CN1786710B - Microfluid chip for testing analysing body and its method - Google Patents
Microfluid chip for testing analysing body and its method Download PDFInfo
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- CN1786710B CN1786710B CN 200410096915 CN200410096915A CN1786710B CN 1786710 B CN1786710 B CN 1786710B CN 200410096915 CN200410096915 CN 200410096915 CN 200410096915 A CN200410096915 A CN 200410096915A CN 1786710 B CN1786710 B CN 1786710B
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Abstract
The present invention discloses measuring body analysis micro flow body chip and its method. It is mainly utilized slightness micro flow passage on chip as measured matter content analysis area to make the measured matter react with complex number fixed substance in micro flow passage, and adjust the reaction to make reaction start point of the analysis area to cumulate orderly to reach reaction range concentration effect through a reaction adjusting part. The reaction adjusting part is the micro flow passage which comprises an upper and a lower substrates respectively made by hydrophilia or hydrophobic material. Chip user can refer to micro flow passage appearance and exterior graduation to know measured matter content according to the size of the reaction range in micro flow passage.
Description
Technical field
The present invention relates to a kind of micro-fluid chip and method thereof that can be used for determinand content analysis in the corpse or other object for laboratory examination and chemical testing, mainly utilize on the chip elongated fluid channel as determinand content analysis district, the interior plurality of fixed material of intravital determinand of inspection and aforementioned fluid channel is reacted, and the touch opportunity of regulating determinand and fixed substance in the corpse or other object for laboratory examination and chemical testing by the reaction adjusting portion, make from initial the lighting of the reaction in determinand content analysis district and accumulate reaction in regular turn, reach the effect that reaction range is concentrated.The chip user can be by aitiogenic range size in the aforementioned fluid channel, with reference to the resemblance of fluid channel or outside scale and learn the content of determinand.
Background technology
Many clinical biochemicals detect uses the detecting that all is conceived to specific biochemical substances or pathogenic agent, can reflect ill degree, patient's the healthy state or the curative effect of pharmaceutical treatment by the result who detects.In addition, the detecting of biological or chemical material also can be used for the application such as detection of drug testing, industrial process monitoring, environmental monitoring, plant or animal.The corpse or other object for laboratory examination and chemical testing of biochemistry detection is selected to decide on demand, can be from the sample in human or animal's body fluid such as blood, urine, saliva or serum, processing procedure or the environment etc.Determinand (analytes) then is the pathogenic agent that is contained in the intravital chemical substance of aforementioned inspection, protein, victory peptide, part, nucleic acid or virus, bacterium and so on.
The determinand content analysis can be divided into two kinds, and a kind of is qualitative test (qualitative test), and another kind of is sxemiquantitative/quantitative analysis (quantitative assay).Whether the principle of qualitative test is to detect the target determinand and exists or reach a certain threshold value, gives the result of a positive (positive) or negative (negative) then.A simple example is exactly the pregnant test piece of testing that can buy on the market, hCG in the test subject urine corpse or other object for laboratory examination and chemical testing (human chorionic gonadotropin, the hCG) whether content surpasses a threshold value, for example: 25mIU/ml, if surpass this content, the result who then tests pregnant test piece is with regard to positive result.This kind utilizes the mode of traditional test piece variable color, the experimenter can be sampled voluntarily carry out the house detection, though this method is rapidly convenient, yet can only be used for qualitative detection after all.Of the present inventionly focus on developing a method and the instrument that to do qualitative, sxemiquantitative or quantitative analysis, and be not limited to the level of qualitative analysis.
Distinguish biochemical determinand content analysis with reaction principle, exercisable principle comprises: spectrography (spectrometry), electroanalytical chemistry method (Electroanalytical chemistry), chromatographic separation method (chromatographic separation), electrophoretic method (electromigration methods) and immunoassay (immunoassay) etc.The method of some biochemical analysis needs determinand is indicated and could quantitatively be quantitative person as if doing to distinguish can be divided into again with fluorescent (fluorescence), cold light, ferment (enzyme), radioactivity (radioactive) element, nanoparticle (nanoparticles), magnetic particle modes such as (magneticbead) with marker method.The biochemistry detection instrument that no matter is to use above-mentioned which kind of principle to develop, most detection method all has a common demand, must possess the instrument that has to measure the determinand signal exactly, for example use photometer (photometers) to measure the absorb light of specific wavelength, or use photomultiplier to measure the fluorescence intensity of emitting, or use electrode and voltage or current measurement instrument to measure the small electric signal of reaction back gained, or measure the change amount etc. of color with scanner or CCD camera.
The instant biochemistry detection equipment of Portable can be in the point of care of Branch Clinic, hospital, house or the remote districts that lack medical resource detect, and can obtain detected result immediately.The instant biochemistry detection equipment of Portable possesses following characteristic: the board that (a) does not need to use costliness, heaviness, (b) the simple and easy and operating method of automatization need also can not obtain result accurately and reliably through special training, (c) uses low-cost part, instant losing is to avoid pollution.
The employed equipment of biochemistry detection has the hand held board of the employed large-scale board of large hospital or inspection center, individual's use or simply detects test piece etc. at present.Though it is the instrument price of hand held is lower and be easy to carry about with one, more common with the measurement of several determinands such as blood sugar, uric acid or total cholesterol.If want broadened application to comprising LDL various different types of determinands such as (low density cholesterol Low density lipoprotein), then since in the corpse or other object for laboratory examination and chemical testing existence of other composition be that the detection principle of optical profile type or electric chemical formula all still faces bottleneck and need overcome to the interference of signal no matter make.Therefore, be used in the sxemiquantitative/quantitative analysis in addition of blood sugar, uric acid or total cholesterol at present on the market, use large-scale detecting instrument usually.The large-scale board of this class is subject to hospital more or carry out the inspection center, is unsuitable for the instant biochemistry detection of Portable.Though simple detection test piece price is low, the accuracy that detects determinand content is relatively poor, is applicable to qualitative but not sxemiquantitative/detection by quantitative, and the kind that can detect determinand is just restricted.
In recent years, gradually many with chip as the research of analysis tool, diffraction sensing (diffraction-based sensing) for example, the little balance of quartz crystal (Quartz CrystalMicrobalance), surface plasma resonant (Surface plasmon resonance) etc., these method common characteristics are must design and produce on chip the mechanism relevant with analysis principle, also must arrange in pairs or groups and can be used for making the expensive instrument of determinand content, the user also must have professional operation skill, therefore some method even must add complicated corpse or other object for laboratory examination and chemical testing pre-treatment flow process is unsuitable for the instant biochemistry detection of Portable.
Micro-fluid chip is owing to have the function that can handle micro fluid, and its development is gradually paid attention to, and for example utilizes the electrocapillary phoresis chip to detect the composition in the corpse or other object for laboratory examination and chemical testing.But the electrocapillary phoresis chip must measure with auxiliary its signal of board beyond chip in addition, just can reach quantitative function.Other is not the micro-fluid chip of principle with the electrocapillary phoresis, though also might be used for biochemical analysis, also can't directly finish the quantitative work of determinand by chip.For example No. the 2002/0127740th, U.S. Patent Publication, its method for the corpse or other object for laboratory examination and chemical testing that imports designated volume in reaction zone, as for the content of the determinand measurement mechanism on the chipless then, must add optical detecting instrument and read the result.
Though biochemistry detection test piece price is low, be applicable to qualitative but not detection by quantitative.The pregnant test piece principle of testing of for example aforementioned detection hCG is transverse flow (lateral flow), inhales the test paper that draws liquid (wicking) effect to have, and allows biochemical reaction carry out on test paper.Since simple in structure, the reaction design parameter can be controlled seldom, be fit to do qualitative measurement, then accuracy is not enough if be used for sxemiquantitative/quantitative analysis.United States Patent (USP) the 5th, 559, No. 041 immunodetection test piece, or other utilizes the biochemistry detection test piece of the auxiliary color developing effect of nanometer gold particulate etc., promptly is the example that the biochemistry detection test piece is applied to qualitative analysis.
The research of Se-Hwan Paek, and No. the 5th, 340,539, United States Patent (USP) all are to attempt transverse flow (lateral flow) biochemistry detection test piece is generalized to the example of sxemiquantitative/quantitative analysis.Its principle inhales to have that to draw the test paper of liquid (wicking) effect be base material, judges the amount of determinand by the size that reads conversion zone on the test paper (length of for example variable color length).Error, sample flow velocity inequality, conversion zone in test piece are too short because absorption corpse or other object for laboratory examination and chemical testing volume has, reaction range disperses to cause the not first-class factor of signal power, make that determinand content analysis resultant error is bigger.The determinand content analysis experiment of being done on test paper with Se-Hwan Paek is an example, after Figure 1A shows that a liquid corpse or other object for laboratory examination and chemical testing is sucked into the reaction zone reaction by the below of biochemistry detection test piece, up flows out the test result of reaction zone again.The result who is used for different testing concentrations by left-to-right arrayer for identical test piece.Figure 1B shows conversion zone image enlarged view in the corpse or other object for laboratory examination and chemical testing reaction back test piece.Though this known techniques can be used for the qualitative test of determinand in the corpse or other object for laboratory examination and chemical testing, be unsuitable for directly doing sxemiquantitative/quantitative analysis, the reasons are as follows:
1. because the biochemistry detection test piece of test paper formula has the restriction on material and the processing procedure, make the conversion zone wider width, can't accomplish very elongated.When the amount of determinand is fewer, variable color length is shorter in wide test piece, and when estimating the amount of determinand in a corpse or other object for laboratory examination and chemical testing with visual method according to the length of color change interval, the value of reading error is bigger.
2. because the conversion zone wider width of the biochemistry detection test piece of test paper formula; the uncontrollable unanimity of path when a corpse or other object for laboratory examination and chemical testing up sucks and speed; left side amount is more sometimes for the determinand that feasible quilt intercepts; sometimes partially in or take over; cause the leading edge regular meeting of color change interval have recessed have protruding irregularly shaped, shown in Figure 1B.In addition, when a liquid corpse or other object for laboratory examination and chemical testing is sucked into by the below in the up effusive again process of reaction zone reaction, because without any controlling mechanism, make to run a good foot some determinand some pulls up lame, caused the actor that responds to be dispersed in the reaction zone everywhere phenomenon.This can the leading edge colour developing of reaction range have various levels of GTG to find out from the partial enlarged drawing of Figure 1B.Under this situation, general user is if directly judge the length of color change interval with naked eyes, the recess or the protruding place that should read leading edge on earth, and color is wanted many dark or how shallow scopes that just respond at last, and these all will cause the value of reading to go up great the puzzlement and error.
3. the biochemistry detection test piece of test paper formula must use the material of energy inhalant liquid health check-up body to be made into test piece, and material and framework are limited, therefore are difficult to the directly function of additional on this material ' control flows into corpse or other object for laboratory examination and chemical testing volume '.With the concentration measurement is example, if want to estimate the concentration of determinand in the corpse or other object for laboratory examination and chemical testing according to the length of color change interval, one of prerequisite is to enter the volume that a corpse or other object for laboratory examination and chemical testing that detects in the test piece must be controlled to be prior setting at every turn, otherwise, the corpse or other object for laboratory examination and chemical testing number that enters reaction zone differs, and also can't accurately converse the concentration of determinand even if learn the length of color change interval.The biochemistry detection test piece of test paper formula is difficult on existing material and framework to integrate this function, and the accuracy that is an impediment to when analyzing is promoted.
4. the biochemistry detection test piece of test paper formula is difficult to the directly additional various functions that help the determinand content analysis on this material, for example: the flow through interpolation of speed control, reagent (for example the mark used of antithrombotics, reaction colour generation etc.) of reaction zone and uniform mixing, a single corpse or other object for laboratory examination and chemical testing of the separation of corpse or other object for laboratory examination and chemical testing composition, a corpse or other object for laboratory examination and chemical testing carries out steps such as multinomial test or reacted cleaning, all help to increase the accessibility and the accuracy of analysis, but because material and framework are limited, these functions are difficult to be incorporated on this simple framework.
Therefore, how to develop a kind ofly can effectively handle a corpse or other object for laboratory examination and chemical testing, simplify user's operating process, accurately amount determinand content, and conveniently read the result, even must not add the check and analysis chip of complicated measuring instrument, for this area at present demanding breaking through part urgently.
Summary of the invention
Because the disappearance of known check and analysis technology, the object of the present invention is to provide a micro-fluid chip that can be used for the determinand content analysis, it comprises: a corpse or other object for laboratory examination and chemical testing feeds mouthful, in order to feed a corpse or other object for laboratory examination and chemical testing; One determinand content analysis district, tool one fluid channel, wherein this fluid channel surface lays the plurality of fixed material, and this fluid channel one termination corpse or other object for laboratory examination and chemical testing feeds mouth; And a reaction adjusting portion, in order to regulate the touch opportunity of determinand and plurality of fixed material in the corpse or other object for laboratory examination and chemical testing, make determinand and fixed substance begin to accumulate in regular turn reaction by reacting starting point, reach the concentrated effect of reaction range; Wherein, aforementioned fluid channel has a geometric properties and/or reference mark, in order to read or to converse the determinand content in the corpse or other object for laboratory examination and chemical testing; The previous reaction adjusting portion is aforementioned fluid channel, and this fluid channel comprises upper and lower two substrates, and this substrate material is selected from wetting ability or hydrophobicity material respectively.By producing the range size of concentrating reaction in the aforementioned fluid channel, can learn the determinand content in this corpse or other object for laboratory examination and chemical testing.
In the above-listed narration:
● " fixed substance " refers to and is fixed on fluid channel surface, determinand content analysis district, do not flow away with a corpse or other object for laboratory examination and chemical testing, and can with the material of the intravital determinand of inspection reaction, for example: nucleic acid, part, acceptor, antigen, antibody, ferment, victory peptide, protein or other can with the biological or chemical material of determinand reaction.
● " reaction starting point " is meant that fluid channel connects the starting point that a end that a corpse or other object for laboratory examination and chemical testing feeds mouthful lays fixed substance.
● " accumulation reaction " in regular turn refer to after each determinand particle enters the reaction starting point, time enough and collision opportunity are arranged in the process of advancing and in fluid channel, run at first, and as yet not the fixed substance of effect react.That is to say that test substance is can be because of flow velocity not too fast or do not have collision opportunity and miss as yet the not fixed substance of effect, but advance to next position in the fluid channel with a corpse or other object for laboratory examination and chemical testing.All test substances that enter in the fluid channel are begun to meet with fixed substance in regular turn to produce reaction by the reaction starting point, therefore the scope of reaction will " concentrating " from reacting the determinand content analysis district that starting point begins.Reacted by the fixed substance of leading portion in case examine intravital determinand, though then the fixed substance of back segment run into the residue corpse or other object for laboratory examination and chemical testing flow through, do not had determinand in the corpse or other object for laboratory examination and chemical testing and can react with it.Owing to there is the aitiogenic scope of determinand/fixed substance to concentrate on the fluid channel leading portion, and the fixed substance that determinand does not react after exhausting is positioned at back segment, so the amount of determinand will be proportional to the respond area size of scope of leading portion in the corpse or other object for laboratory examination and chemical testing.If the design of the width of runner has systematicness, then the amount of determinand will be proportional to the length in runner internal reaction zone.
● " reaction adjusting portion " refers to the mechanism that time enough and collision opportunity and fixed substance reaction are arranged in the process that the intravital determinand of inspection is advanced in fluid channel.The method of realization response adjusting portion comprises control corpse or other object for laboratory examination and chemical testing mobile speed and/or set up the various designs that help a disturbance corpse or other object for laboratory examination and chemical testing, increase reaction area and contact probability in runner.
Another object of the present invention is about a kind of determinand content analysis method, comprises: a corpse or other object for laboratory examination and chemical testing is provided; An aforementioned corpse or other object for laboratory examination and chemical testing is fed mouthful fluid channel that imports determinand content analysis district, wherein this fluid channel finishing plurality of fixed material by a corpse or other object for laboratory examination and chemical testing; Regulate the reaction of determinand and this fixed substance in this corpse or other object for laboratory examination and chemical testing, make the autoreaction starting point accumulate reaction in regular turn, reach the effect that reaction range is concentrated; And, can learn the determinand content in this corpse or other object for laboratory examination and chemical testing by aitiogenic range size in the aforementioned fluid channel.
Aforementioned determinand content analysis method can utilize analysis chip of the present invention to reach.
For achieving the above object, the present invention proposes a kind of micro-fluid chip, comprise: a corpse or other object for laboratory examination and chemical testing feeds mouth, in order to feed a corpse or other object for laboratory examination and chemical testing; One determinand content analysis district, tool one fluid channel, wherein this fluid channel surface begins to lay most fixed substances by the reaction starting point, and this fluid channel one termination corpse or other object for laboratory examination and chemical testing feeds mouth; And a reaction adjusting portion, in order to regulate the touch opportunity of determinand and most fixed substances in the corpse or other object for laboratory examination and chemical testing, make determinand and fixed substance begin to accumulate in regular turn reaction by the reaction starting point, reach the concentrated effect of reaction range; Aforementioned fluid channel has a geometric properties and/or reference mark, in order to read or to converse the determinand content in the corpse or other object for laboratory examination and chemical testing.
The invention allows for a kind of determinand content analysis method, comprise: a corpse or other object for laboratory examination and chemical testing is provided; An aforementioned corpse or other object for laboratory examination and chemical testing is imported a fluid channel feed mouth, wherein most fixed substances of this fluid channel finishing; Regulate the touch opportunity of interior determinand of a corpse or other object for laboratory examination and chemical testing and most fixed substances, make determinand and fixed substance begin to accumulate in regular turn reaction, reach the concentrated effect of reaction range by the reaction starting point; And, can learn the content of determinand in this corpse or other object for laboratory examination and chemical testing by aitiogenic range size in the aforementioned fluid channel.
The invention allows for a kind of determinand content analysis method, comprise: a corpse or other object for laboratory examination and chemical testing is provided; An aforementioned corpse or other object for laboratory examination and chemical testing is imported a fluid channel feed mouth, wherein most fixed substances of this fluid channel finishing; Regulate in the corpse or other object for laboratory examination and chemical testing and treat
The present invention has further proposed a kind of determinand content analysis method, comprising: a corpse or other object for laboratory examination and chemical testing is provided; The fluid channel that an aforementioned corpse or other object for laboratory examination and chemical testing is imported the described micro-fluid chip of claim 1 feeds mouth, wherein most fixed substances of this fluid channel finishing; Regulate the touch opportunity of interior determinand of a corpse or other object for laboratory examination and chemical testing and most fixed substances, make determinand and fixed substance begin to accumulate in regular turn reaction, reach the concentrated effect of reaction range by the reaction starting point; And, can learn the determinand content in this corpse or other object for laboratory examination and chemical testing by aitiogenic range size in the aforementioned fluid channel.
Wherein, the reaction of determinand and this fixed substance in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting, be that the upper and lower two substrates material characteristic that comprises by aforementioned fluid channel is controlled corpse or other object for laboratory examination and chemical testing progressive speed, reach the requirement that accumulation is reacted in regular turn, wherein this substrate material is selected from wetting ability or hydrophobicity material respectively.
Description of drawings
Figure 1A, 1B show known techniques test paper chromatography biochemistry detection test piece synoptic diagram and part signal image enlarged view thereof.
Fig. 2 is the enforcement aspect of a current velocity controller for its reaction adjusting portion of micro-fluid chip of determinand content analysis of the present invention.
Fig. 3 is the enforcement aspect of fluid channel finishing for its reaction adjusting portion of micro-fluid chip of determinand content analysis of the present invention.
The enforcement aspect of the internal diameter that Fig. 4 A differs for fluid channel width for its reaction adjusting portion of the micro-fluid chip of determinand content analysis of the present invention.
Fig. 4 B is the local amplification of the fluid channel of Fig. 4 A.
Fig. 5 A for the micro-fluid chip of determinand content analysis of the present invention with the geometric properties of fluid channel a embodiment as the value of reading identification reference.
Fig. 5 B for the micro-fluid chip of determinand content analysis of the present invention with the geometric properties of fluid channel another embodiment as the value of reading identification reference.
Fig. 6 A is an embodiment of the reference mark of the micro-fluid chip fluid channel of determinand content analysis of the present invention.
Fig. 6 B is another embodiment of the reference mark of the micro-fluid chip fluid channel of determinand content analysis of the present invention.
Fig. 7 A shows that the micro-fluid chip series connection plural groups corpse or other object for laboratory examination and chemical testing of determinand content analysis of the present invention feeds mouth, determinand content analysis district and reaction adjusting portion.
Fig. 7 B shows that the micro-fluid chip of a determinand content analysis of the present invention plural groups corpse or other object for laboratory examination and chemical testing in parallel feeds mouth, determinand content analysis district and reaction adjusting portion.
Fig. 8 illustrates that the more known biochemistry detection test piece of determinand content analysis chip of the present invention has the high-resolution principle.
The drawing reference numeral explanation:
1---determinand content analysis micro-fluid chip
A 2---corpse or other object for laboratory examination and chemical testing feeds mouth
3---determinand content analysis district
The 4---fluid channel
The 6---reference mark
41---reacts starting point
The 51---current velocity controller
The material of 52---fluid channel finishing
The internal diameter that 53---fluid channel width differs
Bibliography:
[1]Se-Hwan?Paek，et.al.，Development?of?Rapid?One-StepImmunochromatographic?Assay，Methods?22，p.53-p.60，2000
Embodiment
One of determinand content analysis micro-fluid chip of the present invention is implemented aspect as shown in Figure 2, and this determinand content analysis micro-fluid chip 1 mainly comprises: a corpse or other object for laboratory examination and chemical testing feeds mouth 2, in order to feed a corpse or other object for laboratory examination and chemical testing; One determinand content analysis district 3, tool one fluid channel 4, wherein these fluid channel 4 surfaces lay plurality of fixed material (representing with the netted decorative pattern on the fluid channel), and these fluid channel 4 one termination corpse or other object for laboratory examination and chemical testing feed mouth; And a reaction adjusting portion, in order to regulate in the corpse or other object for laboratory examination and chemical testing touch opportunity of plurality of fixed materials in the determinand and fluid channel 4, determinand and fixed substance are reacted by reaction starting point 41 beginnings accumulation in regular turn, reach the concentrated effect of reaction range.Accumulate on the determinand/fixed substance reaction range (the solid black lines zone of fluid channel 4) of leading portion by aforementioned fluid channel 4, and, can learn the determinand content in this corpse or other object for laboratory examination and chemical testing with reference to the geometric characteristic or the external marking scale 6 of fluid channel 4.In this enforcement aspect, the previous reaction adjusting portion is a current velocity controller 51, and for example: the pump of may command flow velocity links fluid channel 4 and feeds a mouthful opposite the other end with a corpse or other object for laboratory examination and chemical testing.
In another aspect of the present invention, the previous reaction adjusting portion also can be the fluid channel material in determinand content analysis district, controls corpse or other object for laboratory examination and chemical testing progressive speed by the parent/hydrophobicity of fluid channel material, reaches the demand that accumulation is reacted in regular turn.Make the groove of various section shapes on a substrate, engages with another plane or substrate with groove, the groove between the substrate of two sides promptly forms fluid channel, can supply micro fluid carry out each task in runner.Microfluid mobile mode in runner is influenced by groove surfaces situation (i.e. the material of two plate bases).Substrate material then can be selected from wetting ability or hydrophobicity material, on/combination of the material of hypocoxa can be: wetting ability/wetting ability, hydrophilic/hydrophobic, hydrophobicity/wetting ability or hydrophobicity/hydrophobicity.The aforesaid base plate material is preferable to be comprised: poly-dimethoxy siloxanes (polydimethylsiloxane, PDMS), polycarbonate (polycarbonate, PC), the rare cigarette polymkeric substance of ring (cyclic olefin copolymers, COC), polystyrene (polystyrene, PS), glass or polymethylmethacrylate (polymethylmethacrylate, PMMA).
Fig. 3 shows another enforcement aspect of the present invention, the reaction adjusting portion of wherein aforementioned determinand content analysis micro-fluid chip 1 of the present invention also can be at aforementioned fluid channel 4 surface locals or comprehensive material of modifying 52 (oblique line part), for example, but be not limited to: particular functional base, hydroaropic substance and/or lyophobic dust, with the further local rate of advance of adjusting a corpse or other object for laboratory examination and chemical testing different sections in runner, reach the demand that accumulation is reacted in regular turn.
Fig. 4 A shows an enforcement aspect more of the present invention, the reaction adjusting portion of aforementioned determinand content analysis micro-fluid chip 1 of the present invention also can be the internal diameter 53 that fluid channel 4 cross-sectional shapes change and width differs in determinand content analysis district, with the rate of advance or the flow pattern of a control corpse or other object for laboratory examination and chemical testing.Fig. 4 B shows the profile of fluid channel 4 crevices of Fig. 4 A.
In another aspect of the present invention, the internal surface that the reaction adjusting portion of wherein aforementioned determinand content analysis micro-fluid chip is included in fluid channel is provided with ridge, to increase the area that lays of fixed substance, and help microfluid to advance in the flow-disturbing mode, effectively impel determinand and fixed substance contact probability to improve.
Fig. 5 A is shown in of the present invention one and implements in the aspect, the reaction range of the fluid channel 4 of aforementioned determinand content analysis micro-fluid chip 1 can be with reference to the geometric properties of fluid channel 4 and is learnt determinand content in the corpse or other object for laboratory examination and chemical testing, the geometric properties of aforementioned fluid channel 4 is several successive bend structures, arrive which bend by the observing response scope and construct the determinand content that corresponding to learn in this corpse or other object for laboratory examination and chemical testing, for example: low amount, middle amount or a large amount etc.The geometric properties that Fig. 5 B is shown in aforementioned determinand content analysis micro-fluid chip 1 fluid channel 4 is a plurality of more intensive continuous bend structures, can be quantitative more accurately.The geometric properties of fluid channel 4 only of the present invention is not limited to the bend shape structure of this enforcement aspect, the visual actual detected of its shape and length needs and adjusts, for example: rectangle bend, volution bend etc. and unrestricted, also can utilize other kind geometric properties to reach conveniently recognized and learn the effect of determinand content.
Fig. 6 A and Fig. 6 B show determinand content analysis micro-fluid chip 1 of the present invention, the pipeline of its fluid channel 4 can correspondence be provided with reference mark 6, this reference mark 6 can be arranged at by the fluid channel, also can be arranged at (figure does not show) on the fluid channel 4, learn the determinand content in the corpse or other object for laboratory examination and chemical testing by the pairing scale of observing response scope.
The geometric properties of aforementioned fluid channel 4 and reference mark 6 are can be provided with in the lump or be provided with separately to help to learn the determinand content in the corpse or other object for laboratory examination and chemical testing.Another aspect of the present invention is, the numerical value that reads via the geometric properties and the reference mark 6 of aforementioned fluid channel 4 can be further converses the content of determinand in the actual corpse or other object for laboratory examination and chemical testing by a calibration curve or experiment contrast table.
In another enforcement aspect of the present invention, determinand content analysis micro-fluid chip can link many group corpse or other object for laboratory examination and chemical testing by the mode of serial or parallel connection and feed mouth, organizes determinand content analysis district or many group reactions adjusting portion more, it is unrestricted that but its banded corpse or other object for laboratory examination and chemical testing feeds the number of mouth, determinand content analysis district or reaction adjusting portion, each group determinand content analysis district can lay identical or different fixed substance, can as comparison with or measure different determinands.Fig. 7 A shows that determinand content analysis micro-fluid chip 1 a tandem junction unification corpse or other object for laboratory examination and chemical testing of the present invention feeds mouth 2, a plurality of determinand content analysis district 3 and a reaction adjusting portion, wherein this reaction adjusting portion is to be example with current velocity controller 51, and this reaction adjusting portion can also be fluid channel material, fluid channel surface local or the internal diameter or the change of fluid channel cross-sectional shape that differ of the set ridge of material, the fluid channel internal surface of modification and/or fluid channel width comprehensively certainly.Fig. 7 B shows that determinand content analysis micro-fluid chip of the present invention 1 parallel connection feeds mouth 2, a plurality of determinand content analysis district 3 and a reaction adjusting portion in conjunction with a corpse or other object for laboratory examination and chemical testing in addition, wherein this reaction adjusting portion is an example with current velocity controller 51, and this reaction adjusting portion can also be that internal diameter or the fluid channel cross-sectional shape that set ridge of fluid channel material, fluid channel surface local or comprehensive material, fluid channel internal surface of modifying and/or fluid channel width differ changes certainly.
The fixed substance that is laid on the fluid channel of determinand content analysis micro-fluid chip of the present invention comprises: nucleic acid, part, acceptor, antigen, antibody, ferment, victory peptide, protein or other can with the biological or chemical material of determinand reaction.
Determinand content analysis micro-fluid chip of the present invention can further comprise a volume regulatory region, and this volume-adjustment district can be the liquid element that dams, and sends into reaction zone in order to the corpse or other object for laboratory examination and chemical testing volume that intercepts prior setting, for example, but is not limited to: the thumb pump.
Determinand content analysis micro-fluid chip of the present invention can further comprise an expulsion element, in order to contained gas in the discharging corpse or other object for laboratory examination and chemical testing, avoids causing the error of measuring corpse or other object for laboratory examination and chemical testing volume because bubble exists.
Determinand content analysis micro-fluid chip of the present invention, can further comprise a pre-treatment district, be used to carry out that the separation of corpse or other object for laboratory examination and chemical testing composition, decomposition, catalysis, change state, modification, mark, reagent mix, anti-freezing are solid, anticoagulation, anti-degraded, degeneration, dilution, drying, concentrate, steps such as heating and cooling, adjustment pH value or cleaning.Aforesaid pre-treatment district can comprise, for example, but is not limited to: a determinand labeled reactant district, will examine intravital determinand mark in addition.Wherein aforementioned determinand mark is can utilize to comprise: ferment, fluorescent, cold light, nanoparticle or other have the material that is chromatic effect, as: be antibody that coloured particles joins or other has the reagent that is chromatic effect.
Determinand content analysis micro-fluid chip of the present invention can further comprise a post processing zone, is used to carry out mark, adds steps such as reagent, cleaning, drying or heating and cooling.Wherein mark is meant and utilizes ferment, fluorescent, cold light, nanoparticle or other to have the material that is chromatic effect, as: be antibody that coloured particles joins or other has the reagent that is chromatic effect.
Another object of the present invention also provides a kind of determinand content analysis method, comprises: a corpse or other object for laboratory examination and chemical testing is provided; An aforementioned corpse or other object for laboratory examination and chemical testing is fed mouthful fluid channel that imports determinand content analysis district, wherein this fluid channel finishing plurality of fixed material by a corpse or other object for laboratory examination and chemical testing; Regulate in this corpse or other object for laboratory examination and chemical testing determinand and this fixed substance and accumulate reaction in regular turn, reach the effect that reaction range is concentrated by the reaction starting point; And, can learn the content of determinand in this corpse or other object for laboratory examination and chemical testing by aitiogenic range size in the aforementioned fluid channel.So method of the present invention can not need to use CCD or other image analysing computer software with the identification color change interval.
Aforesaid determinand content analysis method, in wherein aforementioned this corpse or other object for laboratory examination and chemical testing of adjusting the reaction of determinand and this fixed substance be by a current velocity controller with control corpse or other object for laboratory examination and chemical testing progressive speed, reach the requirement that accumulation is reacted in regular turn; Also can control corpse or other object for laboratory examination and chemical testing progressive speed by the upper and lower two substrates material characteristic that aforementioned fluid channel comprised, reach the requirement that accumulation is reacted in regular turn, wherein this substrate material is to be selected from wetting ability or hydrophobicity material respectively.
The reaction of determinand and this fixed substance also can utilize the internal diameter of fluid channel to have the design that width differs or cross-sectional shape changes in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting, to adjust corpse or other object for laboratory examination and chemical testing progressive speed and mobile pattern.
The reaction of determinand and this fixed substance is by the internal surface in fluid channel ridge to be set in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting, to increase the area that lays of fixed substance, and help microfluid to advance in the flow-disturbing mode, effectively impel determinand and fixed substance contact probability to improve.
In addition, the reaction of determinand and this fixed substance is by at the local of fluid channel surface or modify particular functional base, hydroaropic substance and/or lyophobic dust and control corpse or other object for laboratory examination and chemical testing progressive speed comprehensively in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting, reaches the demand that accumulation is reacted in regular turn.Aforesaid determinand content analysis method of the present invention can further comprise a volume regulating step, a steps of exhausting, a pre-treatment step and/or a post-processing step.
Wherein aforementioned pre-treatment step comprises that the separation of corpse or other object for laboratory examination and chemical testing composition, decomposition, catalysis, change state, modification, mark, reagent mix, anti-freezing are solid, anticoagulation, anti-degraded, degeneration, dilution, drying, concentrate, steps such as heating and cooling, adjustment pH value or cleaning.Wherein aforesaid post-processing step comprises: steps such as mark, interpolation reagent, cleaning, drying or heating and cooling.
Aforesaid markers step can comprise by adding: ferment, fluorescent, cold light, nanoparticle, be antibody that coloured particles joins or other and have the material that is chromatic effect or reagent to reach the purpose of mark.
Determinand content analysis method provided by the present invention can utilize determinand content analysis chip of the present invention to reach.
Fig. 8 is compared to the test paper chromatography biochemistry detection test piece that shows known techniques; the determinand content analysis chip the principle why value of reading resolving power can improve of the present invention; general biochemistry detection test piece wider width; so color change interval leading edge regular meeting presents the GTG of irregularly shaped and different levels; the accuracy of the influence value of reading; determinand content analysis district on the micro-fluid chip of the present invention is elongated fluid channel; just the irregularly shaped area of variable color (shown in the square-shaped frame line) in the signal zone of biochemistry detection test piece is launched into the microfluid pipeline; so, erose color change interval area stool and urine can be exchanged into aitiogenic range size in the fluid channel.For example, suppose the variable color area of known techniques is decided to be length 10 unit widths 10 units, the present invention is if be reduced to 1/10th (i.e. 1 units) with width, it is that ten times (i.e. 100 units) then can be according to the length that the determinand reaction is arranged in the determinand content analysis district microchannel that length is increased, 87 units for example, just can more accurately make the amount of testing sample, increase resolving power, this is that known detection test piece is beyond one's reach.
Another advantage of the present invention for the function that can integrate ' control flow into a corpse or other object for laboratory examination and chemical testing volume ' on same chip.With the concentration measurement is example, if want to estimate according to the length of color change interval the concentration of determinand in the corpse or other object for laboratory examination and chemical testing, one of prerequisite is to enter the volume that a corpse or other object for laboratory examination and chemical testing that detects in the test piece must be controlled to be prior setting at every turn, could accurately converse the concentration of determinand.The present invention can make chip with various polymers, silicon, glass or other material, and integrates the function that control flows into corpse or other object for laboratory examination and chemical testing volume on chip, and the accuracy when therefore helping the determinand content analysis promotes.In addition, other function for example interpolation of reagent and uniform mixing, a single corpse or other object for laboratory examination and chemical testing is carried out steps such as multinomial test or reacted cleaning, can be incorporated on the same chip, helps to increase the accessibility and the accuracy of determinand content analysis.Be difficult to integrate the situation of various complicated additional function compared to the test piece of aforementioned test paper chromatography biochemistry detection, the present invention has progressive.
The present invention is by the particular design of corpse or other object for laboratory examination and chemical testing flow pattern, and the feasible color change interval that responds begins accumulation by the starting point of conversion zone, reaches the effect that reaction range is concentrated.As previously mentioned, this kind technology can be used for need not adding instrument and the application of directly reading the content of determinand.Yet for adding instrument carrying out for the quantitative mode of determinand, this kind technology also of great use.For example, want to measure the fluorescent brightness of being demarcated on the determinand foundation as determinand content with instrument, determinand is dispersed in reacting arbitrarily in the reaction zone everywhere if leave, determinand content in the unit surface is low, and then employed instrumental sensitivity must enough high markd determinands that just is enough to detect.Because the present invention can impel reaction range to concentrate, therefore the reaction range of required observation and measurement is dwindled, and the signal strength in the unit surface improves, and makes instrumental sensitivity too highly still can be measured effect accurately.Therefore also the amount applicable to determinand is few in the present invention, or accuracy of measurement has relatively high expectations etc., needs the situation with the auxiliary determinand content analysis of instrument.
Except sxemiquantitative/quantitative analysis, the present invention also is applicable to qualitative analysis.By the control of corpse or other object for laboratory examination and chemical testing flow pattern, make reaction range concentrate, help the qualitative analysis when determinand content is low in the corpse or other object for laboratory examination and chemical testing to judge whether to surpass threshold value.
Generally speaking, chip of the present invention and the test piece of test paper chromatography biochemistry detection are compared, and that the present invention can be used for is qualitative, sxemiquantitative and detection by quantitative, and its colour developing and the value of reading resolving power height, and it is more accurate to measure, and can add corpse or other object for laboratory examination and chemical testing pre-treatment/advantages such as post-reaction treatment function.Compare with other analysis chip, the advantage that needn't use complex instrument can detect determinand content is then arranged.
About aforementioned and other technology contents, characteristics and effect of the present invention, in the following detailed description that cooperates with reference to graphic preferred embodiment, can clearly understand.Following examples are used for further setting forth advantage of the present invention, are not to be used to limit claim of the present invention.
Embodiment
The invention relates to a kind of devices and methods therefor that on micro-fluid chip, carries out determinand content analysis in the corpse or other object for laboratory examination and chemical testing, it is characterized in that for making determinand and the fixed substance reaction of modifying microchannel surface on chip, concentrate reaction by producing in the microchannel, again according to the content of the range size of reacting with determinand in the judgement corpse or other object for laboratory examination and chemical testing.
Present embodiment utilizes micro electronmechanical processing procedure (MEMS process) to make micro-fluid chip of the present invention with thick photoresistance processing procedure and flexible high polymer material, and tests different determinand content in the corpse or other object for laboratory examination and chemical testing respectively.
Substrate on this chip has the groove that forms fluid channel, and material is the flexible high polymer material of bio-compatibility, in order to the standard corpse or other object for laboratory examination and chemical testing path of passing through; Following plate substrate material is a glass, and upper and lower base plate is combined to form the chip with fluid channel.Corpse or other object for laboratory examination and chemical testing on chip feeds and adds the whole blood that is mixed with anti-coagulant EDTA in the mouth, utilization adds pump as current velocity controller, whole blood is flowed with being all deeply in 100 microns the elongated fluid channel wide, and its velocity of flow can be controlled according to the pressure size that puts on pump.
Utilize determinand content analysis micro-fluid chip 1 as shown in Figure 2 to experimentize, the wide 100 μ m of the runner of the microchannel 4 in the determinand content analysis district 3 on the chip, dark 100 μ m, and U type fluid channel 4 every section straight length L are 8mm, be furnished with the anti-ageing rat immune globulin G of fixed substance goat (Goat-anti-mouse-IgG, concentration 5.6mg/ml) on it.A corpse or other object for laboratory examination and chemical testing (containing the determinand Mouse-IgG C that indicates through nano Au particle) is fed mouthful 2 importing determinand content analysis districts 3 by a corpse or other object for laboratory examination and chemical testing.Advance in fluid channel 4 by current velocity controller 51 control samples in addition, speed is 0.8mm/min, fully reacts so that examine the fixed substance that intravital determinand and cloth is put in microchannel 4 surfaces.
The application of general determinand content analysis all is that the determinand that the corpse or other object for laboratory examination and chemical testing with equal volume contains different concns is done test.In the present embodiment,, use identical testing concentration instead, but the corpse or other object for laboratory examination and chemical testing of different volumes is tested also in direct ratio the increasing of amount of the contained determinand of the adding many persons of corpse or other object for laboratory examination and chemical testing volume in order to be easy to the confirmatory experiment result.Present embodiment is done experiment with two identical chips.Chip one and chip two are that a corpse or other object for laboratory examination and chemical testing that captures 1.5 μ l and 3 μ l respectively (includes the determinand Mouse-IgG CGC of same concentrations, OD540=50), imports determinand content analysis district 3.A corpse or other object for laboratory examination and chemical testing is flowed through after the fluid channel 4, and the fixed substance on the tube wall (Goat-anti-mouse-IgG) will carry out antigen antibody reaction with determinand, catch determinand.Since determinand in conjunction with purpuric nano Au particle as sign, therefore still be purple stay in the tube wall of runner with the fixed substance reaction bonded after.From the reaction starting point, have the zone of this kind reaction can present purple, along with determinand is exhausted by reaction, though unreacted zone has a corpse or other object for laboratory examination and chemical testing to flow through still keep transparent.By the fluid channel 4 aitiogenic purple scopes of observing determinand content analysis district, see through the content that the experiment contrast table can be estimated determinand in the corpse or other object for laboratory examination and chemical testing.
Experimental result shows: fluid channel 4 length that respond in the chip one be about 88mm+/-4mm, the fluid channel that responds 4 length of chip two be about 160mm+/-8mm.The determinand content of chip two is the twice of chip one, the also about twice of the range size of its microchannel reaction of test result, and this shows that promptly the length of fluid channel conversion zone can directly reflect the content number of determinand.Prove thus by micron-sized fluid channel and cooperate the reaction regulation mechanism of corpse or other object for laboratory examination and chemical testing flow rate control can reach reaction in regular turn that the effect in the range set is used for sxemiquantitative/quantitative analysis.
The present embodiment purpose is the asynchronous measurement of determinand content in a test corpse or other object for laboratory examination and chemical testing.The material of micro-fluid chip, processing procedure are identical with embodiment one, and U type fluid channel 4 every section straight length L are 8mm, but the geometrical shape of runner changes and adopt the variation that width differs, the fluid channel of width 300um every the 2mm distance be the one-sided asymmetric 150um of being narrowed once.Cloth is placed with the anti-ageing rat immune globulin G of fixed substance goat (Goat-anti-mouse-IgG, concentration 5.6mg/ml) on the fluid channel.For shortening detection time, this routine flow velocity is controlled to be 12mm/min by adding pump, and is fast than embodiment one.
Present embodiment is done experiment with two identical chips.The corpse or other object for laboratory examination and chemical testing that chip one is tested indicates determinand (Mouse-IgG CGC for containing through nano Au particle, OD540=50) corpse or other object for laboratory examination and chemical testing of 4ul, and chip two employed corpse or other object for laboratory examination and chemical testing are determinand (Mouse-IgG CGC, OD540=50) 2ul adds the water of 2ul, so concentration is chip one interior corpse or other object for laboratory examination and chemical testing concentration half.
Testing method is identical with embodiment one, and a corpse or other object for laboratory examination and chemical testing is flowed through after the fluid channel 4, the fixed substance reaction bonded of arranging in determinand and the fluid channel and the tube wall that stays in runner is purple.Observe the fluid channel 4 aitiogenic purple scopes in determinand content analysis district, cooperate the experiment contrast table can estimate the content of determinand in the corpse or other object for laboratory examination and chemical testing.The violet region length of chip one be 136mm+/-20mm, the violet region length of chip two be 72mm+/-16mm, approaching with expected results, concentration and length is near proportionlity, but because velocity ratio embodiment one is fast, and is big slightly in the limit of error.
The present embodiment purpose is the asynchronous measurement of determinand content in a test corpse or other object for laboratory examination and chemical testing.The material of micro-fluid chip, processing procedure are identical with embodiment two, U type fluid channel 4 every section straight length L are 8mm, runner is also adopted variation (one-sided asymmetric the narrowing down that width differs, systematicness alternately changes between width 150um-300um), but set up ridge in the runner, the liquid in the runner is advanced in the mode of flow-disturbing.Cloth is placed with the anti-ageing rat immune globulin G of fixed substance goat (Goat-anti-mouse-IgG, concentration 5.6mg/ml) on the fluid channel.This routine flow velocity is controlled to be 12mm/min by adding pump, and is identical with embodiment two.
Present embodiment is done experiment with two identical chips.The corpse or other object for laboratory examination and chemical testing that chip one is tested indicates determinand (Mouse-IgG CGC for containing through nano Au particle, OD540=50) corpse or other object for laboratory examination and chemical testing of 6ul, and chip two employed corpse or other object for laboratory examination and chemical testing are determinand (Mouse-IgG CGC, OD540=50) 3ul adds the water of 3ul, so concentration is chip one testing concentration half.
Testing method is identical with embodiment two, and a corpse or other object for laboratory examination and chemical testing is flowed through after the fluid channel 4, the fixed substance reaction bonded of arranging in determinand and the fluid channel and the tube wall that stays in runner is purple.The fluid channel 4 of observing determinand content analysis district has aitiogenic purple scope can learn the content of determinand in the corpse or other object for laboratory examination and chemical testing.The violet region length of chip one be 112mm+/-8mm, the violet region length of chip two be 64mm+/-8mm, approaching with expected results, concentration and length are near proportionlity, and owing to effectively change flow pattern, though flow velocity is identical with embodiment two, limit of error is less.
Can learn that by previous embodiment micro-fluid chip of the present invention can be used as the instrument of determinand content analysis, and geometric properties and/or reference mark by the microchannel in the determinand content analysis district, can directly learn the amount of determinand in the corpse or other object for laboratory examination and chemical testing, immediately obtain detected result, do not need by other image analysing computer software or instrument.
Though the present invention discloses as above with preferred embodiment, so it is not in order to limiting the present invention, anyly is familiar with this skill person; without departing from the spirit and scope of the present invention, when being used for a variety of modifications and variations, therefore; protection scope of the present invention is as the criterion when looking the claim person of defining.
Claims (33)
1. micro-fluid chip comprises:
One corpse or other object for laboratory examination and chemical testing feeds mouth, in order to feed a corpse or other object for laboratory examination and chemical testing;
One determinand content analysis district, tool one fluid channel, wherein this fluid channel surface begins to lay most fixed substances by the reaction starting point, and this fluid channel one termination corpse or other object for laboratory examination and chemical testing feeds mouth; And
One reaction adjusting portion in order to the touch opportunity of determinand in the adjusting corpse or other object for laboratory examination and chemical testing with most fixed substances, makes determinand and fixed substance begin to accumulate in regular turn reaction by the reaction starting point, reaches the concentrated effect of reaction range;
Wherein, aforementioned fluid channel has a geometric properties and/or reference mark, in order to read or to converse the determinand content in the corpse or other object for laboratory examination and chemical testing; The previous reaction adjusting portion is aforementioned fluid channel, and this fluid channel comprises upper and lower two substrates, and this substrate material is selected from wetting ability or hydrophobicity material respectively.
2. micro-fluid chip as claimed in claim 1 is characterized in that, the previous reaction adjusting portion is a current velocity controller.
3. micro-fluid chip as claimed in claim 2 is characterized in that, aforesaid current velocity controller is linked to the other end that relative determinand content analysis district feeds the fluid channel of mouth.
4. micro-fluid chip as claimed in claim 2 is characterized in that, aforesaid current velocity controller is a pump.
5. micro-fluid chip as claimed in claim 1 is characterized in that, the aforesaid base plate material comprises: poly-dimethoxy siloxanes, polycarbonate, the rare cigarette polymkeric substance of ring, polystyrene, glass or polymethylmethacrylate.
6. micro-fluid chip as claimed in claim 1 is characterized in that, the previous reaction adjusting portion comprises the design that fluid channel internal diameter width differs or cross-sectional shape changes.
7. micro-fluid chip as claimed in claim 1 is characterized in that the internal surface that the previous reaction adjusting portion comprises fluid channel is provided with ridge.
8. micro-fluid chip as claimed in claim 1 is characterized in that, the previous reaction adjusting portion is contained in the surface local of this fluid channel or modifies particular functional base, hydroaropic substance and/or lyophobic dust comprehensively.
9. micro-fluid chip as claimed in claim 1 is characterized in that, comprises a volume regulatory region, enters the corpse or other object for laboratory examination and chemical testing volume in determinand content analysis district with control.
10. micro-fluid chip as claimed in claim 9 is characterized in that, aforementioned volume-adjustment district comprises the liquid element that dams.
11. micro-fluid chip as claimed in claim 10 is characterized in that, the aforementioned liquids element that dams is the thumb pump.
12. micro-fluid chip as claimed in claim 1 is characterized in that, comprises an expulsion element.
13. micro-fluid chip as claimed in claim 1 is characterized in that, comprises a pre-treatment district.
14. micro-fluid chip as claimed in claim 13 is characterized in that, aforesaid pre-treatment district comprises a corpse or other object for laboratory examination and chemical testing determinand labeled reactant district.
15. micro-fluid chip as claimed in claim 14 is characterized in that, the utilization of aforesaid corpse or other object for laboratory examination and chemical testing determinand mark comprises: ferment, fluorescent, cold light, nanoparticle or be antibody that coloured particles joins to reach the purpose of mark.
16. micro-fluid chip as claimed in claim 1 is characterized in that, comprises a post processing zone.
17. micro-fluid chip as claimed in claim 1 is characterized in that, the most group of a series connection corpse or other object for laboratory examination and chemical testing feeds mouth, most group determinand content analysis districts or most group reaction adjusting portion.
18. micro-fluid chip as claimed in claim 1 is characterized in that, most group corpse or other object for laboratory examination and chemical testing in parallel feed mouth, most group determinand content analysis districts or most group reaction adjusting portion.
19. micro-fluid chip as claimed in claim 1 is characterized in that, the aforementioned fixation material comprises: nucleic acid, part, acceptor, antigen, antibody, ferment, victory peptide or protein.
20. a determinand content analysis method comprises:
A corpse or other object for laboratory examination and chemical testing is provided;
An aforementioned corpse or other object for laboratory examination and chemical testing is imported a fluid channel feed mouth, wherein most fixed substances of this fluid channel finishing;
Regulate the touch opportunity of interior determinand of a corpse or other object for laboratory examination and chemical testing and most fixed substances, make determinand and fixed substance begin to accumulate in regular turn reaction, reach the concentrated effect of reaction range by the reaction starting point; And
By aitiogenic range size in the aforementioned fluid channel, learn the content of determinand in this corpse or other object for laboratory examination and chemical testing;
Wherein, the reaction of determinand and this fixed substance in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting, be that the upper and lower two substrates material characteristic that comprises by aforementioned fluid channel is controlled corpse or other object for laboratory examination and chemical testing progressive speed, reach the requirement that accumulation is reacted in regular turn, wherein this substrate material is selected from wetting ability or hydrophobicity material respectively.
21. determinand content analysis method as claimed in claim 20 is characterized in that, the reaction of determinand and this fixed substance in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting, be by a current velocity controller with control corpse or other object for laboratory examination and chemical testing progressive speed, reach the requirement that accumulation is reacted in regular turn.
22. determinand content analysis method as claimed in claim 20, it is characterized in that, the reaction of determinand and this fixed substance in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting is to utilize the internal diameter of fluid channel to have the design that width differs or cross-sectional shape changes, to adjust corpse or other object for laboratory examination and chemical testing progressive speed.
23. determinand content analysis method as claimed in claim 20, it is characterized in that the reaction of determinand and this fixed substance is by at the local of fluid channel surface or modify particular functional base, hydroaropic substance and/or lyophobic dust and control comprehensively in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting.
24. determinand content analysis method as claimed in claim 20, it is characterized in that, the reaction of determinand and this fixed substance in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting, be ridge to be set by internal surface in fluid channel, to increase the area that lays of fixed substance, and help microfluid to advance in the flow-disturbing mode, effectively impel determinand and fixed substance contact probability to improve.
25. determinand content analysis method as claimed in claim 20 is characterized in that, comprises a volume regulating step, enters the corpse or other object for laboratory examination and chemical testing volume in determinand content analysis district with control.
26. determinand content analysis method as claimed in claim 20 is characterized in that, comprises a steps of exhausting.
27. determinand content analysis method as claimed in claim 20 is characterized in that, comprises a pre-treatment step.
28. determinand content analysis method as claimed in claim 27, it is characterized in that, aforesaid pre-treatment step comprises that the separation of corpse or other object for laboratory examination and chemical testing composition, decomposition, catalysis, change state, modification, mark, reagent mix, anti-freezing are solid, anticoagulation, anti-degraded, degeneration, dilution, drying, concentrate, heating and cooling, adjustment pH value or cleaning step.
29. determinand content analysis method as claimed in claim 20 is characterized in that, comprises a post-processing step.
30. determinand content analysis method as claimed in claim 29 is characterized in that, aforesaid post-processing step comprises: mark, interpolation reagent, cleaning, drying or heating and cooling step.
31., it is characterized in that aforesaid markers step is comprised by adding as claim 28 or 30 described determinand content analysis methods: ferment, fluorescent, cold light, nanoparticle or be antibody that coloured particles joins to reach the purpose of mark.
32. determinand content analysis method as claimed in claim 20 is characterized in that, according to aitiogenic range size in the fluid channel, with reference to the geometric properties of fluid channel and/or reference mark and read determinand content in the corpse or other object for laboratory examination and chemical testing.
33. a determinand content analysis method comprises:
A corpse or other object for laboratory examination and chemical testing is provided;
The fluid channel that an aforementioned corpse or other object for laboratory examination and chemical testing is imported the described micro-fluid chip of claim 1 feeds mouth, wherein most fixed substances of this fluid channel finishing;
Regulate the touch opportunity of interior determinand of a corpse or other object for laboratory examination and chemical testing and most fixed substances, make determinand and fixed substance begin to accumulate in regular turn reaction, reach the concentrated effect of reaction range by the reaction starting point; And
By aitiogenic range size in the aforementioned fluid channel, learn the determinand content in this corpse or other object for laboratory examination and chemical testing;
Wherein, the reaction of determinand and this fixed substance in this corpse or other object for laboratory examination and chemical testing of aforementioned adjusting, be that the upper and lower two substrates material characteristic that comprises by aforementioned fluid channel is controlled corpse or other object for laboratory examination and chemical testing progressive speed, reach the requirement that accumulation is reacted in regular turn, wherein this substrate material is selected from wetting ability or hydrophobicity material respectively.
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| CN101452003B (en) * | 2007-11-28 | 2012-08-22 | 中国科学院大连化学物理研究所 | Liquid storage pool micropump completely-integrated in micro-fluidic chip |
| TWI476406B (en) * | 2011-11-10 | 2015-03-11 | Apex Biotechnology Corp | Reaction cassette and assay device |
| JP6120518B2 (en) * | 2012-10-10 | 2017-04-26 | 公益財団法人かずさＤｎａ研究所 | Simple measuring instrument |
| CN103323605B (en) * | 2013-06-18 | 2017-06-30 | 杭州普施康生物科技有限公司 | A kind of micro-fluidic chip of saccharification hemoglobin immune detection |
| CN103558394B (en) * | 2013-10-24 | 2015-06-10 | 山东大学 | Sample feeding device for measuring trace target substance |
| CN103934049B (en) * | 2014-04-14 | 2016-06-08 | 西安交通大学 | A kind of quantitative care diagnostic micro-fluidic chip of scale-type and preparation method thereof |
| CN107148468B (en) * | 2014-07-30 | 2021-04-27 | 北京中科纳泰生物科技有限公司 | Microfluidic device with smooth surface for enrichment of rare cells and biomarkers from biological fluids |
| TWI530683B (en) * | 2014-10-16 | 2016-04-21 | 國立清華大學 | A fabric-base biochemical detecting device and the fabricating method thereof |
| TWI635907B (en) | 2015-04-30 | 2018-09-21 | 伊勒伯科技股份有限公司 | System and method for detecting biomarker |
| CN106918578B (en) * | 2015-12-24 | 2020-06-09 | 财团法人工业技术研究院 | Sensing chip |
| CN105890927B (en) * | 2016-06-06 | 2019-05-07 | 深圳小孚医疗科技有限公司 | A kind of urine analysis system and its urinalysis method |
| CN108535472B (en) * | 2018-02-27 | 2021-09-24 | 上海艾瑞德生物科技有限公司 | Detection test strip capable of remarkably improving lateral flow immunochromatography |
| CN109991346A (en) * | 2019-04-18 | 2019-07-09 | 南京大学 | A kind of micro-fluidic Ultraviolet Oxidation device for organic nitrogen analysis |
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