CA1131932A - Analyzer apparatus featuring a simplified incubator - Google Patents
Analyzer apparatus featuring a simplified incubatorInfo
- Publication number
- CA1131932A CA1131932A CA364,404A CA364404A CA1131932A CA 1131932 A CA1131932 A CA 1131932A CA 364404 A CA364404 A CA 364404A CA 1131932 A CA1131932 A CA 1131932A
- Authority
- CA
- Canada
- Prior art keywords
- elements
- incubator
- test elements
- sample
- test
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- 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
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
-
- 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
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00039—Transport arrangements specific to flat sample substrates, e.g. pusher blade
-
- 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
- G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
- G01N2035/00099—Characterised by type of test elements
- G01N2035/00138—Slides
-
- 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
- G01N2035/00346—Heating or cooling arrangements
- G01N2035/00356—Holding samples at elevated temperature (incubation)
- G01N2035/00376—Conductive heating, e.g. heated plates
Abstract
ANALYZER APPARATUS FEATURING A SAMPLIFIED
INCUBATOR
Abstract An analyzer apparatus and a method or analyte detection are disclosed, the apparatus featuring an in-cubator and detecting means. The incubator is designed to guide a sequence of test elements therethrough while each element is in contact with adjacent elements. Optional means are included for urging the elements to move through the incubator to the detecting means.
INCUBATOR
Abstract An analyzer apparatus and a method or analyte detection are disclosed, the apparatus featuring an in-cubator and detecting means. The incubator is designed to guide a sequence of test elements therethrough while each element is in contact with adjacent elements. Optional means are included for urging the elements to move through the incubator to the detecting means.
Description
113~932 ANALYZER APPA~ATUS FEATURING A SIMPLIFIED
INCUBATOR
Field of the Invention This lnventlon relates to apparatus and a de-tection method partlcularly adapted ror the chemlcal an-alysis of substances, known as analytes, ln llqulds.
Background of the Inventlon Numerous radlometrlc analyzers of blood have been disclosed, most of whlch lnvolve ralrly comple~ apparatus lO deslgned to provide automated handllng or blood samples and test elements. Such handllng usually lncIuded meterlng or ~i~mples onto the elements, lncubation and detectlon Or the resultlng radlometrlc changes. Examples Or such analyzers are descrlbed in, e.g., U.S. Patent No. 4,152,390, lssued on 15 May 1, 1979.
To obtaln a productlve through-put rate, lt 18 desirable that such analyzers accommodate a backlog Or the test elements. Usually the backlog ls temporarlly stored ln the lncubator durlng the development stage. Some analyzers 20 feature rotatlng clrcular lncubators whlch lnvolve the rollow-lng complexltles: Unless compllcated equlpment ls added to load the lncubator *lthout stopplng lt, such lncubators must lnclude motors, geàrlng and the llke to stop the lncubator ror loadlng and unloading, and to restart lt. So that test
INCUBATOR
Field of the Invention This lnventlon relates to apparatus and a de-tection method partlcularly adapted ror the chemlcal an-alysis of substances, known as analytes, ln llqulds.
Background of the Inventlon Numerous radlometrlc analyzers of blood have been disclosed, most of whlch lnvolve ralrly comple~ apparatus lO deslgned to provide automated handllng or blood samples and test elements. Such handllng usually lncIuded meterlng or ~i~mples onto the elements, lncubation and detectlon Or the resultlng radlometrlc changes. Examples Or such analyzers are descrlbed in, e.g., U.S. Patent No. 4,152,390, lssued on 15 May 1, 1979.
To obtaln a productlve through-put rate, lt 18 desirable that such analyzers accommodate a backlog Or the test elements. Usually the backlog ls temporarlly stored ln the lncubator durlng the development stage. Some analyzers 20 feature rotatlng clrcular lncubators whlch lnvolve the rollow-lng complexltles: Unless compllcated equlpment ls added to load the lncubator *lthout stopplng lt, such lncubators must lnclude motors, geàrlng and the llke to stop the lncubator ror loadlng and unloading, and to restart lt. So that test
2, elements can be loaded ln any posltlon that becomes avallable ln the lncubator, each element's locatlon at a specirlc "address" ln the~rotatlng lncubator must be "remembered,~
entalllng computer tracklng or the element ror proper retrl-eval Or the element and reloading or the lncubator. Slnce 30 the load station ls rixed relatlve to the rotatlne lncubator, access to the lncubator ls llmlted to those lnstances when an empty lncubator posltlon appears at the load station.
; Flnally, an lncubator that rotates with respect to the remainlng apparatus must provide temperature control through 35 a coupllng system that accommodates relatlve movement, e.g., electrlc 811p rings. Although all these aspects Or the - rotatlng lncubator are well wlthln the sklll Or the artj~ they lncrease the cost and complexlty Or the lncubator, and weigh agalnst on-slte analysls, e.g., at the physlclan's orrlce.
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~` 113193Z
--2_ A ~urther di~iculty in designing such lncubators occurs because certain test chemistries produce gases which, 1~ carried over to the following test samples, would cause erroneous readings. For example, test elements that quanti~y levels of BUN usually produce ammonia. Examples Or such test elements are described in U.S. Patent No. 4,066,403, issued on January 3, 1978. Ammonia that ls lntended to create a color change only internally in lts test element can escape, in some instances. In the worst case, thls gas is carrled 10 as a contaminant to the next test element ln an lncubator.
At best, escaping gas represents analyte that wlll not be detected, posslbly resultlng ln a low readlng. Prlor to this lnventlon, the problem or contamination ~rom escaplng gas has been dealt with through the use o~ test element 15 covers and lncubator materials that absorb little o~ the gQB ln questlon.
Summary o~ the Invention This lnvention ls dlrected to apparatus ~or the analysis of liquids, a simpliried lncubator thereror, and a 20 method Or detecting analytes, that are capable o~ a pro-ductive through-put rate without the problems outllned above.
`More specifically, ln one aspect o~ the lnventlon there is provlded an lncubator ror apparatus that detects sample analyte responses ln generally ~lat test elements 25 havlng a ~lrst maJor surrace that includes a sample-con-~ taining portion, and one or more opposing support surraces.
;~ The incubator includes wall means ror a) de~lnlng a path between rirst and second locatlons and b) supporting the elements for movement along the path wlth each element ln
entalllng computer tracklng or the element ror proper retrl-eval Or the element and reloading or the lncubator. Slnce 30 the load station ls rixed relatlve to the rotatlne lncubator, access to the lncubator ls llmlted to those lnstances when an empty lncubator posltlon appears at the load station.
; Flnally, an lncubator that rotates with respect to the remainlng apparatus must provide temperature control through 35 a coupllng system that accommodates relatlve movement, e.g., electrlc 811p rings. Although all these aspects Or the - rotatlng lncubator are well wlthln the sklll Or the artj~ they lncrease the cost and complexlty Or the lncubator, and weigh agalnst on-slte analysls, e.g., at the physlclan's orrlce.
,' ' ' , " :.' ` ` ' . ~
~` 113193Z
--2_ A ~urther di~iculty in designing such lncubators occurs because certain test chemistries produce gases which, 1~ carried over to the following test samples, would cause erroneous readings. For example, test elements that quanti~y levels of BUN usually produce ammonia. Examples Or such test elements are described in U.S. Patent No. 4,066,403, issued on January 3, 1978. Ammonia that ls lntended to create a color change only internally in lts test element can escape, in some instances. In the worst case, thls gas is carrled 10 as a contaminant to the next test element ln an lncubator.
At best, escaping gas represents analyte that wlll not be detected, posslbly resultlng ln a low readlng. Prlor to this lnventlon, the problem or contamination ~rom escaplng gas has been dealt with through the use o~ test element 15 covers and lncubator materials that absorb little o~ the gQB ln questlon.
Summary o~ the Invention This lnvention ls dlrected to apparatus ~or the analysis of liquids, a simpliried lncubator thereror, and a 20 method Or detecting analytes, that are capable o~ a pro-ductive through-put rate without the problems outllned above.
`More specifically, ln one aspect o~ the lnventlon there is provlded an lncubator ror apparatus that detects sample analyte responses ln generally ~lat test elements 25 havlng a ~lrst maJor surrace that includes a sample-con-~ taining portion, and one or more opposing support surraces.
;~ The incubator includes wall means ror a) de~lnlng a path between rirst and second locatlons and b) supporting the elements for movement along the path wlth each element ln
3 contact wlth the ad~acent elements and wlth the sample-contalnlng portlon o~ all but one element covered by the opposlng support sur~aces of an ad~acent element. Optlonal-ly, the lncubator ~urther lncludes means ~or maintalnlng the lncubator at a predetermlned temperature.
In another aspect Or the lnventlon, there ls provlded apparatus that lncludes the above-descrlbed lncuba-tor, means ~or loading test elements lnto the lncubator at the above-noted ~lrst locatlon, means ~or unloadlng the test elements ~rom the lncubator at the second location, and .
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~131932 means ad~acent the second locatlon for detectlng the de-tectable response o~ the test elements.
In a further aspect Or the lnvention, the lncuba-tor comprlses wall means deflnlng a stationary, generally elongated chamber and at the above-noted flrst locatlon, an access aperture permltting lntroductlon of elements lnto the chamber, the chamber belng adapted to support a plurallty of the test elements ln a conflguratlon whereln each element ls ln contact wlth ad~acent elements.
In yet another aspect Or the lnventlon, the ln-cubator lncludes gulde means ror guldlng a plurallty Or such test elements ln succession rrOm the rlrst locatlon to the second locatlon wlth the surraces Or ad~acent elements ln an opposed, contactlng relatlon; loadlng means belng dlsposed to orlent elements ln the gulde means such that the sample-containing portlon of all ~ut one element ls covered by the opposlng surfaces Or an ad~acent element.
The method Or the lnventlon provldes detectlon Or analytes by sequentlally placlng test elements contalnlng the sample llquld, lnto a conflguratlon whereln each element ls ln contact wlth ad~acent elements and the sample-contaln-lng portlon Or all but one Or the elements ls covered by one or more support surfaces Or one Or the adJacent elements, detectlng a response ln the elements ln the same sequence as they are placed ln the conrlguratlon, and removlng the test elements rrom the conflguratlon elther before or arter the detectlon step.
Thus, one advantage Or the present lnventlon ls that an analyzer ls provlded wlth a hi6h through-put, "tlme-lnde-pendent access" lncubabor that does not requlre the motors andcontrols Or rotatlng lncubators. Prererably thls 18 achleved by making the lncubator statlonary wlth respect to the rest Or the analyzer.
; A related advantage Or the lnventlon ls that an analyzer ls provlded wlth an lncubator that avolds the nec-esslty rOr sophlstlcated addresslng systems to recall the patlent ldentlty assoclated wlth each of several lncubator locatlons.
Another advantage Or the lnventlon ls that an - . - ~ . ~
.. ~
_4 analyzer incubator ls provlded that arranges the test eie-ments so that the elements themselves ~unctlon to prevent gas escape such as would cause a low readlng or a gas cross-over or contamination from one element to another.
Still another advantage o~ the lnventlon ls that 'he lncubator Or the analyzer ls drastically reduced ln size.
Other features and advantages wlll become apparent upon reference to the followlng Descrlptlon or the Pre~erred 10 ~mbodiments when read ln llght o~ the attached drawings.
~rier DescrlPtion o~ the Drawln~s Fig. 1 ls a ~ragmentary, partially schematlc, partially broken away perspectlve vlew o~ an analyzer con-structed in accordance with the lnventlon;
Fig. 2 is a rragmentary perspectlve vlew or an assembled analyzer;
Flg. 3 ls a ~ragmentary sectlonal vlew o~ the lncubator of the analyzer, as seen from the eJector element slde;
Flg. 4 ls a ~ragmentary perspectlve vlew o~ the analyzer, ln which the meterlng statlon has been removed ~or clarlty;
Flg. 5 is a plan vlew o~ the analyzer;
Flg. 6 ls a fragmentary perspectl~e vlew o~ part 25 of the mechanism by whlch the urging means o~ the lncubator $s connected to the loadlng means; `
Fig. 7 ls an elevational vlew of the eJector element of the unloadlng means, one rlange of the spool belng removed ~or clarlty;
3 Flg. 8 is a sectional vlew taken generally along the llne 8-8 o~ Fig. 7;
Fig. 9 is a perspectlve vlew of the e~ector ele-ment; and Flg. 10 ls a sectlonal vlew ~lmllar to that o~
35 Flg. 3, but lllustratlng an alternate embodlment.
Descrlptlon o~ the Preferred Embodlments The incubator of thls lnventlon is capable o~
measurlng a ~arlety o~ analytes o~ llqulds, partlcularly those of blological llqulds. This ls accompllshed con-~ .,.
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,; . ~
1~3~32 venlently through the use of generally flat test elements Eand E', Fig. 3, that reature a first ma~or surrace derlned by a sample-containing portion 14 mounted in a plastic frame member 15. Portion 14 in turn comprises one or more absorbent layers 17 on a transparent support 14'. The top surface Or layers 17 is exposed to receive a quantity Or liquid, such as a drop shown in dotted outline, Flg. 3. Opposite to the layers of portion 14 are the support surfaces Or the element, comprising the bottom surface 16 of frame member 15, and the bottom surface 19 of support 14' exposed through wlndow 18 of frame member 15.
In an alternatlve embodlment, support surfaces 16 and 19 are all one surface (not shown) formed as a single unitary support wherein the support 14' is an extension of frame member 15.
The structure of layers 17 permits them to contain liquid that is deposited thereon. Layers 17 preferably are constructed in the manner described ln U.S. Patent Nos.
3,992,158, issued November 16, 1976, and 4,066,403, lssued January 3, 1978. Deposited liquld spreads into the layers where the reaction takes place that generates a detectable change.
Side edges 21 and 23, Fig. 1, deflne the wldth and length, respectively, of the elements. Such dlmensions are sub~ect to variation, as deslred. The thickness of the various layers of elements E has been exaggerated for clar-ity in Fig. 3. In practice, the total thickness Or element E is only about 1 mm.
U.S. Patent No. 4,169,751, issued on October 2, 1979, 3 discloses a fully comparable and use~ul test element whereln test portion 14 ls staked to a support rrame apertured to allow a llquld drop to permeate lnto portlon 14.
~ lements such as elements E and E' are-preferably processed by spotting wlth a drop Or the ll~uld under an-aIysis, lncubatlng to develop a detectable response that lsproportional to the concentration Or the analyte under " :' :
:: . . ..
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:
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113~32 study, and detectlng the response. In ~ pre~erred ~orm, the response ls detected by re~lectlve scanning Or the element through window lB and the transparent support.
Thus, the detection is pre~erably accompllshed 5 radiometrically, but any ~orm Or detection ls possible uslng this invention, lncludlng potentiometric detectlon, provlded that the detecting means, hereina~ter described ln detall, ls sultably modified. As used hereln, "radiometric" and its derivatives are understood to lnclude colorlmetrlc as well as fluorlmetriC species.
The embodlments herelnarter descrlbed refer to blood serum as the prererred liquld under analysls. In additlon, other analyte-containing liquids can be so an-alyzed, lncluding lndustrlal llqulds contalnlng non-blolog-lcal analytes.
Descriptlve terms such as "above", "below", "down-ward", "botto~most" and the like as used hereln refer to orlen-thtlons during use of the analyzer. The term "tlme-lndependent access" as applled to the lncubator refers to lts flexlbllity ln accepting another test element at any tlme, rather than only when the next avallable one of several dlscrete lncubator posl-tlons 18 allgned wlth the means ~or loadlng the lncubator.
~ eferrlng to Figs. 1-3 and Fig. l ln partlcular, an analyzer 20 constructed ln accordance wlth the lnventlon comprises a rrame 22 that mounts a test element loading means 30, a metering station 40, an incubator 5~, a radlo-meter 110 as the detectlng means, and test element unloading means 130. Loading means 30 comprises a plat~orm 32 which is optionally preheated, a pusher rlnger 34 that proJects up 3 through a slot 35 ln the plat~orm and a handlo 36 on whlch ~lnger 34 is mounted. Platrorm 32 ls preferably provlded wlth conventlonal electrical heatlng elements, not shown, and is dlsposed between shoulders 38 that, in cooperatlon wlth rlnger 34, guide test elements E and E' ln the di-rectlon o~ arrows 39 toward lncubator 5Q.
Meterlng station 40 can lncorporate any meterlngdevice for depositing a drop Or test liquld onto element E
or E' as lt rests on plat~orm 32. A pre~erred devlce ls a pipette 42 mounted in a holder 44 so that tlp 46 o~ the ... .
~, -,..,-: ' - - ,, ,. .
- - ~: .. ; . : . , :
~; ,'" ~ ~ `: ;
"` 113~932 pipette ls dlsposed closely adJacent and directly above portlon 14 of the test elements. Prererably, tip 46 ls dlsposable to prevent sample contamlnatlon Or the remalnder Or plpette 42.
Alternatlvely, statlon 40 can be omltted and the liquld added to the elements by any other instrument, not shown, prior to belng placed on platrorm 32.
In accordance with one aspect Or the lnvention, an incubator 50 ls provided ln analyzer 20 with walls 52, Flg.
3, that derine a generally elongated chamber 54. To permlt test elements E and E' to be lntrod~ced lnto chamber 54 at a first location 56, wall 52 ls provlded wlth an access aper-ture 55, Flgs. 3 and 4, ~dJacent platform 32. Ch~mber 54 also lncludes an element-readlng locatlon 58. Wlthln the chamber the elements rollow path 57 from rlrst locatlon 56 to locatlon 58, along the longltudlnal axls 60 Or the cham-ber. Walls 52 preferably are shaped to form a gulde means or a rectangular chute the dimenslons or whlch wlll accom-modate the test elements ln a slldlng rlt, wlth element 20 portlons 14 and 15 extendlng general}y transverse to a~ls 60. Therefore, each test element ln chamber 54 necessarlly contacts the ad~acent elements such that each support surrace 16 Or frame member 15, as well as or the support surrace 19 support 14', covers the sample-contalnlng portlon 14 Or 2~ the element precedlng lt. More speclrlcally, the length Or the chamber between locatlons 58 and 56 wlll ac~ommodate a contlnuous traln o~ "n" elements, n belng equal to three ln the embodlment Or Flg. 4. The element at locatlon 58 ls Or course the rlrst element o~ the traln to have been lnserted 30 by loading means 30, and element E' ls the last olement or whlch portlon 14 ls not covered by the adJacent test elements.
Prererably, chamber 54 ls dlsposed vertlcally, whereby the conrlguratlon Or the incubated elements ls tbat a contlguous stack. Gravlty ls usually surrlclent ln ~ 35 such an embodlment to move the elements rrom locatlon 56 to ; lo¢atlon 58. Also pre~erably, lncubator 50 ls statlonary wlth respect to the other non-moving parts cr the analyzer.
A cover 62 18 prererably lncluded ~or element E', ; Flgs. 1 and 3, slnce portlon 14 or element E' ls not otherwlse - . " - .
_ covered. Because the cover has to be withdrawn lr and when an add~tlonal element ls added to chamber 54, lt ls mounted to reclprocate, arrows 64, wlthln chamber 54 from a posltlon above locatlon 56 to a posltlon ln contact with elther the 5 bottom of the chamber at locatlon 58 or the elements E ln the chamber. Preferably cover 62 ls secured to a rod 66, Flg. l, that ln turn ls secured vla connector means 67 to handle 36. Referring to Figs. 2 and 4-6, connector means 67 comprises crank 72, plnloned at end 70 to rod 66. Crank 10 72 is J-shaped, the mld-portlon 74 belng Journalled to rrame 22 as a plvot polnt. End 76 Or shorter leg 78 Or cranlc 72 ls then ~ournalled to a llnk B0 that reclprocates vertically on the frame. One end 82 Or link 80 is connected to crank 72, and the other end 84 rides on a canunlng bar ~6 provided 15 at one end 88 with a camming surrace 90, Figs. 4 and 6.
Llnk 80 ls conflned to vertlcal movement by reason Or end 84 belng ~ournalled to llnk arm 91, Flgs. 4 and 5, Or rrame 22.
The opposlte end 92 Or bar ~6 ls Journalled to handle 36, Fig. 6, and the entlre bar 86 slldes, arrows 94, wlthln a V-20 shaped groove 96 Or the rrame. The opposlte end 98 orhandle 36 can be gulded between two plates 100 rOr rotatlonal stabillty.
Optlonally, pusher rlnger 34 ls mounted to rotate ln the dlrectlon Or arrows 102 on handle 36, wlth a torslon 25 sprlng, not shown, blaslng the rlnger back ln the other dlrectlon. A sloplng cammlng surrace 104 on ~ln~er 34 permlts elements E to be lnserted by auxillary means whlch overrlde ~lnger 34.
;~ Pre~erably, cover 62 18 glven su~rlolent ~e~ght, 3 due to lt~ bulk, to ~erve as means ~or urglng elements E
through the chamber. That 18, when shaped as a platen, cover 62 serves to prevent element~ E rrOm lodglng agalnst the walls 52. However, the urglng capablllty Or cover 62 i5 not needed lr the ~paclng between ~alls 52 18 enlarged to prevent accldental lodglng o~ element~ E..
In an alternate embodlment, not ~hown, cover 62 ls omltted entlrely, ror example, ln those analyzers that test ror only those analytes that do not generate a gas as the detectable reagent a~d do not require a thermal cover.
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_g Radi~meter 110 ls disposed at or adJacent to locatlon 58, to read the bottommost element E ln the cham-ber. Useful radiometers lnclude colorimetric and ~luorl-metric radiometers such as are conventlonal ln the art. A
preferred rorm is a re~lectometer comprlslng a llght source 112 located generally underneath platrorm 32, Flg. 1, allgned at 45 to axis 60 to send llght vla radlation gulde means 115, Flg. 1 through passageway 113, Flg. 3, ln the dlrectlon or arrow 114 to the vlewlng wlndow 1~ or the bottommost element. A dl~ractlon gratlng 116, Flg. 1, adapted to produce a spectrum Or ~rom about 340 to about 700 nm wave-lengths, ls dlsposed ln the path o~ beam 120, and photo-diodes or detectors 118 each are posltloned to detect a particular wavelength of spectral beams 119, passed through a lens~ not shown, QS 16 conventlonal. m e dl~fuse component of the reflected beam 120 i8 collected vi~ radiation gulde means 122, Flg. 1, through a passageway 121 allgned wlth axls 60, Fig. 3. Grating 116 ls preferably telecentrically located, l.e., at the focal polnt of lens 122. m e slgnals generated by detectors 118 are converted via an flnalog to dlgital convertor coupled to a conventional computer such as a micro-processor, not shown, to a concentration value based upon calibration values that have been m~nually keyed lnto the mlcro-processor. Optionally, the micro-processor al80 includes a t~ing device, not shown, that computes how long each test element i6 incubated prior to initiatrng the readlng cycle.
Other radiometers are use~ul wlth the lncubatoi descrlbed above. As one alternatlve, not shown~ the plane derlned by llght beams 114 and 120 can be perpendlcular to the plane deflned by the spectral beams 119, wlth source 112 disposed under surrace 133 discussed below.
To sequentlally unload lncubator 50 on a ~irst-in, ~irst-out basls, unloadlng means 130 comprises eJector element 132 dlsposed at locatlon 58 o~ chamber 54 to remove the read element E ~rom the stack, across support surrace 133 ln the dlrectlon Or arrow 134 out through aperture 136, Flgs. 2 and 4. Element 132 ls an elongated blade havlng a , , ~ . , ' .:' ';
.: ~
~131~332 pusher end 138, a top surf~ce 139 and underAurrace 140, Figs. 7-9. me portlon of under6urface 140 ad~acent to end 138 ls pre~erably provlded wlth a whlte rererence coatlng or standard surrace 142 and a dark rererence coatlng or surrace 144, to calibrate the analyzer. Alternatlvely, the dark ~^ference reading is obtalnable by uslng a shutter or by extlnguishing the llght source, and the whlte rererence readlng ls obtalnable by a reed-back dlode, not shown, that monltors or controls the intenslty or source 112.
The portlon 148 Or undersurrace 140 Or element 132 that ls dlstal to end 138 ls aecured by means auch as screws to a cable 150 that ls wound upon a spool 152, Flg. 8.
Rotatlon Or the spool serves to reclprocate eJector element 132 ln the directlon Or arrows 154, Flg. 1, as dlrected by a conventlonal A.C. reverslble motor 156. One or more sensors 158, conventlonal opto-electrlc swltches that cooperate wlth angle members 160, serve to control the operatlon o~ the motor. For more acc~rate control over the extent Or trQvel o~
e~ector ele~ent 1~2, for example as 16 deslrable when radlometer 110 is located outslde of the ~ncubator as descrlbed herelnafter, a stepper motor ls provlded ~n place of motor 56, operatively connected to element 132 by a rack and pinion, whereln the rack is on the element 132.
Alternatlvely, end 138 or eJector element 132 can 25 be blrurcated, not shown, ~o that lt bears only on the edges ~; Or the test elements.
The dlmenslons ror the parts descrlbed are not critlcal and depend upon several ractors, or whlch the test element dlmenslons are a ma~or ~actor. For example, ~or 30 test elements that are about 24 mm by 28 mm, the walls 52 sre set apart a distance that provldes about 0.25 mm total clearance Or the test elements ror each o~ the alngle slde edges 23 and 21 Or the elements, to permlt the slidlng ~lt the elements transverse to the longltudlnal a~ls Or the 35 lncubator. Alternatlvely, other slzes and/or shapes ~or the test elements dlctate approprlate alteratlons ln the slze or shape Or the chamber.
;~
.'~ ! 1, ' , , -~ 1131~33Z
Regardless o~ the size Or the test elements, rOr pr~per alignment Or the vlewlng area o~ the element wlth the ~ad~ometer 110, at locatlon 58 of the incubator, the outslde dimenslons of the test element prefer~bly are malntalned with 5 close tolerances, l.e., no greater than ~ 0.25 mm. Alter-natively, one of slde walls 52 o~ lncubator 50, and prer-erably the slde wall 52'~, Flg. 4, ls used as a rererence surface agalnst whlch the test elements are blased when they reach end portlon 58 Or the lncubator. To 80 blas the test 10 elements, prererably the top surrace 139, Fig. 7, o~ eJector element 132 is provlded wlth a rrlctlon material, not shown, that engages the ne~t test element to be vlewed as the e~ector element ls belng wlthdrawn rrom the lncubator prlor ~ the next readlng by the radlometer. The rrlctlon mate-15 rlal serves to pull the test element up agalnst wall 52'.Small pads or urethane are representatlve Or userul rrlctlon materlals.
If such rrlctlon materlal ls used, the e~ector element ls preferably rully extended lnto the lncubator when 20 the rlrst test element E is lnserted lnto the lncubator.
The test element E also ls prererably blased by a movable flnger, not shown, in the orthogonal dlrectlon agalnst one Or the walls 52, Flg. 3, that ls perpendlcular to wall 52', not shown. Such rlnger is llnked to the movement Or eJector 25 element 132 so as to clear chamber 54 when the unloadlng means ls actlvated.
The operatlon Or the analyzer wlll be readlly apparent rrom *he precedlng discusslon. A test element E ls deposited on platrorm 32 where lt 15 preheated and spotted 3 wlth a drop Or llquld by the meterlng statlon 40. Any slze drop ls userul, although lt has been round that ror test elements E descrlbed, 10 ~1 ls a prererred volume. Follow-ing the meterlng operatlon, the operator pushes handle 36 towards incubator 5Q, causlng pusher rlnger 34 to move 35 element E towards chamber 54. At the same time, cammlng bar 86 causes llnk Bo to move rod 66 upwardly, clearing cover 62 rrom chamber 54. Element E ls thus placed lnto the chamber, and the return or handle 36 to its lnitlal posltlon causes bar B6 to clear llnk 80 and thus cover 62 ralls onto ;
, . ~ . . . .....
. , :' ~ -113~32 element E at locatlon 5~ Or chamber 54. A perlo~ Or ln-cubation follows, durlng which the color density or other response, e.g., fluorimetrlc response, develops. Durlng thls tlme, addltional élements E can be spotted wlth llquld and sequentlally placed lnto chamber 54 ln like manner. Any gas that mlght otherwise evolve ~rom portlon 14 Or element E
is trapped and conflned by the coverlng relatlonshlp o~ the test element above lt, or by cover 62 lr the element ls last element E'. The resultlng pressure tends to retaln the gas wlthln the test element~ Eventually, and ln the same se-quence ln whlch the test elements are spotted, they are read by radlometer 110 and the slgnals are converted to a oon-centratlon read-out ror recordlng by the operator. Arter detectlon by the radlometer, the elements are eJected or removed by eJector element 132. Each tlme e~e¢tor element 132 ls activated to remove a test element, coatlng 142 and then coatlng 144, lf present, are read by the radlometer to malntaln proper callbratlon of the analyzer.
Optlonally, lncubator 50 lncludes temperature control means for malntalnlng walls 52 at a constant, prede-termlned, elevated temperature, ror example, 37C. A varlety of conventlonal heatlng technlques are useful. For e~ample, electrlcal elements 169, Flg. 3, are mountable wlthln or ln contact with walls 52~ In such an embodlment, cover 62 ls preferably a conductlve metal so as to be passlvely heated by walls 52 or actlvely heated by electrlcal elements mount-~- ed thereln. Such temperature control means are prererred when the detected analyte 18 markedly v~arlable with temper-ature, ror e~ample, when the analyte i8 an enzyme.
;v An addltlonal optlonal ~eature 18 a nozzle 170, Flg. 3, mounted at locatlon 58 ror dlrectlng an alr stream ~ in the dlrectlon Or arrows 172 along the readlng race o~ the ;; bottommost test element E. Such a stream removes any molsture that mlght condense on the readlng race as a result Or evolved water vapor. Nozzle 170 ls supplled, e.g., wlth alr vla a passageway 174 fed ~rom the heated portlons or wall 52. A transparent plate 178 ls disposed ~ar enough away ~rom the support surraces Or elements E 80 that a ,: . .. .
~ : . . . . - ~ -, ~.~' ' ~13193Z
Coanda alr ~low e~fect ls created as the alr stream attaches to the test element E being vlewed.
In Flg. 10, the incu~ator ls deplcted alterna-tlvely as comprislng a chamber ortented horlzontally rather than vertlcally as in the previous embodiment. Parts slml-lar to those prevlously described bear the same rererence numeral to whlch a distlngulshlng surrlx "a~ ls attached.
Thus, the analyzer comprises an lncubator 50a havlng an elongated chamber 54a wlth a longltudinal axls 60a, and a radiometer as before. Test element6 E are each lnserted lnto chamber 54a ln contact wlth the next adJacent element wlth frame members 15a extendlng generally transverse to axls 60a, also as before. However, the elements E are now lnserted through a vertlcal aperture 55a, Qhown ln dashed l~nes, and are malntalned generally vertlcally as they move from locatlon 56a to locatlon 58a. The means urglng the elements to move ln thls fashlon is a cover 62a on a rod 66a blased by a sprlng 210 to move the cover towards locatlon 58a. Rod 66a ls caused to reclprocate ln cooperatlon wlth the loading means by the ~ame mechanlsm as ls descrlbed ~or the previous embodiment, except that end 84 of llnk 80 ls posltively Journalled to end 8B Or bar 86. E~ectlon of read elements occurs as before.
The parts Or the lncubator and other de6crlbed components are metalllc or plastlc as determlned by con-ventlonal deslgn conslderatlons. If walls 52 and portlon 212 of locatlon 58, Flg. 3, are to be heated, then pref-erably they are metalllc, such as copper, whereas the portlons derlnlng passageways 113 and 121 are pro~erably plagtlc to prevent heat 1088.
In yet another embodlment, not shown, the radlo-meter ls dlsposed outside Or the lncubator, to detect from below support surface 133, t~e response of each Bllde separately after lt ls eJecte~` from the lncubator. Such an ; 35 arrangement of the detectlng means ls partlcularly preferred for test elements that are BO transparent as to ~llow the adJacent elements to be sensed lf the radiometer ls located .
- . .. . .
.- , ~31932 at the bottom of the lncubator as prevlously descrlbed.
In such an embodlment, a backing surface ls dl~posed above the support surfsce, and preferably includes a whlte reference coating that ls scanned when a test element 16 not present. me radlometer dlsposed out61de of the incubator chamber dlrects a llght beam up to the readable support portion of the element, at wlndow 18 as the element ls e~ected along path 134.
The advantages of the analyzer of the lnventlon wlll be readlly apparent from the precedlng discu6610n.
Tlme-independent access of test elements 18 po661ble wlth a rapld through-put rate. No motor, gear6, controls or rotation-permlttlng heatlng control6 are necessary for the lncubator ltself, because the lncubator 18 statlonary rather l~ than rotatlng. No addresslng or computer tracklng of addresses 18 necessary for proper retrleval of the elements ln the lncubator other than the conventlonal lndexlng devlce descrlbed above. Because no ~pace 18 requlred between test elements, the slze of the lncubator 18 reduced to a mlnlmum.
Flnally, control of evolved gases ls provlded by the arrange-ment of the test elements themselves, ellminatlng the need for speclal parts ln the lncubator chamber. The result 16 an analyzer that ls partlcularly useful at, e.g., a doctor's offlce.
2~ The lnventlon has been descrlbed ln de~all wlthpartlcular reference to certaln preferred embod;ments thereof, but lt wlll be understood that variatlons and modlflcatlon6 csn be efrected ~lthln the ~plrlt and ~cope of the lnventlon.
.~
' . . . ... . .
.: :
.
.
In another aspect Or the lnventlon, there ls provlded apparatus that lncludes the above-descrlbed lncuba-tor, means ~or loading test elements lnto the lncubator at the above-noted ~lrst locatlon, means ~or unloadlng the test elements ~rom the lncubator at the second location, and .
. :. . ...
,: '`,' ; ' ,~ ~ ' ...
., . ~ . .
, ~ :
~131932 means ad~acent the second locatlon for detectlng the de-tectable response o~ the test elements.
In a further aspect Or the lnvention, the lncuba-tor comprlses wall means deflnlng a stationary, generally elongated chamber and at the above-noted flrst locatlon, an access aperture permltting lntroductlon of elements lnto the chamber, the chamber belng adapted to support a plurallty of the test elements ln a conflguratlon whereln each element ls ln contact wlth ad~acent elements.
In yet another aspect Or the lnventlon, the ln-cubator lncludes gulde means ror guldlng a plurallty Or such test elements ln succession rrOm the rlrst locatlon to the second locatlon wlth the surraces Or ad~acent elements ln an opposed, contactlng relatlon; loadlng means belng dlsposed to orlent elements ln the gulde means such that the sample-containing portlon of all ~ut one element ls covered by the opposlng surfaces Or an ad~acent element.
The method Or the lnventlon provldes detectlon Or analytes by sequentlally placlng test elements contalnlng the sample llquld, lnto a conflguratlon whereln each element ls ln contact wlth ad~acent elements and the sample-contaln-lng portlon Or all but one Or the elements ls covered by one or more support surfaces Or one Or the adJacent elements, detectlng a response ln the elements ln the same sequence as they are placed ln the conrlguratlon, and removlng the test elements rrom the conflguratlon elther before or arter the detectlon step.
Thus, one advantage Or the present lnventlon ls that an analyzer ls provlded wlth a hi6h through-put, "tlme-lnde-pendent access" lncubabor that does not requlre the motors andcontrols Or rotatlng lncubators. Prererably thls 18 achleved by making the lncubator statlonary wlth respect to the rest Or the analyzer.
; A related advantage Or the lnventlon ls that an analyzer ls provlded wlth an lncubator that avolds the nec-esslty rOr sophlstlcated addresslng systems to recall the patlent ldentlty assoclated wlth each of several lncubator locatlons.
Another advantage Or the lnventlon ls that an - . - ~ . ~
.. ~
_4 analyzer incubator ls provlded that arranges the test eie-ments so that the elements themselves ~unctlon to prevent gas escape such as would cause a low readlng or a gas cross-over or contamination from one element to another.
Still another advantage o~ the lnventlon ls that 'he lncubator Or the analyzer ls drastically reduced ln size.
Other features and advantages wlll become apparent upon reference to the followlng Descrlptlon or the Pre~erred 10 ~mbodiments when read ln llght o~ the attached drawings.
~rier DescrlPtion o~ the Drawln~s Fig. 1 ls a ~ragmentary, partially schematlc, partially broken away perspectlve vlew o~ an analyzer con-structed in accordance with the lnventlon;
Fig. 2 is a rragmentary perspectlve vlew or an assembled analyzer;
Flg. 3 ls a ~ragmentary sectlonal vlew o~ the lncubator of the analyzer, as seen from the eJector element slde;
Flg. 4 ls a ~ragmentary perspectlve vlew o~ the analyzer, ln which the meterlng statlon has been removed ~or clarlty;
Flg. 5 is a plan vlew o~ the analyzer;
Flg. 6 ls a fragmentary perspectl~e vlew o~ part 25 of the mechanism by whlch the urging means o~ the lncubator $s connected to the loadlng means; `
Fig. 7 ls an elevational vlew of the eJector element of the unloadlng means, one rlange of the spool belng removed ~or clarlty;
3 Flg. 8 is a sectional vlew taken generally along the llne 8-8 o~ Fig. 7;
Fig. 9 is a perspectlve vlew of the e~ector ele-ment; and Flg. 10 ls a sectlonal vlew ~lmllar to that o~
35 Flg. 3, but lllustratlng an alternate embodlment.
Descrlptlon o~ the Preferred Embodlments The incubator of thls lnventlon is capable o~
measurlng a ~arlety o~ analytes o~ llqulds, partlcularly those of blological llqulds. This ls accompllshed con-~ .,.
.
,; . ~
1~3~32 venlently through the use of generally flat test elements Eand E', Fig. 3, that reature a first ma~or surrace derlned by a sample-containing portion 14 mounted in a plastic frame member 15. Portion 14 in turn comprises one or more absorbent layers 17 on a transparent support 14'. The top surface Or layers 17 is exposed to receive a quantity Or liquid, such as a drop shown in dotted outline, Flg. 3. Opposite to the layers of portion 14 are the support surfaces Or the element, comprising the bottom surface 16 of frame member 15, and the bottom surface 19 of support 14' exposed through wlndow 18 of frame member 15.
In an alternatlve embodlment, support surfaces 16 and 19 are all one surface (not shown) formed as a single unitary support wherein the support 14' is an extension of frame member 15.
The structure of layers 17 permits them to contain liquid that is deposited thereon. Layers 17 preferably are constructed in the manner described ln U.S. Patent Nos.
3,992,158, issued November 16, 1976, and 4,066,403, lssued January 3, 1978. Deposited liquld spreads into the layers where the reaction takes place that generates a detectable change.
Side edges 21 and 23, Fig. 1, deflne the wldth and length, respectively, of the elements. Such dlmensions are sub~ect to variation, as deslred. The thickness of the various layers of elements E has been exaggerated for clar-ity in Fig. 3. In practice, the total thickness Or element E is only about 1 mm.
U.S. Patent No. 4,169,751, issued on October 2, 1979, 3 discloses a fully comparable and use~ul test element whereln test portion 14 ls staked to a support rrame apertured to allow a llquld drop to permeate lnto portlon 14.
~ lements such as elements E and E' are-preferably processed by spotting wlth a drop Or the ll~uld under an-aIysis, lncubatlng to develop a detectable response that lsproportional to the concentration Or the analyte under " :' :
:: . . ..
.
:
~ .
113~32 study, and detectlng the response. In ~ pre~erred ~orm, the response ls detected by re~lectlve scanning Or the element through window lB and the transparent support.
Thus, the detection is pre~erably accompllshed 5 radiometrically, but any ~orm Or detection ls possible uslng this invention, lncludlng potentiometric detectlon, provlded that the detecting means, hereina~ter described ln detall, ls sultably modified. As used hereln, "radiometric" and its derivatives are understood to lnclude colorlmetrlc as well as fluorlmetriC species.
The embodlments herelnarter descrlbed refer to blood serum as the prererred liquld under analysls. In additlon, other analyte-containing liquids can be so an-alyzed, lncluding lndustrlal llqulds contalnlng non-blolog-lcal analytes.
Descriptlve terms such as "above", "below", "down-ward", "botto~most" and the like as used hereln refer to orlen-thtlons during use of the analyzer. The term "tlme-lndependent access" as applled to the lncubator refers to lts flexlbllity ln accepting another test element at any tlme, rather than only when the next avallable one of several dlscrete lncubator posl-tlons 18 allgned wlth the means ~or loadlng the lncubator.
~ eferrlng to Figs. 1-3 and Fig. l ln partlcular, an analyzer 20 constructed ln accordance wlth the lnventlon comprises a rrame 22 that mounts a test element loading means 30, a metering station 40, an incubator 5~, a radlo-meter 110 as the detectlng means, and test element unloading means 130. Loading means 30 comprises a plat~orm 32 which is optionally preheated, a pusher rlnger 34 that proJects up 3 through a slot 35 ln the plat~orm and a handlo 36 on whlch ~lnger 34 is mounted. Platrorm 32 ls preferably provlded wlth conventlonal electrical heatlng elements, not shown, and is dlsposed between shoulders 38 that, in cooperatlon wlth rlnger 34, guide test elements E and E' ln the di-rectlon o~ arrows 39 toward lncubator 5Q.
Meterlng station 40 can lncorporate any meterlngdevice for depositing a drop Or test liquld onto element E
or E' as lt rests on plat~orm 32. A pre~erred devlce ls a pipette 42 mounted in a holder 44 so that tlp 46 o~ the ... .
~, -,..,-: ' - - ,, ,. .
- - ~: .. ; . : . , :
~; ,'" ~ ~ `: ;
"` 113~932 pipette ls dlsposed closely adJacent and directly above portlon 14 of the test elements. Prererably, tip 46 ls dlsposable to prevent sample contamlnatlon Or the remalnder Or plpette 42.
Alternatlvely, statlon 40 can be omltted and the liquld added to the elements by any other instrument, not shown, prior to belng placed on platrorm 32.
In accordance with one aspect Or the lnvention, an incubator 50 ls provided ln analyzer 20 with walls 52, Flg.
3, that derine a generally elongated chamber 54. To permlt test elements E and E' to be lntrod~ced lnto chamber 54 at a first location 56, wall 52 ls provlded wlth an access aper-ture 55, Flgs. 3 and 4, ~dJacent platform 32. Ch~mber 54 also lncludes an element-readlng locatlon 58. Wlthln the chamber the elements rollow path 57 from rlrst locatlon 56 to locatlon 58, along the longltudlnal axls 60 Or the cham-ber. Walls 52 preferably are shaped to form a gulde means or a rectangular chute the dimenslons or whlch wlll accom-modate the test elements ln a slldlng rlt, wlth element 20 portlons 14 and 15 extendlng general}y transverse to a~ls 60. Therefore, each test element ln chamber 54 necessarlly contacts the ad~acent elements such that each support surrace 16 Or frame member 15, as well as or the support surrace 19 support 14', covers the sample-contalnlng portlon 14 Or 2~ the element precedlng lt. More speclrlcally, the length Or the chamber between locatlons 58 and 56 wlll ac~ommodate a contlnuous traln o~ "n" elements, n belng equal to three ln the embodlment Or Flg. 4. The element at locatlon 58 ls Or course the rlrst element o~ the traln to have been lnserted 30 by loading means 30, and element E' ls the last olement or whlch portlon 14 ls not covered by the adJacent test elements.
Prererably, chamber 54 ls dlsposed vertlcally, whereby the conrlguratlon Or the incubated elements ls tbat a contlguous stack. Gravlty ls usually surrlclent ln ~ 35 such an embodlment to move the elements rrom locatlon 56 to ; lo¢atlon 58. Also pre~erably, lncubator 50 ls statlonary wlth respect to the other non-moving parts cr the analyzer.
A cover 62 18 prererably lncluded ~or element E', ; Flgs. 1 and 3, slnce portlon 14 or element E' ls not otherwlse - . " - .
_ covered. Because the cover has to be withdrawn lr and when an add~tlonal element ls added to chamber 54, lt ls mounted to reclprocate, arrows 64, wlthln chamber 54 from a posltlon above locatlon 56 to a posltlon ln contact with elther the 5 bottom of the chamber at locatlon 58 or the elements E ln the chamber. Preferably cover 62 ls secured to a rod 66, Flg. l, that ln turn ls secured vla connector means 67 to handle 36. Referring to Figs. 2 and 4-6, connector means 67 comprises crank 72, plnloned at end 70 to rod 66. Crank 10 72 is J-shaped, the mld-portlon 74 belng Journalled to rrame 22 as a plvot polnt. End 76 Or shorter leg 78 Or cranlc 72 ls then ~ournalled to a llnk B0 that reclprocates vertically on the frame. One end 82 Or link 80 is connected to crank 72, and the other end 84 rides on a canunlng bar ~6 provided 15 at one end 88 with a camming surrace 90, Figs. 4 and 6.
Llnk 80 ls conflned to vertlcal movement by reason Or end 84 belng ~ournalled to llnk arm 91, Flgs. 4 and 5, Or rrame 22.
The opposlte end 92 Or bar ~6 ls Journalled to handle 36, Fig. 6, and the entlre bar 86 slldes, arrows 94, wlthln a V-20 shaped groove 96 Or the rrame. The opposlte end 98 orhandle 36 can be gulded between two plates 100 rOr rotatlonal stabillty.
Optlonally, pusher rlnger 34 ls mounted to rotate ln the dlrectlon Or arrows 102 on handle 36, wlth a torslon 25 sprlng, not shown, blaslng the rlnger back ln the other dlrectlon. A sloplng cammlng surrace 104 on ~ln~er 34 permlts elements E to be lnserted by auxillary means whlch overrlde ~lnger 34.
;~ Pre~erably, cover 62 18 glven su~rlolent ~e~ght, 3 due to lt~ bulk, to ~erve as means ~or urglng elements E
through the chamber. That 18, when shaped as a platen, cover 62 serves to prevent element~ E rrOm lodglng agalnst the walls 52. However, the urglng capablllty Or cover 62 i5 not needed lr the ~paclng between ~alls 52 18 enlarged to prevent accldental lodglng o~ element~ E..
In an alternate embodlment, not ~hown, cover 62 ls omltted entlrely, ror example, ln those analyzers that test ror only those analytes that do not generate a gas as the detectable reagent a~d do not require a thermal cover.
:; .
. , . , . ~ . . . , ^ --, , . . .
. , . : - , 113~93~
_g Radi~meter 110 ls disposed at or adJacent to locatlon 58, to read the bottommost element E ln the cham-ber. Useful radiometers lnclude colorimetric and ~luorl-metric radiometers such as are conventlonal ln the art. A
preferred rorm is a re~lectometer comprlslng a llght source 112 located generally underneath platrorm 32, Flg. 1, allgned at 45 to axis 60 to send llght vla radlation gulde means 115, Flg. 1 through passageway 113, Flg. 3, ln the dlrectlon or arrow 114 to the vlewlng wlndow 1~ or the bottommost element. A dl~ractlon gratlng 116, Flg. 1, adapted to produce a spectrum Or ~rom about 340 to about 700 nm wave-lengths, ls dlsposed ln the path o~ beam 120, and photo-diodes or detectors 118 each are posltloned to detect a particular wavelength of spectral beams 119, passed through a lens~ not shown, QS 16 conventlonal. m e dl~fuse component of the reflected beam 120 i8 collected vi~ radiation gulde means 122, Flg. 1, through a passageway 121 allgned wlth axls 60, Fig. 3. Grating 116 ls preferably telecentrically located, l.e., at the focal polnt of lens 122. m e slgnals generated by detectors 118 are converted via an flnalog to dlgital convertor coupled to a conventional computer such as a micro-processor, not shown, to a concentration value based upon calibration values that have been m~nually keyed lnto the mlcro-processor. Optionally, the micro-processor al80 includes a t~ing device, not shown, that computes how long each test element i6 incubated prior to initiatrng the readlng cycle.
Other radiometers are use~ul wlth the lncubatoi descrlbed above. As one alternatlve, not shown~ the plane derlned by llght beams 114 and 120 can be perpendlcular to the plane deflned by the spectral beams 119, wlth source 112 disposed under surrace 133 discussed below.
To sequentlally unload lncubator 50 on a ~irst-in, ~irst-out basls, unloadlng means 130 comprises eJector element 132 dlsposed at locatlon 58 o~ chamber 54 to remove the read element E ~rom the stack, across support surrace 133 ln the dlrectlon Or arrow 134 out through aperture 136, Flgs. 2 and 4. Element 132 ls an elongated blade havlng a , , ~ . , ' .:' ';
.: ~
~131~332 pusher end 138, a top surf~ce 139 and underAurrace 140, Figs. 7-9. me portlon of under6urface 140 ad~acent to end 138 ls pre~erably provlded wlth a whlte rererence coatlng or standard surrace 142 and a dark rererence coatlng or surrace 144, to calibrate the analyzer. Alternatlvely, the dark ~^ference reading is obtalnable by uslng a shutter or by extlnguishing the llght source, and the whlte rererence readlng ls obtalnable by a reed-back dlode, not shown, that monltors or controls the intenslty or source 112.
The portlon 148 Or undersurrace 140 Or element 132 that ls dlstal to end 138 ls aecured by means auch as screws to a cable 150 that ls wound upon a spool 152, Flg. 8.
Rotatlon Or the spool serves to reclprocate eJector element 132 ln the directlon Or arrows 154, Flg. 1, as dlrected by a conventlonal A.C. reverslble motor 156. One or more sensors 158, conventlonal opto-electrlc swltches that cooperate wlth angle members 160, serve to control the operatlon o~ the motor. For more acc~rate control over the extent Or trQvel o~
e~ector ele~ent 1~2, for example as 16 deslrable when radlometer 110 is located outslde of the ~ncubator as descrlbed herelnafter, a stepper motor ls provlded ~n place of motor 56, operatively connected to element 132 by a rack and pinion, whereln the rack is on the element 132.
Alternatlvely, end 138 or eJector element 132 can 25 be blrurcated, not shown, ~o that lt bears only on the edges ~; Or the test elements.
The dlmenslons ror the parts descrlbed are not critlcal and depend upon several ractors, or whlch the test element dlmenslons are a ma~or ~actor. For example, ~or 30 test elements that are about 24 mm by 28 mm, the walls 52 sre set apart a distance that provldes about 0.25 mm total clearance Or the test elements ror each o~ the alngle slde edges 23 and 21 Or the elements, to permlt the slidlng ~lt the elements transverse to the longltudlnal a~ls Or the 35 lncubator. Alternatlvely, other slzes and/or shapes ~or the test elements dlctate approprlate alteratlons ln the slze or shape Or the chamber.
;~
.'~ ! 1, ' , , -~ 1131~33Z
Regardless o~ the size Or the test elements, rOr pr~per alignment Or the vlewlng area o~ the element wlth the ~ad~ometer 110, at locatlon 58 of the incubator, the outslde dimenslons of the test element prefer~bly are malntalned with 5 close tolerances, l.e., no greater than ~ 0.25 mm. Alter-natively, one of slde walls 52 o~ lncubator 50, and prer-erably the slde wall 52'~, Flg. 4, ls used as a rererence surface agalnst whlch the test elements are blased when they reach end portlon 58 Or the lncubator. To 80 blas the test 10 elements, prererably the top surrace 139, Fig. 7, o~ eJector element 132 is provlded wlth a rrlctlon material, not shown, that engages the ne~t test element to be vlewed as the e~ector element ls belng wlthdrawn rrom the lncubator prlor ~ the next readlng by the radlometer. The rrlctlon mate-15 rlal serves to pull the test element up agalnst wall 52'.Small pads or urethane are representatlve Or userul rrlctlon materlals.
If such rrlctlon materlal ls used, the e~ector element ls preferably rully extended lnto the lncubator when 20 the rlrst test element E is lnserted lnto the lncubator.
The test element E also ls prererably blased by a movable flnger, not shown, in the orthogonal dlrectlon agalnst one Or the walls 52, Flg. 3, that ls perpendlcular to wall 52', not shown. Such rlnger is llnked to the movement Or eJector 25 element 132 so as to clear chamber 54 when the unloadlng means ls actlvated.
The operatlon Or the analyzer wlll be readlly apparent rrom *he precedlng discusslon. A test element E ls deposited on platrorm 32 where lt 15 preheated and spotted 3 wlth a drop Or llquld by the meterlng statlon 40. Any slze drop ls userul, although lt has been round that ror test elements E descrlbed, 10 ~1 ls a prererred volume. Follow-ing the meterlng operatlon, the operator pushes handle 36 towards incubator 5Q, causlng pusher rlnger 34 to move 35 element E towards chamber 54. At the same time, cammlng bar 86 causes llnk Bo to move rod 66 upwardly, clearing cover 62 rrom chamber 54. Element E ls thus placed lnto the chamber, and the return or handle 36 to its lnitlal posltlon causes bar B6 to clear llnk 80 and thus cover 62 ralls onto ;
, . ~ . . . .....
. , :' ~ -113~32 element E at locatlon 5~ Or chamber 54. A perlo~ Or ln-cubation follows, durlng which the color density or other response, e.g., fluorimetrlc response, develops. Durlng thls tlme, addltional élements E can be spotted wlth llquld and sequentlally placed lnto chamber 54 ln like manner. Any gas that mlght otherwise evolve ~rom portlon 14 Or element E
is trapped and conflned by the coverlng relatlonshlp o~ the test element above lt, or by cover 62 lr the element ls last element E'. The resultlng pressure tends to retaln the gas wlthln the test element~ Eventually, and ln the same se-quence ln whlch the test elements are spotted, they are read by radlometer 110 and the slgnals are converted to a oon-centratlon read-out ror recordlng by the operator. Arter detectlon by the radlometer, the elements are eJected or removed by eJector element 132. Each tlme e~e¢tor element 132 ls activated to remove a test element, coatlng 142 and then coatlng 144, lf present, are read by the radlometer to malntaln proper callbratlon of the analyzer.
Optlonally, lncubator 50 lncludes temperature control means for malntalnlng walls 52 at a constant, prede-termlned, elevated temperature, ror example, 37C. A varlety of conventlonal heatlng technlques are useful. For e~ample, electrlcal elements 169, Flg. 3, are mountable wlthln or ln contact with walls 52~ In such an embodlment, cover 62 ls preferably a conductlve metal so as to be passlvely heated by walls 52 or actlvely heated by electrlcal elements mount-~- ed thereln. Such temperature control means are prererred when the detected analyte 18 markedly v~arlable with temper-ature, ror e~ample, when the analyte i8 an enzyme.
;v An addltlonal optlonal ~eature 18 a nozzle 170, Flg. 3, mounted at locatlon 58 ror dlrectlng an alr stream ~ in the dlrectlon Or arrows 172 along the readlng race o~ the ;; bottommost test element E. Such a stream removes any molsture that mlght condense on the readlng race as a result Or evolved water vapor. Nozzle 170 ls supplled, e.g., wlth alr vla a passageway 174 fed ~rom the heated portlons or wall 52. A transparent plate 178 ls disposed ~ar enough away ~rom the support surraces Or elements E 80 that a ,: . .. .
~ : . . . . - ~ -, ~.~' ' ~13193Z
Coanda alr ~low e~fect ls created as the alr stream attaches to the test element E being vlewed.
In Flg. 10, the incu~ator ls deplcted alterna-tlvely as comprislng a chamber ortented horlzontally rather than vertlcally as in the previous embodiment. Parts slml-lar to those prevlously described bear the same rererence numeral to whlch a distlngulshlng surrlx "a~ ls attached.
Thus, the analyzer comprises an lncubator 50a havlng an elongated chamber 54a wlth a longltudinal axls 60a, and a radiometer as before. Test element6 E are each lnserted lnto chamber 54a ln contact wlth the next adJacent element wlth frame members 15a extendlng generally transverse to axls 60a, also as before. However, the elements E are now lnserted through a vertlcal aperture 55a, Qhown ln dashed l~nes, and are malntalned generally vertlcally as they move from locatlon 56a to locatlon 58a. The means urglng the elements to move ln thls fashlon is a cover 62a on a rod 66a blased by a sprlng 210 to move the cover towards locatlon 58a. Rod 66a ls caused to reclprocate ln cooperatlon wlth the loading means by the ~ame mechanlsm as ls descrlbed ~or the previous embodiment, except that end 84 of llnk 80 ls posltively Journalled to end 8B Or bar 86. E~ectlon of read elements occurs as before.
The parts Or the lncubator and other de6crlbed components are metalllc or plastlc as determlned by con-ventlonal deslgn conslderatlons. If walls 52 and portlon 212 of locatlon 58, Flg. 3, are to be heated, then pref-erably they are metalllc, such as copper, whereas the portlons derlnlng passageways 113 and 121 are pro~erably plagtlc to prevent heat 1088.
In yet another embodlment, not shown, the radlo-meter ls dlsposed outside Or the lncubator, to detect from below support surface 133, t~e response of each Bllde separately after lt ls eJecte~` from the lncubator. Such an ; 35 arrangement of the detectlng means ls partlcularly preferred for test elements that are BO transparent as to ~llow the adJacent elements to be sensed lf the radiometer ls located .
- . .. . .
.- , ~31932 at the bottom of the lncubator as prevlously descrlbed.
In such an embodlment, a backing surface ls dl~posed above the support surfsce, and preferably includes a whlte reference coating that ls scanned when a test element 16 not present. me radlometer dlsposed out61de of the incubator chamber dlrects a llght beam up to the readable support portion of the element, at wlndow 18 as the element ls e~ected along path 134.
The advantages of the analyzer of the lnventlon wlll be readlly apparent from the precedlng discu6610n.
Tlme-independent access of test elements 18 po661ble wlth a rapld through-put rate. No motor, gear6, controls or rotation-permlttlng heatlng control6 are necessary for the lncubator ltself, because the lncubator 18 statlonary rather l~ than rotatlng. No addresslng or computer tracklng of addresses 18 necessary for proper retrleval of the elements ln the lncubator other than the conventlonal lndexlng devlce descrlbed above. Because no ~pace 18 requlred between test elements, the slze of the lncubator 18 reduced to a mlnlmum.
Flnally, control of evolved gases ls provlded by the arrange-ment of the test elements themselves, ellminatlng the need for speclal parts ln the lncubator chamber. The result 16 an analyzer that ls partlcularly useful at, e.g., a doctor's offlce.
2~ The lnventlon has been descrlbed ln de~all wlthpartlcular reference to certaln preferred embod;ments thereof, but lt wlll be understood that variatlons and modlflcatlon6 csn be efrected ~lthln the ~plrlt and ~cope of the lnventlon.
.~
' . . . ... . .
.: :
.
.
Claims (17)
1. In apparatus for the analysis of sample analytes using generally flat test elements having a first major surface that includes a sample-containing portion, and an opposing support surface, said apparatus including i) an incubator capable of containing a plurality of said test elements, ii) means for loading said test elements into said incubator at a first location, and means for unloading said test elements from said incubator at a second location, and iii) means adjacent said second location for detecting a response in the incubated test elements;
the improvement wherein said incubator includes means for a) defining a path between said first and second locations, and b) supporting a plurality of such elements for movement along said path with each element in contact with the adjacent elements and with the sample-containing portion of all but one of said elements being covered by said one or more support surfaces of an adjacent element.
the improvement wherein said incubator includes means for a) defining a path between said first and second locations, and b) supporting a plurality of such elements for movement along said path with each element in contact with the adjacent elements and with the sample-containing portion of all but one of said elements being covered by said one or more support surfaces of an adjacent element.
2. Apparatus as defined in claim 1, wherein said defining and said support means comprises walls providing a chamber having a longitudinal axis disposed generally perpen-dicularly to the plane of the test elements in said chamber.
3. Apparatus as defined in claim 2, wherein said chamber contains said elements in a generally vertical stack.
4. Apparatus as defined in claim 2, wherein said unloading means includes an aperture in said walls at said second location sized to permit ejection or an element from said chamber, and an ejector element adapted to reciprocate into and out of said chamber to push a test element out through said aperture.
5. Apparatus as defined in claim 4, wherein said element includes as a surface racing said detecting means, a calibrating surface.
6. In apparatus for the analysis of sample analytes using generally flat test elements having a first major surface that includes a sample-containing portion, and an opposing support surface, said apparatus including 1) an incubator capable of containing a plurality of said test elements, ii) means for loading said test elements into said incubator at a first location, and means for unloading said test elements from said incubator at a second location, and iii) means adjacent said second location for de-tecting a response in the incubated test elements;
the improvement wherein said incubator comprises wall means for defining a stationary, generally elongated chamber and, at said first location, an access aperture permitting introduction of elements into said chamber, said chamber being adapted to support a plurality or said test elements in a configuration wherein each element is in con-tact with adjacent test elements and the sample-containing portion of all but one of said elements is covered by said one or more support surfaces of an adjacent element.
the improvement wherein said incubator comprises wall means for defining a stationary, generally elongated chamber and, at said first location, an access aperture permitting introduction of elements into said chamber, said chamber being adapted to support a plurality or said test elements in a configuration wherein each element is in con-tact with adjacent test elements and the sample-containing portion of all but one of said elements is covered by said one or more support surfaces of an adjacent element.
7. In apparatus for the analysis of sample analytes using generally flat test elements having a first major surface that includes a sample-containing portion, and an opposing support surface, said apparatus including i) an incubator capable of containing a plurality of said test elements, ii) means for loading said test elements into, and means for unloading said test elements from, said incubator, and iii) means for detecting a response in the incubated test elements;
the improvement wherein said incubator comprises wall means adapted to receive and maintain a plurality of said elements in a contiguous stack, with said sample-containing portion of all but one of said elements being covered by said one or more support surfaces or an adjacent element in the stack;
said detecting means and said loading means being disposed with said stack generally between them and said detecting means being positioned to detect the bottommost element of said stack, said unloading means being disposed adjacent said detecting means.
the improvement wherein said incubator comprises wall means adapted to receive and maintain a plurality of said elements in a contiguous stack, with said sample-containing portion of all but one of said elements being covered by said one or more support surfaces or an adjacent element in the stack;
said detecting means and said loading means being disposed with said stack generally between them and said detecting means being positioned to detect the bottommost element of said stack, said unloading means being disposed adjacent said detecting means.
8. In apparatus for the analysis of sample analytes using generally flat test elements having a first major surface that includes a sample-containing portion, and an opposing non-sample-containing surface, said apparatus including i) an incubator capable of containing a plurality of said test elements, ii) means for loading said test elements into said incubator at a first location, and means for unloading said test elements from said incubator at a second location, and iii) means for detecting a response in the incubator test elements;
the improvement wherein said incubator includes guide means for guiding a plurality of such test elements in succession from said first location to said second location with each element being in contact with adjacent elements;
said loading means being disposed to orient ele-ments in said guide means such that the sample-containing portion of all but one element is covered by said non-sample-containing surfaces of an adjacent element.
the improvement wherein said incubator includes guide means for guiding a plurality of such test elements in succession from said first location to said second location with each element being in contact with adjacent elements;
said loading means being disposed to orient ele-ments in said guide means such that the sample-containing portion of all but one element is covered by said non-sample-containing surfaces of an adjacent element.
9. Apparatus as defined in claim 8, and further including means for urging elements in said guide means into such contacting relation.
10. Apparatus as defined in claim 9, wherein said urging means includes a spring under compression.
11. Apparatus as defined in claim 1 further including means for covering said one element not covered by an adjacent element.
12. Apparatus as defined in claim 11, wherein said covering means includes a movable cover, i and further including means operatively connecting said cover to said loading means to displace said cover away from said detecting means while additional elements are being loaded.
13. Apparatus as defined in claim 1, 6, or 7, and further including means for urging the test elements through said incubator towards said detecting means.
14. Apparatus as defined in claim 1, 6, or 8, and further including means for maintaining said incubator at a predetermined temperature.
15. Apparatus as defined in claim 1 or 6, and further including means at said second location for di-recting an air stream across said support surface of each of said elements so that condensed moisture is removed prior to reading.
16. An incubator for an analyzer that detects sample analyte responses in generally flat test elements having a first major surface that includes a sample-con-taining portion, and an opposing support surface, the incubator comprising wall means structured to receive said test ele-ments one at a time at a first location, said wall means a) defining a path from said first location to a second loca-tion suitable for the detection of the responses, and b) being configured to support the test elements along said path each in contact with the adjacent elements, the sample-containing portion of all but one element being covered by said support surfaces of an adjacent element, and means for maintaining said incubator at a pre-determined temperature.
17. A method of detecting analytes of sample liquids by the generation of detectable responses in test elements each of which contains a quantity or one of said liquids in a sample-containing portion; the method comprising the steps of a) sequentially placing the elements in a con-figuration wherein each element is in contact with the adjacent elements and the sample-containing portion of all but one of said elements is covered by a support surface of one of said adjacent elements, b) detecting said responses of said elements in the same sequence as they are placed in said configuration;
and c) removing said test elements from said configuration either before or after said detecting step.
and c) removing said test elements from said configuration either before or after said detecting step.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/177,050 US4303611A (en) | 1980-08-11 | 1980-08-11 | Analyzer apparatus featuring a simplified incubator |
| US177,050 | 1988-04-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1131932A true CA1131932A (en) | 1982-09-21 |
Family
ID=22646978
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA364,404A Expired CA1131932A (en) | 1980-08-11 | 1980-11-10 | Analyzer apparatus featuring a simplified incubator |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4303611A (en) |
| EP (1) | EP0046087B1 (en) |
| JP (1) | JPS57115199A (en) |
| CA (1) | CA1131932A (en) |
| DE (1) | DE3174246D1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4647431A (en) * | 1980-05-31 | 1987-03-03 | Fuji Photo Film Co., Ltd. | Device for maintaining a constant temperature for chemical analysis |
| US4430299A (en) * | 1981-06-18 | 1984-02-07 | Coulter Electronics, Inc. | Apparatus for monitoring chemical reactions |
| JPS5821566A (en) * | 1981-07-31 | 1983-02-08 | Fuji Photo Film Co Ltd | Incubator |
| US4424191A (en) * | 1982-03-04 | 1984-01-03 | Eastman Kodak Company | Analyzer featuring loading and unloading means for a storage chamber, and common drive means |
| US4512952A (en) * | 1982-07-01 | 1985-04-23 | Eastman Kodak Company | Apparatus for storing and dispensing analysis slides |
| US4487839A (en) * | 1983-01-05 | 1984-12-11 | Ortho Diagnostic Systems Inc. | Immunoassay methods employing patterns for the detection of soluble and cell surface antigens |
| DE3321783A1 (en) * | 1983-06-16 | 1984-12-20 | Boehringer Mannheim Gmbh, 6800 Mannheim | ARRANGEMENT FOR EVALUATING A TEST STRIP |
| US4566798A (en) * | 1983-11-10 | 1986-01-28 | Eastman Kodak Company | Method for calibrating a reflectometer containing black and white references displaced from the sample position |
| JPS61198041A (en) * | 1985-02-28 | 1986-09-02 | Konishiroku Photo Ind Co Ltd | Biochemical-analyzing instrument |
| US4798705A (en) * | 1985-12-24 | 1989-01-17 | Eastman Kodak Company | Compact analyzer |
| DE3786087T2 (en) * | 1986-02-07 | 1993-09-16 | Fuji Photo Film Co Ltd | DEVICE FOR CHEMICAL ANALYSIS. |
| US4814279A (en) * | 1986-03-17 | 1989-03-21 | Fuji Photo Film Co., Ltd. | Incubator for chemical-analytical slide |
| JPH0442777Y2 (en) * | 1986-09-03 | 1992-10-09 | ||
| US4933291A (en) * | 1986-12-22 | 1990-06-12 | Eastman Kodak Company | Centrifugable pipette tip and pipette therefor |
| GB8704267D0 (en) * | 1987-02-24 | 1987-04-01 | Fisons Plc | Device |
| JPH087221B2 (en) * | 1987-07-03 | 1996-01-29 | 富士写真フイルム株式会社 | Chemical analyzer |
| US5169600A (en) * | 1987-07-15 | 1992-12-08 | Fuji Photo Film Co., Ltd. | Biochemical analysis apparatus for incubating and analyzing test sites on a long tape test film |
| US4857471A (en) * | 1987-07-20 | 1989-08-15 | Eastman Kodak Company | Analyzer with wash station separate from incubator |
| JPH0731120B2 (en) * | 1988-10-20 | 1995-04-10 | 富士写真フイルム株式会社 | Incubation method |
| US5059393A (en) * | 1989-01-05 | 1991-10-22 | Eastman Kodak Company | Analysis slide positioning apparatus and method for a chemical analyzer |
| CA2015910C (en) * | 1989-05-09 | 1995-01-03 | James David Shaw | Flexible pusher blade and housing |
| US5089229A (en) * | 1989-11-22 | 1992-02-18 | Vettest S.A. | Chemical analyzer |
| US5250262A (en) * | 1989-11-22 | 1993-10-05 | Vettest S.A. | Chemical analyzer |
| US5207987A (en) * | 1990-05-21 | 1993-05-04 | Pb Diagnostic Systems Inc. | Temperature controlled chamber for diagnostic analyzer |
| US5576215A (en) * | 1991-06-03 | 1996-11-19 | Abbott Laboratories | Adaptive scheduling system and method for operating a biological sample analyzer with variable interval periods |
| US5289385A (en) * | 1991-06-03 | 1994-02-22 | Abbott Laboratories | Adaptive scheduling system and method for operating a biological sample analyzer with variable rinsing |
| EP0523426B1 (en) * | 1991-07-16 | 1996-03-06 | Johnson & Johnson Clinical Diagnostics, Inc. | Device for feeding objects into a waste bin of an analyzer |
| JPH0783834A (en) * | 1993-09-14 | 1995-03-31 | Fuji Photo Film Co Ltd | Method of biochemical analysis |
| US5599501A (en) * | 1994-11-10 | 1997-02-04 | Ciba Corning Diagnostics Corp. | Incubation chamber |
| US5665312A (en) * | 1995-11-14 | 1997-09-09 | Coulter International Corp. | Blood analysis system having blood storage, transport and automatic slide-making capabilities |
| US7396508B1 (en) * | 2000-07-12 | 2008-07-08 | Ventana Medical Systems, Inc. | Automated molecular pathology apparatus having independent slide heaters |
| US6331437B1 (en) | 1998-07-14 | 2001-12-18 | Bayer Corporation | Automatic handler for feeding containers into and out of an analytical instrument |
| US7273591B2 (en) | 2003-08-12 | 2007-09-25 | Idexx Laboratories, Inc. | Slide cartridge and reagent test slides for use with a chemical analyzer, and chemical analyzer for same |
| US7588733B2 (en) | 2003-12-04 | 2009-09-15 | Idexx Laboratories, Inc. | Retaining clip for reagent test slides |
| US9116129B2 (en) | 2007-05-08 | 2015-08-25 | Idexx Laboratories, Inc. | Chemical analyzer |
| US9797916B2 (en) | 2014-01-10 | 2017-10-24 | Idexx Laboratories, Inc. | Chemical analyzer |
| EP3644064B1 (en) * | 2018-10-23 | 2021-08-18 | Roche Diagnostics GmbH | Method of handling laboratory sample containers and apparatus for handling laboratory sample containers |
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|---|---|---|---|---|
| US3260413A (en) * | 1964-08-31 | 1966-07-12 | Scientific Industries | Automatic chemical analyzer |
| GB1198488A (en) * | 1966-08-23 | 1970-07-15 | Hans Peter Olof Unger | Improvements in or relating to Automated Analysis |
| US3728227A (en) * | 1968-06-18 | 1973-04-17 | North American Rockwell | Microorganism culture apparatus |
| US3562114A (en) * | 1970-01-05 | 1971-02-09 | Richard M Steidl | Apparatus for incubation cultures |
| US4047032A (en) * | 1975-06-09 | 1977-09-06 | Technicon Instruments Corporation | Standard for spectral reflectance |
| CA1054034A (en) * | 1975-06-20 | 1979-05-08 | Barbara J. Bruschi | Multilayer analytical element |
| US4029419A (en) * | 1975-10-10 | 1977-06-14 | International Business Machines Corporation | Textile color analyzer calibration |
| US4118280A (en) * | 1976-05-03 | 1978-10-03 | Mcdonnell Douglas Corporation | Automated microbial analyzer |
| LU77642A1 (en) * | 1976-07-09 | 1977-10-03 | ||
| FR2357881A1 (en) * | 1976-07-09 | 1978-02-03 | Dev Automat Biolog | Testing liq. microsamples esp. blood with various reagents - with multiple reagent syringes operating simultaneously to load and discharge |
| US4056358A (en) * | 1976-11-22 | 1977-11-01 | Baxter Travenol Laboratories, Inc. | Apparatus for deriving blood oxygen association curve information |
| US4152390A (en) * | 1976-12-17 | 1979-05-01 | Eastman Kodak Company | Chemical analyzer |
| US4224032A (en) * | 1976-12-17 | 1980-09-23 | Eastman Kodak Company | Method and apparatus for chemical analysis |
| CA1099951A (en) * | 1976-12-17 | 1981-04-28 | Clyde P. Glover | Automatic chemical analysis of biological fluids |
| US4151931A (en) * | 1978-06-05 | 1979-05-01 | Eastman Kodak Company | Article dispenser apparatus for use in an automated chemical analyzer |
-
1980
- 1980-08-11 US US06/177,050 patent/US4303611A/en not_active Expired - Lifetime
- 1980-11-10 CA CA364,404A patent/CA1131932A/en not_active Expired
-
1981
- 1981-08-11 DE DE8181303658T patent/DE3174246D1/en not_active Expired
- 1981-08-11 JP JP56125833A patent/JPS57115199A/en active Granted
- 1981-08-11 EP EP81303658A patent/EP0046087B1/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| EP0046087B1 (en) | 1986-04-02 |
| DE3174246D1 (en) | 1986-05-07 |
| JPS57115199A (en) | 1982-07-17 |
| EP0046087A3 (en) | 1982-05-05 |
| EP0046087A2 (en) | 1982-02-17 |
| JPH0239745B2 (en) | 1990-09-06 |
| US4303611A (en) | 1981-12-01 |
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