytolytic dose passage can be along the first transparent flow window 30a location of movable box 14, so that the fluid cell can be ask spy by the first light source 22a and the first photodetector 24a optics.In some cases, the first flow sensor can be provided on the movable box 14, measure flow velocity by the first cytolytic dose passage.
In some cases, measurement parameter can comprise for example sample flow rate (FR), Measuring Time (T) duration, diluted sample coefficient (DF), red blood cell count(RBC) (N
RB), platelet count (N
Plt), each cell dia (drbc) and each cellular hemoglobin concentration (CHC).From these parameters, can calculate many red blood cell analytical parameters, comprise as red blood cell count(RBC) (RBC=N
RB/ (DF * FR * T)), platelet count (Plt=N
Plt/ (DF * FR * T)), mean cell hemoglobin concentration (MCHC=＜CHC 〉), mean corpuscular volume (MCV=(π/6) *＜drbc
3), mean cell hemoglobin content (MCH=(π/6) *＜drbc
3* CHC 〉), the relative dispersion of distribution (RDW=[(π/6) * drbc
3The standard deviation of]/MCV), packed cell volume parameter (Hct=RBC * MCV) and/or hemoglobin concentration (Hb=MCHC * Hct).
In some instances, also with some blood sample guiding absorptiometry passages.The absorptiometry passage can be along the 3rd transparency window 30c location of movable box 14, so that blood sample can be ask spy by the 3rd light source 22c and the 3rd photodetector 24c optics.Flow sensor can be provided on the movable box 14, measure the flow velocity that enters or pass through the absorptiometry passage.The absorptiometry passage can be provided by the absorption of incident light that is provided by the 3rd light source 22c.The absorption level of measuring can be provided as overall or mean cell hemoglobin concentration reading in the blood sample.
For to white blood count and differential, the part whole blood sample can be told and provided leucocyte measurement passage to movable box 14.Then if desired, can dilute blood sample, red blood cell can dissolve in real time, and the gained sample can be fluid dynamics to be concentrated, and forms core, finally provides to the second cytolytic dose passage.The second cytolytic dose passage can be along the second transparent flow window 30b location of movable box 14, so that the fluid cell can be ask spy by the secondary light source 22b and the second photodetector 24b optics.Flow sensor can be provided on the movable box 14 to measure flow velocity by the second cytolytic dose passage.In some cases, the leucocyte parameter of measurement for example can comprise three (3) or (5) partly leukocyte differentiation, total leukocyte counting and/or positive axis (on-axis) leucocyte volume.Also can measure or calculate other parameter according to purposes.
Fig. 1 shows a kind of exemplary sample analyser and box assembly.Yet expection can be used other sample analyser configuration.For example, sample analyser 10 and movable box can be similar to the description of the U.S. Patent application 2004/0211077 of authorizing Schwichtenberg etc., and it is attached to herein by reference.
In some cases, sample analyser 10 is adapted at patient care point as doctor clinic, household or on-the-spot other local use.10 needs of sample analyser seldom or not need professional training to use reliably outside laboratory environment, there has been this sample analyser 10 can help the streaming of sample analysis process, minimizing expense and medical worker's burden, increase to analyze the convenience of many patient's samples, comprise relatively frequently to monitor/patient of analyzing blood.
During operation, sample analyser 10 can receive the sample of collection, and as the whole blood of collecting, in case start analyser, sample analyser 10 can be handled sample automatically, and the information of making clinical judgment is provided for the user.In some instances, sample analyser 10 can show or print quantitative result (as within the preset range and/or outside), so that the user does not need to calculate or explain.
Fig. 2 is the synoptic diagram of Fig. 1 exemplary sample analyser and box.Describe in detail as mentioned, in illustrative examples, substrate 16 can comprise the optical device and the essential control and the processing electronic equipment 40 of Operations Analyst instrument of a plurality of light sources 22, association.Substrate 16 also can comprise battery 42, transformer or other power supply.Shown in lid 12 have pressure source/flow control piece 44 and a plurality of photodetectors 24 with related optical device.
In some cases, preparation (as dissolving, nodularization, dyeing, dilution and/or other processing) blood sample, fluid dynamics is concentrated in one or more (on-board) cytolytic dose passages going along with such as cytolytic dose passage 50 then, forms core.In illustrative examples, the transparent flow window of the movable box 14 of cytolytic dose passage 50 processes is as the first transparent flow window 30a.A series of light sources 22 can make light pass through core fluid via mobile window 30a with related optical device in the substrate 16.A series of photodetectors 24 also can be via the scattering and the non-scattered light of the window 30a reception core that flows with related optical device.Controller or processor 40 can receive the output signal of self-detector 24 arrays, can distinguish and/or count the selected cell that exists in the core fluid.
Expected activity formula box 14 can comprise fluid controll block 48, helps the speed of at least some fluids in the movable box 14 of control.In illustrative examples, fluid controll block 48 comprises the speed that can predict various fluids and with the flow sensor of speed report to controller or processor 40.Controller or one or more control signals of processor 40 scalable provide it to pressure source/flow control piece 44 then, reach required pressure, thereby obtain the required fluid velocity of proper operation analyser.
Because blood and other biology waste liquid can spread disease,, be positioned at exemplary cells measurement channel 50 downstreams so movable box 14 can comprise waste liquid pool 52.Waste liquid pool 52 can receive and store the fluid in the movable box 14.When test is finished, can take out the movable box 14 of analyser, for example be discarded in the container compatible with the biology waste liquid.
Fig. 3 is more detailed synoptic diagram, the flow control of displayed map 2 sample analysers and box.In illustrative examples, the pressure source/flow controller 44 of lid 18 provides 5 kinds of controlled pressures, comprises that sample promotes (P) pressure 36a, dissolving (L) pressure 36b, nodularization (SP) pressure 36c, sheath stream (SH) pressure 36d and dilution (D) pressure 36e.These are used to illustrate, and according to purposes, that expecting pressure source/flow controller 44 can provide is more, still less or different pressure (as the dyeing pressure to color pond).And expection is covered 18 and can not comprised pressure source/flow controller 44.The substitute is, as required, movable box 14 can comprise pressure source going along with such as pressurized air pond, one or more Micropump such as above-mentioned electrostatically actuated micro pump or any other suitable pressure source.Light source and detector array do not show at Fig. 3.
In illustrative examples, pressure source 36a provides pressure to blood sample pond 62 through promoting stream 65, and pressure source 36b provides pressure to dissolving tank 64, and pressure source 36c provides pressure to nodularization pond 66, pressure source 36d provides pressure to sheath flow pool 68, and pressure source 36e provides pressure to diluting tank 70.
In an illustrative examples, each pressure source can comprise first pressure chamber that receives input pressure and second pressure chamber of controlled pressure to movable box is provided.First valve can be used for the pressure of first pressure chamber controllably is released in second pressure chamber between first pressure chamber and second pressure chamber.The pressure of second pressure chamber controllably can be released in the atmosphere with second valve of second pressure chamber's fluid communication.But this authorized pressure source/flow controller 44 provides each pressure receiving port to the movable box 14 with controlled pressure.But each valve can be the little valve array of the electrostatically actuated of individual operation and control, as is described in as U.S. Patent number 6,240,944, and it is attached to herein by reference.Perhaps, each valve can be the little valve array of electrostatically actuated, and described little valve is regulated by the work period pulse feature of control, realizes the flow velocity of control " effectively " or leaks speed (leak rate).If desired, also can use other valve.
Example activity formula box 14 comprises 5 pressure receiving port 34a, 34b, 34c, 34d and 34e, receives the control corresponding pressure from pressure source/flow controller 44 separately.In illustrative examples, pressure receiving port 34a, 34b, 34c, 34d and 34e are passed to controlled pressure storage blood pond 62, dissolving tank 64, nodularization pond 66, sheath flow pool 68 and diluting tank 70 respectively.Assemble for before using at movable box 14, can fill dissolving tank 64, nodularization pond 66, sheath flow pool 68 and diluting tank 70, and by sample collection mouth or the lancet 32 on-the-spot storage blood ponds 62 of filling.
As shown in the figure, flow sensor can be provided in every kind or the selected fluid line.Each flow sensor 80a-80e can measure the speed of corresponding fluids.Flow sensor 80a-80e can be hot gas flow velocity type (thermal anemometer type) flow sensor and microbridge type flow sensor.Microbridge flow sensor is described in as U.S. Patent number 4,478, and 076, U.S. Patent number 4,478,077, U.S. Patent number 4,501,144, U.S. Patent number 4,651, and 564, U.S. Patent number 4,683,159 and U.S. Patent number 5,050429, all be attached to herein by reference.
Perhaps or in addition, sensor 80a-80e can be used for one or more features of test fluid, as temperature conductivity, specific heat, fluid density, resistivity and/or other characteristic of fluid, identify or verify that as helping the fluid that is passing flow channel is expection fluid or expection fluid type.What this was used for flow channel in the time of can helping to verify concrete analysis or operation is the expection fluid really.Whether available controller follow procedure detection of desired fluid is used for flow channel really, in some cases, gives a warning and/or cuts off sample analyser.
The output signal of each flow sensor 80a-80e can be provided to controller or processor 40.As shown in the figure, controller or processor 40 can provide control signal to pressure source/controller 44.For example, in order to control to the blood sample applied pressure, when blood sample speed drops to when being lower than first predetermined value, controller or processor 40 can be opened first valve between first pressure chamber and second pressure chamber in pressure source/controller 44, and the pressure of first pressure chamber controllably is released into second pressure chamber.Equally, when blood sample speed increases to when being higher than second predetermined value, controller or processor 40 can be opened second valve, emit the pressure of second pressure chamber.Controller or processor 40 can be controlled the speed of lytic agent, modulizer, sheath stream and thinning agent by similar fashion.
In some cases, controller or processor 40 can detect one or more changes of passing the flow channel flow velocity.Flow velocity changes and for example to be attributable to, and one or more bubbles in the flow channel, the flow channel that causes as blood sample coagulation is inaccessible or part is inaccessible, do not need in the flow channel or external object and/or other negative characteristics of flow channel.In some cases, can use some further features of rise time, fall time or flow velocity.Can make controller or processor 40 follow procedures detect this category feature of flow velocity, in some cases, give a warning and/or cut off sample analyser.
Hot gas flow velocity type flow sensor generally includes heating element (can produce one or more thermal pulses when energy supply in fluid), also comprises one or more thermal sensors (being positioned at heating element upstream and/or downstream to detect one or more thermal pulses).The speed that fluid passes flow channel may arrive the time correlation that a spaced heat sensor needs from heating element with thermal pulse.
In some cases, hot gas flow velocity type flow sensor can be used for test fluid thermal conductivity and/or specific heat.The change of fluid thermal conductivity and/or specific heat can be corresponding to the change of characteristic of fluid, as not needing in the change (blood sample coagulation) of fluid state, fluid bubbles, the fluid or foreign body etc.Perhaps or in addition, hot gas flow velocity type flow sensor can be used for detecting one or more characteristic of fluid such as thermal conductivity, specific heat etc., so that for example help to identify or fluid that flow channel is passed in checking is expection fluid or expection fluid type.What this was used for flow channel in the time of can helping to verify concrete analysis or operation is the expection fluid really.In some instances, expection controller or processor 40 can be by thermal conductivity and/or the specific heat test fluid feature of monitoring through the fluid of overfire air stream speed type flow sensor.Can make the negative characteristics (as bubble) of controller or processor 40 follow procedure test example such as fluid, and/or whether the expection fluid be used for flow channel really, in some cases, give a warning and/or cut off sample analyser.
In some cases, can provide impedance transducer and flow channel fluid communication.Controller or processor 40 are connected with impedance transducer.The change of fluid impedance can be pointed out the change of characteristic of fluid, and changing in (blood sample coagulation), fluid bubbles, the fluid as fluid state does not need or external object, correct fluid type etc.Therefore, in some instances, expection controller or processor 40 can be by the fluid impedance test fluid feature of monitoring through impedance transducer.
Also can provide substantially at 110 downstream valves that show.Downstream valve 110 can be opened/close to controller or processor 40 as required.For example, downstream valve 110 can keep closing until system pressurizeing fully.This can help prevent blood, lytic agent, modulizer, sheath stream and thinning agent before system pressurizes fully in the incoming fluid loop 86.And may command downstream valve 110 helps to carry out some test, as the zero flow test etc.In another example, for example when lid is closed, can open downstream valve 110 by mechanical effect.
Fig. 4 is the synoptic diagram of some feature of example activity formula box.Overall as 100 demonstrations of example activity formula box can be similar to the movable box 14 that Fig. 1-3 shows and describes.Should understand 100 in movable box and be used to illustrate, this example is applicable to many microfluid boxes, no matter its form, function or configuration are how.For example, this example is applicable to the movable box that is fit to flow cytometry, hematology, clinical chemistry, blood chemical analysis, urinalysis, blood gas analysis, virus analysis, bacterial analysis, electrolyte measurement etc.Also expect the movable box such as the movable box 100 of available any suitable material or material system (for example glass, silicon, one or more polymkeric substance or any other suitable material or material system) or material or material system combined preparation native system.
Example activity formula box 100 comprises that first measures the path 10 2 and the second measurement path 10 4, but can use more or less measurement passage as required.In illustrative examples, the first measurement path 10 2 is that red blood cell is measured passage, and the second measurement path 10 4 is that leucocyte is measured passage.Movable box 100 receives whole blood sample by blood receiving port 106, by capillarity, known quantity blood is sucked the blood sample that the anti-coagulants coating is arranged store in the kapillary 108.Sample is promoted (P) pressure, and sample promotion (P) pressure 36a as Fig. 3 provides to sample propelling fluid pond, as the sample propelling fluid pond 65 of Fig. 3.When exerting pressure, force sample to promote stream and enter in the blood sample promotion passage 110 from sample propelling fluid pond
In some illustrative examples, valve 112 and flow sensor 114 can be provided in blood sample promotion passage 110 circuits.May command valve 112 is open when needs promotion blood sample passes fluid circuit.Flow sensor 114 can be measured the flow velocity that blood sample promotes stream, thereby measures the blood sample flow velocity of the kapillary 108 that passes the anti-coagulants coating.The flow velocity that flow sensor 114 provides can be used for helping to control the sample that provides to movable box 100 and promotes (P) pressure.
In illustrative examples, whole blood sample is distributed, provide to red blood cell measurement path 10 2 and leucocyte measurement path 10 4 by branch 116.In illustrative examples, valve 118 is provided in branched line, flow into the blood sample that red blood cell is measured path 10 2 with control, provide valve 120 to flow into the blood sample that leucocyte is measured path 10 4 with control.
In some illustrative examples, also valve 126 and flow sensor 128 can be provided in modulizer passage 124 circuits.When needs pushed fluid circuit with modulizer, may command valve 126 was open.Flow sensor 128 can be measured the flow velocity of modulizer, measures the modulizer flow velocity that passes modulizer passage 124.The flow velocity that flow sensor 128 provides can be used for helping controlling by pressure source/controller 44 provides nodularization pressure (SP) to movable box 100.
When normal function operation example sexuality formula box 100, modulizer is pushed in the intersection 130 with the modulizer flow velocity, blood sample is pushed in the intersection 130 with the blood sample flow velocity.Can be by pressure source/controller 44 control blood sample flow velocity and modulizer flow velocitys of Fig. 3.
Sheath can be flowed (SH) pressure, sheath stream (SH) pressure 36d as Fig. 3 provides the sheath flow pool 68 to sheath flow pool such as Fig. 3.When exerting pressure, force sheath stream to enter in the sheath circulation road 134 from sheath flow pool 68.In some illustrative examples, valve 136 and flow sensor 138 can be provided in sheath circulation road 134 circuits.When needs pushed sheath stream in the fluid circuit, may command valve 136 was open.Flow sensor 138 can be measured the flow velocity of sheath stream, can measure the sheath stream flow velocity that passes sheath circulation road 134.The flow velocity that flow sensor 138 provides can be used for helping to control the sheath flowing pressure (SH) that provides to movable box 100.
In illustrative examples, provide to the intersection 140 with sheath stream with sheath stream flow velocity, provide to the intersection 140 with nodularization blood sample (sphered blood sample) with nodularization blood sample flow velocity.Available pressure source/controller, as pressure source/controller 44 of Fig. 3, control nodularization blood sample flow velocity and sheath stream flow velocity.
In some illustrative examples, valve 156 and flow sensor 158 can be provided in lytic agent passage 154 circuits.When needs pushed fluid circuit with lytic agent, may command valve 156 was open.Flow sensor 158 can be measured the flow velocity of lytic agent, measures the lytic agent flow velocity that passes lytic agent passage 154.The flow velocity that flow sensor 158 provides can be used for helping controlling by pressure source/controller 44 provides solution presasure (L) to movable box 100.
When normal function operation example sexuality formula box 100, provide to the intersection 160 with lytic agent with the lytic agent flow velocity, provide to the intersection 160 with blood sample with the blood sample flow velocity.Available pressure source/controller, as pressure source/controller 44 of Fig. 3, control blood sample flow velocity and lytic agent flow velocity.
Sheath can be flowed (SH) pressure, sheath stream (SH) pressure 36d as Fig. 3 provides to sheath flow pool, as the sheath flow pool 68 of Fig. 3.When exerting pressure, force sheath stream to enter in the sheath circulation road 164 from sheath flow pool 68.In some illustrative examples, valve 166 and flow sensor 168 can be provided in sheath circulation road 164 circuits.When needs pushed fluid circuit with sheath stream, may command valve 166 was open.Flow sensor 168 can be measured the flow velocity of sheath stream, can measure the sheath stream flow velocity that passes sheath circulation road 164.The flow velocity that flow sensor 168 provides can be used for helping to control the sheath flowing pressure (SH) that provides to movable box 100.In some cases, it is identical with the flow velocity that passes sheath circulation road 134 to pass the sheath stream flow velocity of sheath circulation road 164.Yet in other cases, the sheath stream flow velocity that passes sheath circulation road 164 is different with the flow velocity that passes sheath circulation road 134.
In illustrative examples, provide to the intersection 170 with sheath stream with sheath stream flow velocity, will dissolve blood sample provides to the intersection 170 to dissolve the blood sample flow velocity.Available pressure source/controller, as pressure source/controller 44 of Fig. 3, control dissolving blood sample flow velocity and sheath stream flow velocity.
In some cases, also can provide the absorptiometry passage.In illustrative examples, will be partly dissolved blood sample provides to absorbing path 180.Valve 182 can be provided pass absorbing path or distinguish 184 so that selectivity allows to be partly dissolved blood sample.Analyser can comprise and illuminate absorbing path or distinguish 184 light source, and detects the detecting device that is not absorbed passage or distinguishes the light that the dissolving blood sample in 184 absorbs.Analyser can be measured the absorption level then, therefrom obtains the hemoglobinometry value based on overall absorption (bulkabsorption), in some cases if desired, shows that as Fig. 8 absorbing path 184 can be positioned at cytolytic dose passage 172 downstreams.In other cases, whole blood sample direct (as from branch 116) can be provided to absorbing path.In this case, absorbing path can be included in the mechanical hook-up that carries out the preceding lysed erythrocyte of absorptiometry.Though example activity formula box 100 is fit to whole blood sample is carried out complete blood count (CBC) analysis, expection can be used other movable box configuration and analysis type as required.
Fig. 5 is a plurality of exemplary storage pool synoptic diagram that can be included in the movable box.In illustrative examples, the movable box 100 of movable box such as Fig. 4 can comprise for example lytic agent pond 64, promotion stream pond 65, modulizer pond 66, sheath flow pool 68, diluent stream pond 70, color pond 190 and waste liquid pool 52.These are used to illustrate, and expection can be with more, still less or different storage pool is provided on the movable box or wherein.
Each storage pool can have different size, holds the appropriate amount fluid and/or the reagent of support activities formula box action required.Diluting tank 70 can hold and be used to dilute the diluted fluid of sample such as whole blood sample of newly arriving.In the illustrative examples of Fig. 4, modulizer and/or lytic agent can be brought into play diluent functions, therefore may must or even not need independent diluting tank 70.Equally, in some instances, can need dyestuff to be added in the leucocyte passage to support leukocyte differential count with color pond such as color pond 190.According to purposes, reagent and/or fluid in the expection storage pool can adopt liquid or lyophilized form at first.
Fig. 6 shows the illustrative methods schematic flow diagram of analyzing blood sample with movable box.In illustrative methods, at first at step 200 blood sample collection.Then, blood sample is provided to the anti-coagulants coatings capillary pipe of movable box.Distribute blood sample then, provide to red blood cell and blood platelet (RBC/P) measurement passage 204 and leucocyte (WBC) measurement passage 206.
In RBC/P measures passage 204, at first as 212 show and make the red blood cell nodularization, be fluid dynamics then and concentrate, and provide with single file along the RBC/P cytolytic dose passage 214 of movable box.When cell passed the analysis area of RBC/P cytolytic dose passage 214, light source 216 as vertical cavity surface emitting laser (VCSEL), impinged upon light on the individual cells.In some cases, provide VCSEL equipment array, have only the VCSEL that aims at the individual cells of passing RBC/P cytolytic dose passage 214 analysis areas to be activated.Some incident lights that VCSEL provides are scattered, and detecting device 218 detects scattered light.In some cases, detecting device 218 can detect anterior angle scattered light (FALS), small angle scattering light (SALS) and large-angle scatter light (LALS).
In some cases, laser (or other) source focuses on RBC/P cytolytic dose passage 214, as the line source that extends or as two independent point sources.RBC and blood platelet in the RBC/P cytolytic dose passage 214 pass through focused light.High-quality collection optical device can be used for forming the picture rich in detail of cell, illumination concentrated on contain on one, the opaque screen (screen) in two or more parallel cracks the rectangular quadratures of flow direction in the longitudinal axis in described crack and the RBC/P cytolytic dose passage 214.Fracture interval is from can being that for example the average cell of expection is at interval in the RBC/P cytolytic dose passage 214.The opaque screen that contains the crack can be placed one or more detecting devices 218 the place aheads.When cell image passed through the crack, the light that is incident on the crack was smudgy, weakened the signal that arrives detecting device 218, produced width and the proportional pulse waveform of cell dia.When crack, two intervals was provided, two kinds of waveforms can allow to calculate the cell flowing velocity, thereby calculated the cell size.Available this technology obtains high s/n ratio, thus easy counting event and evaluation various kinds of cell incident.Pulse width and amplitude also can be distinguished some cell types.
In some cases, make on the double slit hole before cell and light source image all are imaged on detecting device 218.The double slit hole provides how much holes of sharp outline and high s/n ratio with counting cells.As above discuss, come the signal of endokinetic fissure can allow accurately to measure cell flow rate, can allow to calculate cell dia then.
In some cases,, can when this is analyzed, measure multiple parameter, comprise as sample flow rate (FR), Measuring Time (T) duration and diluted sample coefficient (DF) as 220 demonstrations.By output of monitoring detecting device and/or corresponding scattered signal, can measure RBC number (N
RB), platelet count (N
Plt), each cell dia (drbc) and each cellular hemoglobin concentration.
From these parameters, as 282 demonstrations, can calculate multiple red blood cell analytical parameters, comprise as red blood cell count(RBC) (RBC=N
RB/ (DF * FR * T)), platelet count (Plt=N
Plt/ (DF * FR * T)), mean cell hemoglobin concentration (MCHC=＜CHC 〉), mean corpuscular volume (MCV=(π/6) *＜drbc
3), mean cell hemoglobin content (MCH=(π/6) *＜drbc
3* CHC 〉), the relative dispersion of distribution (RDW=[(π/6) * drbc
3The standard deviation of]/MCV), packed cell volume parameter (Hct=RBC * MCV) and/or hemoglobin concentration (Hb=MCHC * Hct).
Measure in the passage 206 at exemplary WBC, at first as 232 show, be fluid dynamics then and concentrate, and provide with single file along WBC cytolytic dose passage in the movable box 234 with erythrocytolysis.Light source 236, as vertical cavity surface emitting laser (VCSEL), with illumination on the individual cells of passing WBC cytolytic dose passage 234 analysis areas.In some cases, provide VCSEL equipment array, have only the VCSEL that aims at the individual cells of passing WBC cytolytic dose passage 234 analysis areas just to be activated.Some incident lights that provided by VCSEL are scattered, and detecting device 238 detects scattered light.In some cases, detecting device 238 detects anterior angle scattered light (FALS), small angle scattering light (SALS) and large-angle scatter light (LALS).In some cases,, can when analyzing, measure multiple parameter, comprise that for example positive axis cell volume, total WBC counting and WBC five (5) partly classify as 240 demonstrations.
Fig. 7 shows the exemplary method flowchart that obtains multiple erythrocyte parameter.In illustrative methods, obtain blood sample in step 260.Then, diluting blood sample to required dilution factor (DF), is shown nodularization as 264.It is concentrated to make the dilution and the haemocyte of nodularization be fluid dynamics then, provides with single file along the RBC/P cytolytic dose passage of movable box.Light source 216 as vertical cavity surface emitting laser (VCSEL) with illumination on the individual cells of passing RBC/P cytolytic dose passage analysis area.Some incident lights that provided by VCSEL are scattered, and available detecting device detects scattered light.In some cases, detecting device detects the anterior angle scattered light (FALS) and the small angle scattering light (SALS) of each cell.Processor etc. can be the mapping of SALS and FALS pair cell diameter parameters and cellular hemoglobin concentration parameter with two kinds of independent scattering parameters of each cell then, and is as follows:
{S
SALSi，S
FALSi}->(drbc
i，CHC
i)
As 270 demonstrations, if scattering S
SALSi+ S
FALSiIntensity is not more than the predetermined detection threshold value, and then control arrives step 268.Yet, if scattering S
SALSi+ S
FALSiIntensity is greater than the predetermined detection threshold value, and then control arrives step 272.Step 272 is determined S
SALSi+ S
FALSiWhether sum is greater than predetermined blood platelet threshold value.If S
SALSi+ S
FALSiSum is not more than predetermined blood platelet threshold value, and then particle " i " is a blood platelet, and control arrives step 274.Step 274 makes platelet count (N
Plt) increasing by 1, step 268 is returned in control.
If S
SALSi+ S
FALSiSum is greater than predetermined blood platelet threshold value, and then cell is a red blood cell, and control arrives step 276.Step 276 makes red blood cell count(RBC) (N
RBC) increasing by 1, control arrives step 278.Step 278 determines whether to reach the scheduled measurement time.If no, then step 268 is returned in control.
In case reach Measuring Time in step 278, then control arrives step 280.Step 280 shows multiple measurement parameter, comprises as sample flow rate (FR), Measuring Time (T) duration, diluted sample coefficient (DF), red blood cell count(RBC) (N
RBC), platelet count (N
Plt), each cell dia (drbc
i) and each cellular hemoglobin concentration (CHC
i).From these parameters, show as step 282, can calculate multiple blood cell analysis parameter, comprise as red blood cell count(RBC) (RBC=N
RBC/ (DF * FR * T)), platelet count (Plt=N
Plt/ (DF * FR * T)), mean cell hemoglobin concentration (MCHC=＜CHC
i, mean corpuscular volume (MCV=(π/6) *＜drbc
i 3), mean cell hemoglobin content (MCH=(π/6) *＜drbc
i 3* CHC
i), the relative dispersion of distribution (RDW=[(π/6) * drbc
i 3The standard deviation of]/MCV), packed cell volume parameter (Hct=RBC * MCV) and/or hemoglobin concentration (Hb=MCHC * Hct), wherein symbol＜X
iRefer to whole cell X
iThe average cell parameter.
Fig. 8 is the another kind of illustrative methods schematic flow diagram of display analysis blood sample.In this illustrative methods, obtain blood sample, provide to the blood sample pond, show as step 300.Then, blood sample is provided to the anti-coagulants coatings capillary pipe of movable box dilution.Then blood sample is distributed, provide to red blood cell and blood platelet (RBC/P) measurement passage 304 and leucocyte (WBC) measurement passage 340.
In RBC/P measures passage 304, with at first nodularization shown in 306 of red blood cell, make it be fluid dynamics then and concentrate, provide with single file along the RBC/P cytolytic dose passage 308 of movable box.First light source 310 is provided in focused beam to pass on the individual cells of RBC/P cytolytic dose passage 308 analysis areas with related optical device as vertical cavity surface emitting laser (VCSEL).In some cases, provide VCSEL equipment array, have only the VCSEL that aims at the individual cells of passing RBC/P cytolytic dose passage 308 analysis areas to be activated.
When individual cells/particle during through the incident beam that focuses on, some light are blocked, scattering or stop that this available detecting device (not shown) detects.When the point of two or more light-resource fousings different interval on RBC/P cytolytic dose passage 308, can detect the leading edge and/or the opisthogenesis of each cell.By measure cell through the focus point of associating to the used time of distance between the next focus point, measure cell speed thereby can measure flow velocity.Measure after the cell speed, can or stop that the time span of light beam is related with cell size and/or cell volume cell blocking-up, scattering.
In some instances, analyser can provide another light source 314 and related optical device.But the related optical device collimated light of light source 314 is measured from axle scattering such as SALS and FALS scattering.As noted above, available SALS and FALS scatterometry red blood cell count(RBC) (N for example
RBC) 316, platelet count (N
Plt) 322, each cell dia (drbc
i), cell volume 318 and each cellular hemoglobin concentration 320 (CHC
i).From these parameters, as above discuss, can calculate multiple blood cell analysis parameter, comprise for example red blood cell count(RBC) (RBC=N
RBC/ DF * FR * T)), platelet count (Plt=N
Plt/ (DF * FR * T)), mean cell hemoglobin concentration (MCHC=＜CHC
i, mean corpuscular volume (MCV=(π/6) *＜drbc
i 3), mean cell hemoglobin content (MCH=(π/6) *＜drbc
i 3* CHC
i), the relative dispersion of distribution (RDW=[(π/6) * drbc
i 3The standard deviation of]/MCV), packed cell volume parameter (Hct=RBC * MCV) and/or hemoglobin concentration (Hb=MCHC * Hct), wherein symbol＜X
iRefer to whole cell X
iThe average cell parameter.
Measure in the passage 340 at exemplary WBC, lysed erythrocyte is suitably injected dyestuff, shows as 342.Make cell be fluid dynamics then and concentrate, provide with single file along the WBC cytolytic dose passage 344 of movable box.Light source 346 as vertical cavity surface emitting laser (VCSEL) with illumination on the individual cells of passing WBC cytolytic dose passage 344 analysis areas.In some cases, provide VCSEL equipment array, have only the VCSEL that aims at the individual cells of passing WBC cytolytic dose passage 344 analysis areas to be activated.
When individual cells/particle during through the incident beam that focuses on, some light are blocked, scattering or stop that this available detecting device (not shown) detects.When the point of two or more light-resource fousings different interval on WBC cytolytic dose passage 344, can detect the leading edge and/or the opisthogenesis of each cell.By measure cell through the focus point of associating to the used time of distance between the next focus point, measure cell speed thereby can measure flow velocity.After measuring cell speed, can or stop that the time span of light beam is related with cell size and/or cell volume with cell blocking-up, scattering.
In some instances, can provide light source 350 and related optical device and/or polarizer.But the related optical device collimated light of light source 350 is measured from axle scattering such as SALS, FALS and LALS scattering, shows as 354.As noted above, available SALS, FALS and LALS scatterometry white blood cell count(WBC) (N for example
WBC) 352, and help to distinguish leucocyte, show as 356.In some cases, the light polarization that provides one or more polarizers that light source is provided, polarization extinction/optically-active level that detecting device detects can be used for helping to distinguish leucocyte, but are not that all examples all need like this.
In illustrative examples, the cell that leaves WBC cytolytic dose passage 344 can be provided to total absorbing path 360.On light source 362 can illumination occur in absorbing path 360 the cell, detecting device 364 can detect the light that is not absorbed by intrinsic cell (resident cell).Therefore absorbing path 360 can be used for measuring total absorption level of intrinsic cell.The absorption level can for example be measured the overall or mean cell hemoglobin concentration of blood sample.The haemoglobin passage can have the optical device of adjusting zero point again, automatic focus and/or calibration.Light source 362 can be the LED that has near the output signal at absorption peak center, therefore can not need filter disc.Available curvette receives and holds sample, with the assessment haemoglobin.Humidity and temperature sensor can be positioned on the card (card), with show measure these parameters at that time with the card article spare of history.The time of card heating or cooling can show the temperature before the operation initialization.Monitoring this type of condition can be relevant with material and solution on the card.Grasp these conditions and can be used as the chance that card or the delamination of box structure were eliminated or obviously reduced to safety practice.
Can realize contamination-freely shifting and mobile fluid by Fig. 9 a-9f interface displayed.In case reagent is stored in the kit of instrument, just has the compressibility problem of each supply line inner fluid from the reagent pond to fluid interface.In order to reach the control of high fidelity fluid flow, should make this problem drop to minimum.Compressibility may be owing to bubble, the bubble dissolved gas that solution produces during from temperature change or from the air of the gas-permeable wall diffusion by supply line.A kind of method that addresses this problem can be that foaming solution such as reagent are evacuated to the valve that can enter the kit waste liquid tank from the instrument flow interface, for example replaces with fresh fluid.In case bubble has been absorbed again or towards to waste liquid, then can turn valve again, makes the fluid/air liquid level build-up to fluid interface.After liquid level build-up was near fluid interface, another problem demanding prompt solution may be the potential possibility that instrument is polluted by blood sample.The flow that can provide several solns to be used to control blood sample and reagent does not need the contact of touch controls simultaneously.
Fig. 9 a and 9b show pin-in the interface, pin 1201 can pierce through barrier film 1202, the liquid that is stored on the instrument is delivered to passage 1203 cards 1204.Flow sensor and controller can be positioned on the instrument.When measuring end taking-up pin 1201, barrier film 1202 seals voluntarily, and card does not leak, and handles easily.Though the reagent that this method can be stored instrument well causes card 1204, sample blood is present on the card, in case needle-penetration barrier film 1202 will contact blood.The pin 1201 of bent at its tip can be designed for need not core (coring) especially can pierce through barrier film.
During operation, can make the pollution of pin 1201 reduce to minimum, have several method to overcome.During mensuration, promote stream flushing needle inside.Measure when finishing available membrane 1202 wiping pins 1201 outsides when taking out pin.The small size of pin 1201 can limit and be retained in the blood volume that its tip end surface is amassed.Instrument can be a heating very fast to the heat sterilization process of needle point, and this is because the geometric similarity of small size and pin and heat transmission latch.Sterilization process can be with experimental results show that.And normally open valve can prevent that any fluid from backflowing in the instrument during outage.
Can mention axle-membrane interface of Fig. 9 c and 9d.In the method, an available end replaces long and thin sample loop with the cylindrical shape sample storeroom of elastic membrane 1206 sealings.Film 1206 can be positioned to be moulded on the shell (molded case) 1207, above sample storage pool 1208.In order to allocate sample, use the described film of leading screw backup by the rotation of micro-stepping motor.This can be a syringe pump in fact, makes axle 1205 backup films 1206 rather than advances the interior piston of syringe cylinder.But the advantage of this method is physical barriers film 1206 pollution abatement problems.
Method can be included in the null displacement (i.e. a contact membranes 1206) of finding axle 1205 after card is installed in the instrument.The stereomutation reaction of sample storeroom may be nonlinear relationship with axial translation, needs calibration.Axle 1205 tips can be at the displacement efficient design.Actual conditions can be that axle running (at full stroke) fully can be sent 80% sample in the storeroom.Film 1206 needs enough to cave in so that not understanding outer being pressed onto of finger/drive membrane and allotment sample.
The membrane-membrane interface can show as Fig. 9 e and 9f.In the method, sample still can be stored at one end in the cylindrical shape storage pool with the elastic membrane sealing.Available have its most advanced and sophisticated drivers 1211 of film 1212 sealing and cause film 1206 displacements.If two films 1206 have contacted with 1212, will drive liquid 1213 pumps to driver 1211 tips film 1212 and 1206 all is out of shape, the equal-volume fluid in the mobile example pond 1208.
Some advantages of this method may be obvious that.The flow sensor technology can be used for the flow velocity of controlling and driving liquid 1213, finally controls sample flow rate.Because it is fluid-operated driving, so film 1206 and 1212 natural easy deformation are to provide high displacement efficient.This method also can be by isolating blood sample pollution abatement problem behind the physics film.
Method finds null displacement after can being included in and in the instrument card being installed, and does not move any blood sample so that film 1212 is contacted just with 1206.The stereomutation of sample storeroom 1208 reaction may with the stereomutation of driver film 1212 departs from linear relation a little, need calibration.Film 1206 on the card must enough cave in so that point not understanding outer being pressed onto/drive membrane 1206 and allotment sample.
The sample loop of Fig. 9 e and 9f is not a gallery, but shallow cylindrical cavity.Film 1212 initially contacts fine (promptly not having air entrapment therebetween) with 1206, and the volume that drives liquid 1213 expansion can make the film deflection repeatably measure (adjustable).
Having dynamics in membrane interface changes.The compliance that elastic membrane is introduced should be little, because the Poisson ratio of typical elastomeric such as silicone rubber and Neoprene is compressible hardly usually in the 0.45-0.50 scope.Basically, elastic body is deformable all, but incompressible; Their shape changes easily but its volume is not easy to change.Therefore, wherein mould membrane-membrane interface that the hard material restriction elastomer shape of shell and driver changes and kinetic results should not occur significantly from the low compliance of elastic body.
The deflection of film 1206 can not be allocated all samples or the reagent that holds in the storeroom.The allotment ratio can characterize with displacement efficient.The efficient of ε=80% should be considered as reasonably.If also suppose the ratio (for example, δ=1/3) of film deflection and chamber diameter, then the displacement volume can be about
V
disp＝εδ(π/4)d
3
Diameter that can following estimation storeroom
d＝((4V
disp/(εδπ))
1/3。
The tabular of Fig. 9 g goes out the storeroom diameter that enough storage samples promotes stream and every kind of reagent, supposes that mensuration will carry out half the time measure R BC, half the time measurement WBC 4 minutes.The big I that is used for reagent storeroom on the card of nodularization solution and sheath solution is considered based on the card of enough sizes.
With the pin that is included in the reagent storage box in the instrument-supply reagent has remarkable advantage every the interface.If small-sized sterilization mechanical hook-up is provided, then can pass through film-type interface or pin-every the interface control blood sample on instrument.
Figure 10 is the illustrative methods schematic flow diagram that shows assembling and operation sample analyser.In illustrative examples, can show use and analyzing blood is analyzed box as 351, can shown in 370, use and analyze with control enclosure helping the performance of check analysis instrument, and/or can shown in 380, use and the analytic set box with help calibration analyte instrument.The blood analysis box all can be installed at every turn carry out blood analysis.Can shown in 372 control enclosure be installed in analyser, cycling service such as every day 1 time shown in 374, what obtain with the check analysis instrument is accurate result.Shown in 376, instrument can show the whether mark in scope of measurement.This mark can be depending on measurement whether in normal, low or high scope.Shown in 380, can be shown in installation calibrating device and operation shown in 384 on the calibration box as 382.Instrument can be regulated the calibration factor that meets calibration shown in 386.Calibration card can be installed in the analyser, to be lower than the frequency of control card, as per 3 months 1 time, with calibration analyte instrument again.Calibration can comprise before the operation or make accurate pearl stream (precisionbead flow) by flow channel after the operation, thereby scaled pulse width for example provides the grain size of passing passage information.
Each box can hold all must fluid and/or composition with the performance corresponding function.Like this, do not need how many trainings just can operate and/or the maintenance analysis instrument, and still obtain accurate result.The sample analyser with movable and/or disposable cassette that provides can be used outside laboratory environment reliably by the personnel of not process professional training, can help to make the streaming of sample analysis process, minimizing expense and medical worker's burden, increase the convenience of many patient's sample analysis, comprise the patient of blood monitoring/analysis that need be quite frequent.System can point out whether reagent and/or sample fluid addle, stalely, contaminated, incorrect or inappropriate maybe can not receive.The final activity of system can comprise not to be carried out analyzing, the result is not provided, error flag etc. is provided.
When shown in 351, using the blood analysis box, can and be placed in the blood analysis box blood sample collection, show as 353 and 355.Can by capillarity or manual pumps blood sample be sucked in the blood analysis box as required.Then can blood analysis is box-packed in the analyser instrument.In illustrative examples, analyser can be aimed at the appropriate section (as light source/photodetector etc.) of blood analysis box and analyser voluntarily then, shows as 357.Then, can push one or more buttons and begin the blood analysis process.In some cases, pressing button etc. not, but only to analyser, can cause analyser to begin to aim at and the blood analysis process with box-packed.
Card can be as 358 operations.In case driving analyser, analyser just can carry out multiple test.For example, analyser can cut out all valves on the blood analysis card, exerts pressure to blocking various fluid intakes.The analyser measurable flow is crossed the flow velocity that card is gone up one or more flow sensors then.Flow should be zero, because all valves are all closed.Yet if flow sensor prompting non-zero points flow velocity, analyser can be calibrated the clear point flow again with flow sensor.This can help to increase the accuracy that flow sensor is measured.Analyser can be checked and begin to remove bubble as required.Perhaps or in addition, but the solidifying of blood in the analyser Survey Operations formula box, the blood sample flow velocity (as using flow sensor) under for example exerting pressure by measuring, if flow velocity is too low for applied pressure, the decidable blood sample solidifies.If can showing, discovery blood clotting, analyser shows the measurement failure.
Analyser can be implemented regularly scheme of blood analysis box then.Blood analysis box regularly scheme can be similar to U.S. Patent Application Serial Number 10/932,662 demonstration of submitting on September 2nd, 2004 and the scheme of describing, and it transfers the assignee of the present invention, is attached to herein by reference.Concrete blood analysis box timing scheme can be depending on the specific design of blood analysis box.Analyser also can verify on the blood analysis box in any cytolytic dose passage whether stable core fluid is arranged, if exist then the position of identifying core fluid.
The blood analysis box can for example dissolve the red blood cell that will be used to measure leukocytic blood sample part then, make the red blood cell nodularization that will be used to measure erythrocytic blood sample part, on the blood analysis box, form core fluid in any cytolytic dose passage, and/or bring into play any other required function.Analyser can provide light to institute's favored area of blood analysis box such as any cytolytic dose passage, detects and passes the light of institute's favored area.
Like this, analyser can be counted and classifies the particle in the sample such as leucocyte, red blood cell, blood platelet etc., shows then, prints, sounds or be user's mark blood analysis result.In some instances, analyser show or print quantitative result (as within the preset range and/or outside), so that the user does not need to calculate or explain.Can be considered and finish measurement, shown in 361, display result.Finally, can take out the blood analysis box of analyser, shown in 363, throw aside.
In the time will controlling operation, can use control enclosure as 370 demonstrations.In some cases, can regularly control operation, as every day 1 time or 1 time weekly.Control enclosure can comprise the control sample with known features.Therefore, when the control sample being analyzed, should obtain known results with analyser.In illustrative methods, control enclosure is contained in the analyser, show as 372.Then, start analyser, as 374 demonstrations, analyser is analyzed and display result, shows as 376.In some instances, analyser show or print quantitative result (as within the preset range and/or outside), so that the user does not need to calculate or explain.Finally, can take out the control enclosure of analyser and throwing aside.If the result of control operation can preferably carry out correcting travel, as correcting travel 380 outside preset range.
In the time will carrying out the correcting travel of 380 demonstrations, can use the calibration box.In some cases, can regularly carry out correcting travel, as 1 time every month, perhaps as required.The calibration box can comprise the calibration sample with known features.Therefore, when calibration sample being analyzed, should obtain known results with analyser.In illustrative methods, will calibrate box-packedly in analyser, show as 382.Then, start analyser,, obtain a plurality of results as 384 demonstrations.The result who obtains when relatively expected results is with correcting travel, analyser can be regulated one or more calibration factors in the storer automatically with calibration analyte instrument again, so that when moving next time, analyser will produce expects or required result, as 386 demonstrations.
Figure 11 a is the process flow diagram of display operation sample analyser illustrative methods.Overall as 400 demonstrations of illustrative methods enter in step 402.Control arrives step 404, wherein blood sample is provided to disposable fluid box.Control arrives step 406 then, wherein disposable fluid box is inserted in the blood sample analysis instrument.Control arrives step 408 then.Step 408 starts the blood sample analysis instrument, and step 410 obtains the blood analysis result from the blood sample analysis instrument, and no longer needs any interaction of blood sample analysis instrument user.Control arrives step 412 then, withdraws from step.
Figure 11 b is the exemplary method flowchart that shows another kind of operation sample analyser.Overall as 500 demonstrations of illustrative methods begin in step 502.Control arrives step 504, wherein blood sample is provided to disposable fluid box.Control arrives step 506 then, wherein disposable fluid box is inserted in the blood sample analysis instrument.Control arrives step 508 then.Step 508 starts the blood sample analysis instrument, and step 510 obtains the blood analysis result from the blood sample analysis instrument, and no longer needs any interaction of blood sample analysis instrument user.Control arrives step 512 then.Step 512 determines that the blood analysis result is whether in preset range.As mentioned above, in some instances, analyser can show or print quantitative result (as within the preset range and/or outside), so that the user does not need to calculate or explain.Control arrives step 514 then, withdraws from step.
Figure 12 is the another kind of exemplary method flowchart of display operation sample analyser.Overall as 600 demonstrations of method enter in step 602.In illustrative methods, can shown in 604, use and analyzing blood is analyzed box, can shown in 620, use and the analysis and Control box helping the performance of check analysis instrument, and/or can shown in 640, use also the analytic set box with help calibration analyte instrument.The blood analysis box can be installed when carrying out blood analysis at every turn.Can produce accurate result with the check analysis instrument with control enclosure regularly as being contained in the analyser for 1 time every day.More low frequency such as will calibrate for per 3 months 1 time box-packed in analyser, with calibration analyte instrument again, perhaps calibration as required.
Every kind of box type all can comprise the composition of all essential fluids and/or performance corresponding function.Like this, can not need a lot of trainings just can operate and/or the maintenance analysis instrument, obtain accurate result.The sample analyser with movable and/or disposable cassette that provides can be through seldom or without professional training just using outside laboratory environment reliably, can help to make the streaming of sample analysis process, minimizing expense and medical worker's burden, increase the convenience of many patient's sample analysis, comprise the patient of blood monitoring/analysis that need be quite frequent.
In the illustrative methods of Figure 12, when using the blood analysis box, control arrives step 604.In step 606, blood sample is provided to disposable fluid box.Control arrives step 608 then, wherein disposable fluid box is inserted in the blood sample analysis instrument.Control arrives step 610 then.Step 610 starts the blood sample analysis instrument, and step 612 obtains analysis result from the blood sample analysis instrument.
When using control enclosure, control arrives step 620.Step 620 causes the control to step 622, wherein control enclosure is inserted in the blood sample analysis instrument.Control arrives step 624 then.Step 624 starts the blood sample analysis instrument, and step 626 is with controlling the controlled analysis result of fluid box.Control arrives step 628 then.Step 628 determines that the control analysis result is whether in the expection range of control.If the control analysis result not in desired extent, should not believe the result that the blood analysis box obtains.In some cases, available calibration box is the calibration sample analyser again, then with the operation/calibration of another control enclosure verification sample analyser.
When using the calibration box, control arrives step 640.Step 640 causes the control to step 642.Step 642 will be calibrated box and be inserted in the blood sample analysis instrument.Control arrives step 644 then.Step 644 starts the blood sample analysis instrument, and step 646 obtains the calibration analyte result with the calibrating fluid box.Control arrives step 648 then.According to the calibration analyte result, step 648 is regulated analyser as required.
In some cases, sample analyser can be full automatic instrument, integral type and/or self-holding testing tool.Sample analyser can receive and analyze direct untreated sample such as capillary blood (thorn finger), vein whole blood, nose swab or urine etc.Perhaps or in addition, sample analyser can only need basic non-technology dependence sample operations, comprises any operation that depollutes.Equally, sample analyser can only need basic non-technology dependence reagent operation, as " mix reagent A and reagent B ", can not need the operator to intervene when analytical procedure.In some cases, sample analyser can comprise or furnish an explanation book (in some cases, when confirming test clinically suitably the time, sample analyser can comprise or provide obtain and transportation is used to the material of confirming that samples tested is used).
Sample analyser can be equipped with quick with reference to the instructions guide.Quick Reference Guide can provide the quick reference of operation sample analyser.During use, the user is can be with reference to Quick Reference Guide when how to operate sample analyser any problem is arranged.
In some cases, Quick Reference Guide can comprise explains image or chart by oneself, and diagram illustrates various operation stepss, is begun to describe until analysis by sample collection sometimes.In an illustrative examples, Quick Reference Guide includes only image or chart, does not comprise word or comprises the minimum word.This can help the user who is not proficient in concrete syntax (as English) to operate sample analyser effectively.In an illustrative examples, Quick Reference Guide can show and/or describe step: take out disposable cassette in packing; Take off the congested cap of box lancet and/or take off the lid (as band) of label, this label is being exposed to air variable color after one period schedule time; Extract blood samples of patients; The blood that extracts is provided to box; With box-packed in instrument; Operation instrument and reception result; Take out box from instrument, throw aside box.This is an example.
The expection tool housing can comprise the pocket of placing Quick Reference Guide etc.During use, the Quick Reference Guide that the user can open pocket carries out reference.Perhaps, available spiral fashion clip etc. is fixed on the sample analyser shell with Quick Reference Guide, and this can allow the user to stir each page of Quick Reference Guide in use.In another illustrative examples, Quick Reference Guide can be fixed on the movable box, perhaps can be printed on the packing of adorning movable box.In also having another illustrative examples, Quick Reference Guide can be printed on the leaflet, leaflet can be attached near on the wall of sample analyser etc.
In some cases, in order further to reduce the danger that produces error result, can provide one or more fault alarms and/or failure safe mechanical hook-up.For example, in an illustrative examples, sample analyser can help to detect the user whether wrong sample type is provided.For example, if set the white blood cell count(WBC) that sample analyser carries out whole blood sample, then whether the sample analyser sample that can help to detect the user and provide is not blood.
In an illustrative examples, sample analyser can be analyzed, if one or more output parameters outside preset range, then sample analyser may not provide the result and/or send error message or error code.For example, if sample analyser is the flow cytometer that is used for whole blood sample is carried out white blood cell count(WBC), to any leucocyte (or a small amount of leucocyte) counting, then sample analyser may not provide the result to sample analyser, in some cases, provide error message or error code.
In some instances, one or more optical measurement can be used for help identifying in the flow channel whether have incorrect fluid, as when the user provides incorrect sample, perhaps when the correct flow channel that reagent do not provided to fluid box.Figure 13 shows a kind of this type of optical measurement.In Figure 13, sample fluid 700 is present in the passage 702 that the conduit wall 704 by for example fluid box limits.In illustrative examples, conduit wall 704 has refractive index " n
w", sample fluid has refractive index " n
s".Light source 706 provides the incident beam that becomes the angle with one of conduit wall 704 (being collimated light beam sometimes).The detecting device of placing 708 is used to detect the light 710 from conduit wall/example interface reflection.The amount that reflexes to the light of detecting device 708 from passage/example interface will depend on conduit wall " n
w" and sample fluid " n
s" relative index of refraction.When required sample fluid 700 is present in the passage 702, can determine required volume reflection or reflected signal.When providing incorrect sample type or incorrect reagent or other incorrect sample fluid to flow channel 700, " the n of incorrect sample fluid
Ic" refractive index can cause detecting device 708 to measure the different reflected signals of light 710.This type of change can show and has incorrect sample fluid in the flow channel 702.Perhaps or in addition, this type of change can show the further feature that has bubble, clot or other unwanted particle or sample fluid.When detection like this, sample analyser may not provide the result, in some cases, may send error message or error code to the user.
Figure 14 shows that another kind can be used for helping to identify the optical measurement that when has incorrect or unwanted fluid in the flow channel.In Figure 14, sample fluid 720 is present in the flow channel 722 that for example conduit wall 724 of fluid box limits.In illustrative examples, conduit wall 724 has refractive index " n
w", sample fluid has refractive index " n
s".Light source 726 provides the incident beam that becomes the angle with one of conduit wall 724 (being collimated light beam sometimes).The detecting device of placing 728 is used to detect the light 730 that passes passage 722 and sample fluid 720.
In this illustrative examples, make passage 722 enough thin, with convenient sample fluid refractive index " n
s" allow within the required range the time optics tunnelling (optical tunneling) to pass passage 722 and sample fluid 720.If sample fluid refractive index " n
s" be lower than required scope, then light will not pass passage 722, but be reflected.If sample fluid refractive index " n
s" be higher than required scope, then light will tend to pass passage 722 and sample fluid 720, so this example may be suitable for detecting refractive index " n most
s" less than the incorrect sample fluid of the refractive index of required sample (as blood).Perhaps or in addition, this illustrative examples can be used to detect the existence of bubble, clot or other unwanted particle or sample fluid further feature as required.When such detection, sample analyser may not provide the result, in some cases, may provide error message or error code.
Figure 15 is that another kind can be used for identifying the illustrative examples that when has incorrect or unwanted fluid in the flow channel of fluid box for example.In this illustrative examples, sample fluid 750 is provided in the flow channel 752 that is limited by conduit wall 754.In illustrative examples, two or more electrodes 760 are provided on one or more conduit walls 754, in some instances, can form two or more electrodes 760 on one or more plastic sheets, it is layered laminate or the fixing fluid circuit that forms fluid box together.Flow channel 752 flow channels 752 interior or on fluid box that two or more electrode assemblings can be extended on the fluid box extend, and are connected with required driving circuit.
In some cases, power supply 758 can provide electronegative potential AC signal (as less than the 10V peak-peak, less than the 5V peak-peak, less than the 3V peak-peak, less than the 1V peak-peak, less than the 0.5V peak-peak or less than the 0.1V peak-peak), causes the electrochemical reaction of sample fluid 750 with restriction electrode 760.Electrochemical reaction can be for example with in the introducing sample fluids 750 such as bubble, and this may not wish to occur in some cases.
Except using above-described resistivity measurement or the substitute is, expection can be used capacitance measurement.In this illustrative examples, can be by the electric capacity between the two or more electrodes of sample 750 measurements.When providing incorrect sample fluid to flow channel 752, the electric capacity the possibility of result of the incorrect sample fluid scope that surpasss the expectation.The electric capacity scope that surpasss the expectation also can be pointed out the further feature that has bubble, clot or other unwanted particle or sample fluid.When such detection, sample analyser may not provide the result, in some cases, may provide error message or error code.
Figure 16 is that another kind can be used for identifying the illustrative examples that when has incorrect or unwanted fluid in the flow channel of fluid box for example.In this illustrative examples, sample fluid 770 is provided in the flow channel 772 that is limited by conduit wall 774.In illustrative examples, provide PH sensor 776 and sample fluid 770 fluid communication.But the PH of PH sensor 776 detection of sample fluid 770 reports signal to controller 780.When providing incorrect sample fluid to flow channel 772, the PH of the incorrect sample fluid scope that can surpass the expectation.The PH level scope that surpasss the expectation also can be pointed out the further feature that has bubble, clot or other unwanted particle or sample 770.When such detection, sample analyser can not provide the result, in some cases, may provide error message or error code.
Figure 17 can be used for identifying when the illustrative examples of one or more bubbles or other unwanted particle appears in sample fluid in the flow channel.In this illustrative examples, sample fluid 800 is present in the flow channel 802 that the conduit wall 804 by for example fluid box limits.Light source 806 provides the incident beam that becomes the angle with one of conduit wall 804 (being collimated light beam sometimes).The detecting device of placing 808 is used for detecting by the bubble that exists in flow channel 802 sample fluids 800 or the light 730 of other unwanted particle scattering.If for example sample fluid 800 is without any bubble, then light does not pass sample fluid with will having scattering, and detecting device 808 will detect less than signal (or low signal).When detecting device 808 is found to be higher than the light scattering signal of a certain threshold value, show that the sample fluid 800 in the flow channel 802 has one or more bubbles or other unwanted particle, sample analyser may not provide the result, in some cases, may provide error message or error code.
Figure 18 can be used for identifying when the illustrative examples of one or more bubbles or other unwanted particle appears in the sample fluid in the flow channel.In this illustrative examples, sample fluid 820 is present in the flow channel 822 that the conduit wall 824 by for example fluid box limits.Ultrasonic transducer 826 and ultrasonic receiver 828 adjacent flow channels 822 are provided.In some cases, the ultrasonic transducer 826 that provides is positioned at flow channel 822 1 sides, and the ultrasonic receiver 828 that provides is positioned at offside.In other cases, ultrasonic transducer 826 that provides and ultrasonic receiver 828 are positioned at flow channel 822 homonymies.In either case, ultrasonic receiver 828 all can be used for detecting the scattering that is caused the ultrasonic signal that ultrasonic transducer 826 sends by the bubble in the fluid sample 820 or other unwanted particle.When such detection, sample analyser may not provide the result, in some cases, may provide error message or error code.
Figure 19 is that another kind can be used for identifying when the illustrative examples of one or more bubbles or other unwanted feature appears in the sample fluid in the flow channel.In this illustrative examples, sample fluid 850 is positioned at the flow channel 852 that the conduit wall 854 by for example fluid box limits.The flow sensor that provides 856 and flow channel 852 fluid communication are used for the flow velocity of detection of sample fluid 850.Flow sensor can be for example hot gas flow velocity type flow sensor and/or microbridge type flow sensor.Microbridge flow sensor for example is described in, U.S. Patent number 4,478,076, U.S. Patent number 4,478,077, U.S. Patent number 4,501, and 144, U.S. Patent number 4,651,564, U.S. Patent number 4,683,159 and U.S. Patent number 5,050,429, all be attached to herein by reference.
Pressure source 860 can offer variable pressure the sample fluid 850 in the flow channel 852.Controller 862 can receive the flow velocity signal from flow sensor 856, in some cases, and may command pressure source 860.In an illustrative examples, for the bubble of detection of sample fluid, controller 862 can cause pressure source 860 flip-floies to be applied to the pressure of sample fluid 850.Utilizable flow sensor 856 is monitored the flow velocity change that sample fluids 850 are produced then.
Figure 20 shows to be provided to the figure of the exemplary pressure pulse 900 of Figure 19 flow channel 852 interior sample fluids 850 by pressure source 860.Seldom or when not having bubble, can obtain 902 flow velocitys that show in the sample fluid 850.When pressure pulse 900 increased suddenly, flow velocity 902 more promptly increased to high flow velocities value 906 from low flow speed value 904, when pressure pulse 900 reduces suddenly, then was reduced to low flow speed value 904 from high flow velocities value 906 rapidly.Yet, when bubble appears in sample fluid 850, when pressure pulse 900 increases suddenly, gained flow velocity 908 (dotted line demonstration) may increase to high flow velocities value 906 from low flow speed value 904 more lenitively, when pressure pulse 900 reduces suddenly, gained flow velocity 908 may be reduced to low flow speed value 904 from high flow velocities value 906 more lenitively.Air in the bubble can for example increase the compressibility of sample fluid 850, so cause flow velocity to increase more lenitively and reduce.The change of flow velocity can be found to have bubble in the sample fluid 850 when exerting pressure change by monitoring.Change fully minimizing if find flow velocity, sample analyser may not provide the result, in some cases, may provide error message or error code.
Expecting pressure source 860 can be suitable pressure source, comprises any other convenient pressure source of conventional pumps, compressed air source or needs.In some cases, pressure source 860 can be high-frequency pressure source such as piezoelectric vibrator, ultrasonic transducer or any other type high-frequency pressure source.In some cases, use can be united with conventional pumps or other pressure source in the high-frequency pressure source, can parallel work-flow.That is to say that when the analytic sample fluid, conventional pumps or other pressure source 860 can be used for making the actual flow channel 852 that moves through fluid box of sample fluid.The high-frequency pressure source cannot be used to make the moving passage of sample fluid longshore current obviously to move, but can be used for sample fluid is produced high-frequency pressure pulse some parameter with detection of sample fluid, comprises the existence of bubble for example, the compressibility of sample fluid etc.The compressibility of sample fluid can be used for helping whether the sample fluid 850 in definite flow channel 852 is expection sample fluid types, if not, then sample analyser may not provide the result, in some cases, may provide error message or error code.
In anything part, in some cases, when high-frequency pressure source and conventional pumps or other pressure source simultaneously or during parallel running, can be when fluid circuit be handled sample the in-situ monitoring sample fluid.
In some cases, pressure pulse can be used for determining or the flow channel in estimating of fluid loop in the position of sample fluid end or far-end.Figure 21 shows a kind of this type of illustrative examples.In Figure 21, show two flow channels 1000 and 1002.Sample fluid 1004 is present in the flow channel 1000, and sample fluid 1006 is present in the flow channel 1002.Show that pressure transducer (as pressure source) 1008 and pressure receiver (as pressure transducer) 1010 are in known location and 1004 mobile connections of sample fluid with respect to flow channel 1000.Pressure transducer 1008 can produce pressure pulse in sample fluid 1004.Pressure pulse is transmitted to terminal 1012 along sample fluid 1004.Some energy of pressure pulse will be by the end 1012 reflected back pressure receivers 1010 of sample fluid 1004.The distance of terminal 1012 current positions and pressure transducer 1008 and/or pressure receiver 1010 and pressure pulse are transmitted to terminal 1012 and the time correlations of returning pressure receiver 1010 needs along sample fluid 1004.Therefore, to terminal 1012 and time of needing of returning pressure receiver 1010, can measure the position of the moving path 10 00 of terminal 1012 longshore currents by the gaging pressure pulse propagation.
Figure 22-23 show to determine the illustrative methods when two kinds of fluids compile at fluid circuit.In many sample analysers, be that different fluid is provided at different flow channels at first.Yet in fluid circuit, various fluids mix usually.For example, though blood sample and modulizer can be provided in the independent flow channel at first, then be mixed in somewhere, fluid circuit downstream.When and how various fluids are concentrated may be very important to the allomeric function of sample analyser, and disclosed as U.S. Patent Application Serial Number 10/932,662, it transfers the assignee of the present invention, is attached to herein by reference.
In order to help to determine when two or more fluids compile in the fluid circuit downstream, and the available pressure transducer produces pressure pulse at least a fluid sample.For example, with reference to Figure 22, pressure transducer 1030 (as pump, piezoelectric vibrator, ultrasonic transducer or any other type pressure transducer) can produce pressure pulse in the sample fluid 1032 in the first mobile path 10 34.Pressure receiver 1036 (as pressure transducer, ultrasonic receiver etc.) can with sample fluid 1040 fluid communication of second flow channel 1042.The first mobile path 10 34 and second flow channel 1042 can concentrate on flow channel 1044, preferably show as Figure 23.
With reference to Figure 22, can propagate along first kind of sample fluid 1032 again by the pressure pulse that pressure transducer 1030 produces in first kind of sample fluid 1032, but may not obvious end or the far-end 1046 that extends to first kind of sample fluid 1032.In illustrative examples, at first fill the flow channel 1044 that Figure 22 shows with air or other gas, then when sample fluid 1032 and 1040 by when its flow channel 1034 and 1042 separately promotes by sample fluid 1032 and 1040 replacements.Before sample fluid 1032 and 1040 was concentrated, pressure receiver 1036 can not receive from the significant pressure pulse of pressure transducer 1030 or the pressure pulse of obviously decaying.
Can start one or more pressure source (not shown)s such as pump etc., sample fluid 1032 and 1040 is moved along its flow channel 1034 and 1042 separately, compile, better show as Figure 23 until sample fluid 1032 and 1040.When this situation occurring, the pressure pulse that pressure transducer 1030 produces can more freely be transmitted to pressure receiver 1036 now.Therefore, when begin to receive or receive pressure pulse, can determine when sample fluid 1032 and 1040 compiles from the less decay of pressure transducer 1030 by monitoring pressure receiver 1036.
In some cases, pressure transducer 1030 can produce pressure pulse sequence (sometimes quite high-frequency) in sample fluid, the pump that can move with the actual flow channel 1034,1042 and 1044 that makes sample fluid 1032 and 1040 longshore current body loops or other pressure source are simultaneously or parallel work-flow.Therefore, pressure transducer 1030 can be used for the sample fluid of in-situ monitoring fluid circuit, more specifically monitors sample fluid 1032 and 1040 and when compiles in the downstream.
In some cases, sample analyser is not in surface level when analyzing, and can influence the operation of sample analyser.In order to detect this situation, the expection sample analyser can comprise horizon sensor.In an illustrative examples, horizon sensor can be the Micro Tilt sensor (D6B) available from Omron Corporation.Other horizon sensor can comprise the ball sensor with electricity output.Usage level sensor, sample analyser can determine whether enough levels are to analyze for sample analyser.If sample analyser does not measure up, then the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.
The another kind of sample for reference analyser whether method of enough levels comprises and makes the one or more flow channel step-down of holding fluid, measures the flow velocity of fluid in one or more flow channel.If sample analyser does not measure up, gravity can cause the flow velocity of the one or more flow channel scope that surpasss the expectation.The scope if flow velocity surpasss the expectation can be considered as sample analyser not measure up, and the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.
In some cases, analysis time collision or mobile example analyser may influence the sample analyser operation.In order to find this situation, the expection sample analyser can comprise vibrations and/or oscillation gauge.In an illustrative examples, vibrations and/or oscillation gauge can be the Shock/Vibration sensors (D7E-2) available from OmronCorporation.Use vibrations and/or oscillation gauge, sample analyser can be determined whether sample analyser is collided or move.If sample analyser is fully collided, then sample analyser may need user operation control card or calibration card before beginning, with the true(-)running of verification sample analyser.Whether sample analyser was collided or is moved when in some cases, sample analyser can be determined to analyze.If sample analyser is fully collided when analyzing, then sample analyser may not provide the result, in some cases, may provide error message or error code.
In some cases, sample analyser can comprise instrument and movable and/or disposable cassette.Because user's behavior can not be expected sometimes, so may confirm box is correctly inserted in the instrument before beginning analysis.A kind of implementation method is box and instruments design to be become to have only in the right directionly just box to be inserted in the instrument.For example, Figure 24 shows the box 1100 that is received (arrow 1104) by the line of rabbet joint of instrument 1102.Exemplary cartridge 1100 comprises the groove 1106 that is positioned at box 1100 upper surfaces.Instrument comprises corresponding male member 1108, and when when inserting box 1100 with respect to instrument 1102 in the right directionly, this male member is fit to extend in the groove 1106.Insert box 1100 if turn upside down, then groove 1106 and male member 1108 are incited somebody to action not counterpart, will prevent that box 1100 from inserting in the line of rabbet joint of instrument 1102 fully.Equally, insert in the line of rabbet joint of instruments 1102 as an end 1112 of compartmentalized box for holding assorted fruits and candies 1100, then groove 1106 and male member 1108 counterpart not will prevent that box 1100 from inserting in the line of rabbet joint of instrument 1102 fully.This just can only be with a kind of example in the correct direction insertion instrument 1102 with Bedpan 1100 with box 1100 locking instruments 1102.
Can confirm the direction of box by any method, when particularly not having the lock-related instrument as compartmentalized box for holding assorted fruits and candies with respect to instrument.For example, in some instances, when box correctly inserted instrument, one or more pressure port can be extended between instrument and box.Instrument can be exerted pressure to one or more pressure port, checks and whether finds required fluid.If the instrument pressure port is not docked with the box pressure port, then can not find required fluid.If do not find required flow rate, then the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.
In another example, box can comprise one or more optical windows or other optical texture.If box is correctly packed in the instrument, instrument can optics be ask and is visited the position that comprises one or more optical windows or other optical texture.If detect less than the expection light reaction, then may there be ground in the right direction mounting box, the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.
In some cases, sample analyser may need one or more reagent to carry out required sample analysis.May need to determine whether to exist correct reagent and reagent whether functional.In an illustrative examples, reagent can be sent in container, this container can comprise bar code or other code of the various parameters of identification reagent.Various parameters can be for example, indentifying substance type, date of manufacture, the reagent term of validity and other parameter.Sample analyser can comprise bar code code reader or other code reader, can read various parameters.Then sample analyser can determine reagent for example whether be required sample analysis correct reagent, whether reagent surpasses specifies the term of validity etc.If reagent is not that the correct reagent or the performance of required analysis is bad, then the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.
In some cases, can be stored in reagent movable and/or disposable cassette on.The disposable cassette 1120 that Figure 25 shows comprises three chamber 1122a, 1122b and 1122c, and each chamber is used to store the required particular agent of analysis that will carry out with box 1120.Showing makes bar code 1124 be attached to box 1120.In case box is correctly inserted in the corresponding instrument, and instrument promptly can read bar code, determine reagent whether be required sample analysis correct reagent, whether reagent surpasses it specifies term of validity etc.
Temperature also can influence the performance of some reagent, in some cases, can provide maximum temperature indicator 1126 and/or minimum temperature indicator 1128.Minimum temperature indicator 1128 can be similar to the freezing indicator available from JPLabs.The freezing indicator that is provided by JPlabs adopts the label form that can be easy to adhere to box or other container.When the temperature of freezing indicator was lower than water below freezing, it produced irreversible color change, as the blueness look that reddens.Instrument can comprise the optics inquiry spy device that detects freezing indicator 1128 colors, if reagent has been exposed to the temperature that is lower than minimum temperature, then the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.
Equally, maximum temperature indicator 1126 can be similar to the temperature indicator available from JP Labs.When reaching certain predetermined temperature (or temperature range, usually above room temperature), color change appears in these indicator.When heating, they from colourlessly become redness, from colourlessly becoming green, becoming redness etc. from blueness.Can be easy to these indicator are added in the printing ink instrument such as relief printing plate (flexo) and intaglio plate (gravure) of commercially available acquisition.Instrument can comprise the optics inquiry spy device of detected temperatures indicator 1126 colors, if reagent has been exposed to the temperature that is higher than maximum temperature, then the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.
Humidity and/or moisture indicator also can be provided.Humidity and/or moisture indicator can be similar to available from those of JP Labs.All be exposed to after the moisture humidity and/or moisture indicator color change can take place.Under home humidity, the time that color change needs can not waited from a few minutes to several weeks.
Instrument can comprise the optics inquiry spy device of indicator 1130 colors detection time, if the time period arrives after date, the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.This can be the user and specifies the schedule time open the box packing, blood or other sample are contained in box 1120 and analyze with instrument.This can help to reduce the user thereby sample is contained in box 1120, waits for the chance that allows sample solidify, to become dry too for a long time or change feature then before analyzing.
When packing is taken out box 1120, not start-up time indicator, but a band 1132 or other material are provided on the sample input port 1134 of box 1120.An available band 1132 or other material cover on time marker 1136.Sample is packed into before the box, and the user must remove band 1132 or other material, make then time marker be exposed to environment and start-up time indicator.Through behind the predetermined amount of time, time marker 1136 changeable colours or detectable condition is provided.
Instrument can comprise the optics inquiry spy device of indicator 1136 colors detection time, if time is up, the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.This can be the user and specifies the schedule time of removing band 1132 or other material from the sample input port, blood or other sample being contained in box 1120 and analyzing with instrument.This can help to reduce the user thereby sample is contained in box 1120, waits for the chance that allows sample solidify, to become dry too for a long time or change feature then before analyzing.
In some cases, box can comprise that help is with the spring driving lancet of blood sample collection in box.For example, Figure 26 shows the exemplary cartridge 1150 that comprises spring driving lancet 1152.Spring driving lancet 1152 can comprise spring or other biased element 1153 that makes lancet deflection extension bit 1154.Release mechanism 1156 is connected lancet is locked in punctured bit 1158 with spring driving lancet 1152.When the user starts release-push or handle 1160, but release mechanism 1156 retracting spring driving lancets 1152, and lancet can move to extension bit 1154 from punctured bit 1158 suddenly.If user's finger withstands box 1150 when starting release-push or handle 1160, then spring driving lancet 1152 can pierce through user's skin, sucking-off appropriate amount blood.Spring driving lancet 1152 can with the sample collection kapillary (not shown) fluid communication in the box 1150, therefore in some instances, blood sample directly can be delivered in the sample collection kapillary of box 1150.Spring driving lancet 1152, release mechanism 1156 and release-push or handle 1160 can be similar to available from Becton, the BD of Dickinson and Company
TMLancet Device.
Perhaps, sample can be delivered in the sample input or kapillary of box through transfer pipet (may use the anti-coagulants coating) from the finger that for example pierces through.Available syringe is with in sample transfer and the introducing box.Thorn, cut or cut finger before available alcohol swab sheet wiping finger prepare.Can use the lancet that is carved with set depth, as the lancet 1152 of box among Figure 26 1150.
In some cases, with reference to Figure 27, movable and/or disposable cassette 1200 can comprise the mechanical hook-up of removing bubble in the fluid.In some cases, when bubble under the perforated membrane that forms the part flow channel wall through out-of-date, can remove the bubble in the liquid stream in the flow channel.In Figure 27, show that the moving passage 1170 of the positive longshore current of alveolate liquid flows.Film 1172 separates flow channel 1170 and draft chamber 1174.The pressure of draft chamber 1174 keeps below the pressure of flow channel 1170.In some cases, film is a hydrophobic membrane, as available from Millipore Corporation, and Billerica, the Fluoropore of Mass
TM, Mitex
TMOr Durapore
TMFilm.Mitex
TMFilm prepares with PTFE, and the aperture is 5 or 10 microns.Fluoropore
TMFilm prepares with the PTFE with HDPE carrier, and the aperture is 1 or 3 micron.Durapore
TMFilm prepares with Kynoar, and the aperture is 0.1,0.22 and 0.45 micron.Hydrophobic membrane can be kept the elevated pressures difference usually and fluid be leaked by water transfer membrane.
Pressure differential between flow channel 1170 and the draft chamber 1174 forces the gas of bubble 1180 to pass film 1172 and outer exhausr port 1182, causes the bubble in film 1172 downstream liquids obviously to reduce (preferably not having bubble).Bubble-free then liquid can as 1184 demonstrations, further be handled by the fluid circuit on movable and/or the disposable cassette to dirty.
Though in order to obtain the identical gas flow rate from the bubble 1180 of catching, the smaller aperture of larger aperture needs littler pressure differential, larger aperture can not both be kept big pressure differential and don't allow liquid to pass through.The film of estimating to have 1 micron hole should be kept the pressure differential of 1PSI, depends on the surface energy and the pore geometry feature of liquid and film.
Figure 28 is the illustrative examples synoptic diagram of bubble grabber 1191 on flow channel 1185 sidewalls.Bubble 1187 can move in one or more grabbers 1191 along fluid 1193, with 1189 gatherings of the bubble in grabber and fusion; Perhaps bubble 1191 becomes the initial bubble 1189 in the grabber.Grabber can be out of shape in flow channel wall as the triangle hook-type, when bubble by the time can be trapped and can not flow back in the fluid from grabber.Except the triangle that shows, the grabber shape can also be rectangle, semisphere etc.
In some instances, sample analyser can have the electronic equipment and/or the software of each parts of control sample analyser.In some cases, though sample analyser can be powered by line voltage distribution, under powering-off state, can have backup battery.Electronic equipment also can comprise clock chip (having backup battery sometimes), to keep correct time and date.Correct time and date for example can be used for relatively the reagent term of validity that can read from the bar code on reagent packing or the box etc., to determine whether reagent still can use.
If the result is not sent in outage when analyzing, and backup battery is not provided, but then electronic equipment and/or software termination analysis, in some cases, send error message or error code to the user.
Electronic equipment and/or software can be connected with detecting device with the various light sources of sample analyser.In some instances, electronic equipment and/or software can be before sample analysis, afterwards and/or regularly or the omnidistance operation of checking light source and photodetector.For example, electronic equipment and/or software can be before sample analysis, afterwards and/or regularly or the one or more detecting devices of omnidistance checking whether detecting the light that respective sources provides.
Perhaps or in addition, can after box inserts instrument but before routine analyzer begins, identify the scrambling (irregularities) of box, as the crack of optical window or the dust or the chip of optical window.This can make light pass optical window and finishing with one or more detecting device detection optical features (reflection, scattering, FALS, SALS, LALS etc.) by for example starting one or more light sources.If optical window comprises crack, dust or chip on optical window or other atypical characteristic arranged, then these atypical characteristics can be in the optical signature that produces on the detecting device outside the expection.If this type of atypical characteristic of electronic equipment and/or software discovery, then the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.Available cotton sheet cleans sordid optical device.
If there is flow sensor in the sample analyser, then a certain electronic equipment and/or software can be before analyzing, afterwards or monitoring stream quantity sensor output when analyzing, with the flow velocity of proof prompting within the required range or meet required distribution plan.If the flow velocity of electronic equipment and/or software discovery prompting is not within the required range or do not meet required distribution plan, then the result not analyzed and/or do not provided to sample analyser may, in some cases, may provide error message or error code.
In some cases, sample analyser can comprise certain built-in self-test (BIST) level.For example, under test pattern, some or all storage element (as register) in electronic equipment selectivity together can be connected in the serial scan chain, wherein can be in the chain type register with test vector continuous sweep.In some cases, the input and output of electronic equipment can comprise the scratchpad register that only logic is inserted in test pattern.Can begin the functional clock period, wherein test vector bit (bits) be discharged by the logical circuit (logic) between the register, obtain the result by register.The result can be gone out register by continuous sweep then, compares with expected results.But the electronic equipment of this full test sample analyser.
Can implement many these type of test vectors to realize required fault coverage.In some cases, fault coverage can be as required greater than 50% logical circuit, greater than 60% logical circuit, greater than 80% logical circuit, greater than 90% logical circuit, greater than 95% logical circuit or greater than 99% logical circuit.In case after the test, electronic equipment can be gone back to functional mode, can restart the normal function operation of sample analyser.Sample analyser can regular intervals of time as per hour 1 time, every day 1 time, 1 time, every month 1 time or enter test pattern automatically with any other required interval as required weekly.
In some cases, according to purposes, with electronic equipment and/or software design and/or test, provide the mean time between failures (MTBF) for greater than 5,000 hours, greater than 8,000 hours, greater than 10,000 hour, greater than 50,000 hours, greater than 100,000 hours or more than.
In some instances, can be with sample analyser by Internet connection to a remote place or many places.When providing like this, test result can be delivered to and far be used for long term storage and/or further analyze (if desired).In addition, expection far can comprise and can carry out the remote diagnosis of sample analyser and/or the diagnostic software of maintenance.In some cases, but the far hardware of auto-update sample analyser or software.
Card Rejections and other mistake can be sent to far.Can determine far whether concrete sample analyser unusual high mistake occurs.Unusual high mistake can point out sample analyser to have inefficacy or marginality (marginal) hardware component, far can send the maintenance personal to keep in repair/change these parts before the user pinpoints the problems.The user that also can point out in this position in the unusual high mistake of particular location may need more trainings.This type of training can be from far being dispatched into lab assistant.Can becoming box not with instruments design, trainee person also can operate.
Far also but statistical study is identified sample analyser parts, software or other zone that can strengthen from the mistake and/or the BIST result of a plurality of sample analysers in the sample analyser later release.
As required, can be with in the sample analyser or temperature on every side, humidity and other environmental parameter, and impact, tilt and other sensing data regularly detects and is sent to far.
In this manual, certain situation can be supposition or prophesy character, but in another way or tense statement.
Though describe the present invention about at least one illustrative examples, those skilled in the art will know many changes and modification after reading this instructions.Therefore the appended claims of explaining with prior art as far as possible widely are intended to comprise all this type of change and modifications.
Claims (49)
1. sample analyser, described sample analyser comprises:
Instrument with line of rabbet joint; With
Be used to insert the box of the line of rabbet joint;
When box inserts the line of rabbet joint near the light source of box; With
When box inserts the line of rabbet joint near the detecting device of box; And
Wherein:
Flow channel comprises conduit wall;
Conduit wall has first refractive index;
Sample fluid in the flow channel has second refractive index; And
Light source is used for illumination is gone into to flow in the passage.
2. the analyser of claim 1, wherein:
Detecting device is used to detect the light of first and second refractive index interfaces reflection;
The light indication fluid refracting rate that detecting device detects; With
If the fluid refracting rate is not in specified scope, then sample analyser can not analyzed, do not provided result, the incorrect fluid of indication and/or error flag is provided.
3. the analyser of claim 1, wherein conduit wall is enough thin, so that the δ between first and second refractive index allows the optics tunnelling when being within the satisfactory scope of fluid.
4. the analyser of claim 1, if wherein the fluid refracting rate is not in specified scope, then fluid may be incorrect sample or sample, has incorrect reagent, bubble, clot and/or pollutant etc.
5. the analyser of claim 1, wherein:
Detecting device is used to detect by conduit wall and fluid and passes the outer light of conduit wall arrival passage;
Arrive the refractive index of the light indication fluid of detecting device; And
If the refractive index of fluid is not in the specified scope of appropriate samples fluid, then sample analyser may not analyzed, do not provided result, the incorrect sample fluid of indication and/or error flag is provided.
6. sample analyser, described sample analyser comprises:
Instrument with the line of rabbet joint, the energy and detecting device; With
Box with at least one flow channel, described box is used to insert in the line of rabbet joint.
7. the analyser of claim 6, wherein:
The energy is used to provide light, becomes the angle to pass through flow channel with the wall of flow channel;
Detecting device is used to detect the scattered light intensity from flow channel;
There are unwanted particle or bubble in the fluid of the intensity indication flow channel of a certain scope;
If detect the intensity of a certain scope, then analyser can not provide the result maybe can provide error flag.
8. the analyser of claim 6, wherein:
The energy is ultrasonic transducer, near flow channel, is used for the ultrasonic flow channel that imports into;
Detecting device is a ultrasonic receiver, near flow channel, is used to receive the reflected ultrasound energy from flow channel;
Have in the reflected ultrasound energy indication flow channel of a certain scope intensity and have bubble or other unwanted particle;
If ultrasonic receiver receives the reflected ultrasound energy of a certain scope intensity, then analyser will not provide the result and/or error flag will be provided.
9. the analyser of claim 6, wherein:
The energy is that a certain pressure is changed the pressure source that puts on sample fluid in the flow channel;
Detecting device is the flow sensor that is arranged in flow channel, is used for monitoring the flow velocity of flow channel;
Flow sensor monitoring sample fluid flow velocity, and pressure source changes a certain pressure the fluid that puts in the flow channel;
The compressibility of the change in flow indication sample fluid of the time per unit for a certain pressure changes; And
There is bubble in the compressible amount indication sample fluid of specified scope.
10. the analyser of claim 9, wherein pressure source is high-frequency impulse piezoresistive pressure source.
11. the analyser of claim 9, if there is bubble in the sample fluid in the indication flow channel, then analyser will not provide the result and/or error flag will be provided.
12. the analyser of claim 6, wherein:
The energy is the pressure transducer that transmits pressure pulse in the sample fluid of flow channel, is positioned at the primary importance of the moving passage of longshore current with respect to the sample fluid end;
Detecting device is the pressure receiver that receives the pressure pulse of fluid end reflection, is positioned at the second place of the moving passage of longshore current; And
The moving passage of longshore current transmits pressure pulse to the duration that receives between the reflected impulse and indicates described end along the position of flow channel with respect to first and second positions.
13. the analyser of claim 6, wherein:
The energy is the pressure transducer that transmits pressure pulse in the sample fluid of flow channel, is positioned at the primary importance of the moving passage of longshore current with respect to the sample fluid end;
Detecting device is the pressure receiver that receives the pressure pulse of fluid end reflection, is positioned at the second place of the moving passage of longshore current; And
The moving passage of longshore current transmits pressure pulse to the duration that receives between the reflected impulse and indicates described end along the position of flow channel with respect to first and second positions.
14. the analyser of claim 6, wherein:
The energy is the pressure transducer that transmits pressure pulse in the first fluid of first flow channel;
Detecting device is the pressure receiver that receives from the pressure pulse of second fluid in second flow channel;
Have terminal first fluid and be positioned at first flow channel;
Have the second terminal fluid and be positioned at second flow channel; And
If pressure pulse is produced in first fluid by pressure transducer, then the end one of first and second fluid is joined, and pressure receiver just tangible pressure pulse signal will occur.
15. a sample analyser, described sample analyser comprises:
Instrument with line of rabbet joint;
Be used to insert the box of the line of rabbet joint; With
The horizon sensor that connects analyser; And
If wherein horizon sensor indication analyser does not measure up, then analyser may not analyzed, do not provided the result and/or error flag will be provided.
16. a sample analyser, described sample analyser comprises:
Instrument with line of rabbet joint;
Be used to insert the box with one or more flow channels of the line of rabbet joint;
Lay respectively at the one or more flow sensors in one or more flow channels;
If the flow velocity of one or more flow sensor indications exceeds the flow velocity desired extent, then analyser can be considered to not measure up, and then analyser may not analyzed, do not provided the result and/or error flag will be provided.
17. a sample analyser, described sample analyser comprises:
Instrument with line of rabbet joint;
Be used to insert the box with one or more flow channels of the line of rabbet joint;
Lay respectively at the one or more flow sensors in one or more flow channels;
If the flow velocity of one or more flow sensor indications exceeds the flow velocity desired extent, fluid in then one or more flow channels can be considered to incorrect, then the result may not analyzed, do not provided to analyser, can indicate incorrect fluid, and/or error flag will be provided.
18. a sample analyser, described sample analyser comprises:
Instrument with line of rabbet joint;
Be used to insert the box with at least one flow channel of the line of rabbet joint;
Wherein:
Instrument has the first structure accessory;
Jig has the second structure accessory that matches with the first structure accessory;
First and second structure accessory can only insert card in correct direction.
19. a sample analyser, described sample analyser comprises:
Instrument with fluid flow port; With
Can insert the card of instrument; And
Wherein:
The jig that inserts instrument with correct direction has aligning and the fluid flow port that is connected the instrument flow mouth;
The fluid flow port of instrument has the flow sensor of measuring respectively by the flow of fluid flow port;
If flow sensor has not indicated desired flow to pass through fluid flow port, then Ka one or more fluid flow ports do not have to aim at and the fluid flow port that is connected instrument, show that card may insert in the instrument with incorrect direction, the result may not analyzed, do not provided to analyser, and/or error flag will be provided.
20. a sample analyser, described sample analyser comprises:
Instrument with one or more optical windows;
Have the card of one or more optical windows towards one or more passages or approach, described card can insert in the instrument;
The jig that inserts instrument with correct direction has one or more windows, one or more windows of described window optics aligner device;
If do not occur the optical communication of expecting between one or more windows of card and the one or more windows of instrument, then the result may not analyzed, do not provided to sample analyser, and/or error flag will be provided.
21. a sample analyser, described sample analyser comprises:
Instrument with socket of band code reader; With
Parts with inserted socket of label.
22. the analyser of claim 21, wherein:
Parts are reagent containers;
Label is the code of indication reagent container content parameter;
If reagent container is placed socket, then the code on the reagent container can be read by code reader, to determine the parameter correctness;
If one or multiple parameters are incorrect, then the result may not analyzed, do not provided to sample analyser, will indicate incorrect reagent, and/or error flag will be provided.
23. the analyser of claim 21, wherein:
Parts are boxes;
Label is the bar code that comprises parameter, timing, input pressure, flow velocity, software and/or the software upgrading etc. of the analysis type that described parameter such as box ID, box are supported, box calibration parameter, box operation;
If it is compatible with instrument that code reader is pointed out parameter, then sample analyser can be analyzed;
If it is incompatible with instrument that code reader is pointed out parameter, then sample analyser may not analyzed, and the result is not provided, and/or error flag will be provided.
24. the analyser of claim 21, wherein:
Parts are boxes;
Box has reagent going along with;
Label is the bar code that comprises every kind of reagent information going along with, described information indication type, build date and data, the term of validity and/or other parameter;
If it is incompatible with instrument that code reader is pointed out the information of box bar code, then sample analyser may not analyzed, and the result is not provided, and/or error flag will be provided.
25. the analyser of claim 21, wherein:
Parts are boxes;
Label is the RFID label;
The RFID label comprises following information: timing parameters, input pressure, flow velocity, software and/or the software upgrading etc. of the analysis type that box ID, box are supported, box calibration parameter, operating case;
If it is compatible with instrument that code reader is pointed out information, then sample analyser can be analyzed;
If it is incompatible with instrument that code reader is pointed out information, then sample analyser may not analyzed, and the result is not provided, and/or error flag will be provided.
26. the analyser of claim 21, wherein:
Parts are boxes;
Label is the RFID label;
Box has reagent going along with;
Type, build date and data, the term of validity and/or other parameter of every kind of reagent going along with of RFID label indication;
If it is incorrect or incompatible with instrument that code reader is pointed out the information of box RFID label, then sample analyser may not analyzed, and the result is not provided, and/or error flag will be provided.
27. the analyser of claim 21, wherein:
Parts are boxes;
Label is humidity/moisture indicator, time marker and/or the highest and/or minimum temperature indicator;
Code reader is that optics is ask the spy device;
Humidity/moisture indicator generation change color is ask the spy device for optics and is read;
Time marker generation change color is ask the spy device for optics and is read;
The highest and/or minimum temperature indicator generation change color is ask the spy device for optics and is read.
28. the analyser of claim 27, if wherein optics ask to visit device read the highest and/or minimum temperature detecting device, humidity/moisture indicator and/or time marker gained result unacceptable, then sample analyser may not analyzed, and the result is not provided, and/or error flag will be provided.
29. the analyser of claim 28, if wherein optics ask to visit device read the highest and/or minimum temperature detecting device, humidity/moisture indicator and/or time marker gained result unacceptable, then reagent and/or fluid sample addle or are incorrect.
30. a sample analyser, described sample analyser comprises:
Before analyzing operation, simultaneously and/or the built-in self-test of testing scanning chain is provided afterwards; And
Test comprises may command and observable pattern in the loop.
31. a sample analyser, described sample analyser comprises:
Instrument with one or more windows; With
Box with one or more windows of one or more windows of aiming at instrument respectively, described box can insert in the instrument; And
Wherein before analyzing operation, check crack, dust or other chip on one or more windows with light scattering, reflection and/or transmission measurement.
32. the analyser of claim 31, if wherein light scattering, reflection and/or transmission measurement result are considered to unsatisfactory, then sample analyser may not analyzed, and the result is not provided, and/or error flag will be provided.
33. a sample analyser, described sample analyser comprises:
Instrument;
Box with one or more flow channels;
Wherein:
It is coupled that one or more flow channels have at least one flow sensor separately,
Before analyzing operation, simultaneously and/or monitor each flow sensor output afterwards;
Check that the output of each flow sensor is to determine that it is whether in desired extent and/or flow distribution figure;
If a flow sensor output is regarded as not in desired extent and/or profile of flowrate, then sample analyser may not analyzed, and the result is not provided, and/or error flag will be provided.
34. a sample analyser, described sample analyser comprises:
Instrument;
Can insert the box of instrument;
Wherein:
Instrument comprises:
The input of AC power; With
Backup battery power.
35. a sample analyser, described sample analyser comprises:
Instrument;
Can insert the box of instrument;
Before analyzing operation, simultaneously and/or the hardware of self check afterwards; With
Before analyzing operation, simultaneously and/or the software of self check afterwards.
36. a sample analyser, described sample analyser comprises:
Instrument;
Can insert the box of instrument; With
Connect the internet/network communication contact of instrument; And
Wherein internet/network communication contact comprises:
The result who analyzes operation is delivered to remote location;
The software of position upgrade analysis instrument from afar; And/or
The information of box refusal is offered remote location.
37. the analyser of claim 36, wherein internet/network communication contact provides the service of sending with charge free to have the problem of high error rate and/or the wrong analyser of identifying with correction.
38. the analyser of claim 36, wherein the result of comprehensive a plurality of sample analysers is got in touch in internet/network communication, to determine FAQs and/or for the correction of hardware and/or software.
39. the analyser of claim 36, wherein the contact of internet/network communication termly, exceed when specifying limit value as required or in environmental parameter, to environmental parameter far is provided.
40. the analyser of claim 39, wherein environmental parameter comprises that temperature, humidity, collision, inclination, power fail, analyser use and/or other data.
41. a sample analyser, described sample analyser comprises:
Instrument;
Can insert the box of instrument; With
Connect the radio communication contact of instrument; And
Wherein the radio communication contact comprises:
To analyze operation result and be delivered to remote location;
The software of position upgrade analysis instrument from afar; And/or
Box refusal information is provided to remote location.
42. the analyser of claim 41, wherein wireless communication connection comprises the scheme that meets the relevant common acceptable standard of wireless community.
43. the analyser of claim 41, wherein wireless communication connection provides the service of sending with charge free, to correct the problem of high error rate and/or the wrong analyser of verifying.
44. the analyser of claim 41, wherein the result of the comprehensive a plurality of sample analysers of wireless communication connection is to determine FAQs and/or for the correction of hardware and/or software.
45. a sample analyser, described sample analyser comprises:
Instrument with line of rabbet joint; With
Be used to insert the box with flow channel of the line of rabbet joint; And
Wherein:
Flow channel has flow sensor;
If have the passage step-down of fluid, flow sensor can be measured the rate of flow of fluid that the gravity level causes;
The level of flow velocity indication analyser;
If the analyser level is not in specified scope, then analyser may not analyzed, and the result is not provided, and/or error flag will be provided.
46. a sample analyser, described sample analyser comprises:
Instrument;
Can insert the box of instrument; With
Vibrations/the oscillation gauge that connects instrument; And
Wherein:
Can be before analyzing, simultaneously and/or afterwards by sensor vibrations/swing;
Operate acceptable specified intensity if vibrations/swing surpasses analyser, then analyser may not analyzed, and the result is not provided, and/or error flag will be provided.
47. a sample analyser, described sample analyser comprises:
Instrument;
Can insert the box of instrument; With
At at least one interface between fluid pool and passage on the box; And
Wherein:
The interface comprises:
Barrier film on the passage; With
The hollow needle that connects storage pool; And
Pin is used to pierce through barrier film, and fluid is transported to passage from storage pool, and withdraws from from barrier film, allows barrier film closed voluntarily, because puncture does not occupy the barrier film core.
48. a sample analyser, described sample analyser comprises:
Instrument;
Can insert the box of instrument;
Be positioned at the storage pool of box;
Film as the storage pool outer wall; With
When inserting instrument, box is positioned at the axle of instrument near film; And
Will move fluid by the box storage pool when wherein inserting as compartmentalized box for holding assorted fruits and candies, then axle is removable contacts with film, pushes film, with the fluid of mobile storage pool.
49. a sample analyser, described sample analyser comprises:
Instrument;
Can insert the box of instrument;
Be positioned at the storage pool of box;
First film for the storage pool outer wall; With
Be positioned at second film on driver one end, described driver is arranged in instrument and close first film when box inserts instrument; And
If wherein fluid is pumped into described driver one end, when then inserting box, second film is out of shape against first film, thereby is moved into towards the storage pool of box, and pushes first film, thereby moves fluid by storage pool.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75329305P | 2005-12-22 | 2005-12-22 | |
| US60/753,293 | 2005-12-22 | ||
| US75501405P | 2005-12-29 | 2005-12-29 | |
| US60/755,014 | 2005-12-29 | ||
| PCT/US2006/048846 WO2007075919A2 (en) | 2005-12-22 | 2006-12-22 | Portable sample analyzer system |
| US11/615,874 US8323564B2 (en) | 2004-05-14 | 2006-12-22 | Portable sample analyzer system |
| US11/615,874 | 2006-12-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101379386A true CN101379386A (en) | 2009-03-04 |
| CN101379386B CN101379386B (en) | 2013-09-25 |
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| CN201711011147.0A Pending CN107894512A (en) | 2005-12-22 | 2006-12-22 | Portable sample analyzer cartridge |
| CN200680053149XA Active CN101379386B (en) | 2005-12-22 | 2006-12-22 | Portable sample analyzer system |
| CNA2006800530923A Pending CN101379385A (en) | 2005-12-22 | 2006-12-22 | Portable sample analyzer cartridge |
| CNA2006800531108A Pending CN101379404A (en) | 2005-12-22 | 2006-12-22 | Haematology analyzer system with mobile case |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711011147.0A Pending CN107894512A (en) | 2005-12-22 | 2006-12-22 | Portable sample analyzer cartridge |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2006800530923A Pending CN101379385A (en) | 2005-12-22 | 2006-12-22 | Portable sample analyzer cartridge |
| CNA2006800531108A Pending CN101379404A (en) | 2005-12-22 | 2006-12-22 | Haematology analyzer system with mobile case |
Country Status (1)
| Country | Link |
|---|---|
| CN (4) | CN107894512A (en) |
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| Publication number | Publication date |
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| CN107894512A (en) | 2018-04-10 |
| CN101379404A (en) | 2009-03-04 |
| CN101379385A (en) | 2009-03-04 |
| CN101379386B (en) | 2013-09-25 |
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