CA2146684A1 - Photometric device - Google Patents

Photometric device

Info

Publication number
CA2146684A1
CA2146684A1 CA002146684A CA2146684A CA2146684A1 CA 2146684 A1 CA2146684 A1 CA 2146684A1 CA 002146684 A CA002146684 A CA 002146684A CA 2146684 A CA2146684 A CA 2146684A CA 2146684 A1 CA2146684 A1 CA 2146684A1
Authority
CA
Canada
Prior art keywords
light
assay plate
series
photometric device
test light
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.)
Abandoned
Application number
CA002146684A
Other languages
French (fr)
Inventor
Mark Wechsler
Howard H. Barney
Roger A. Kaye
David G. Ogle
Michael M. Lacy
Calvin Y. Chow
Kimberly L. Crawford
Dean G. Hafeman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Molecular Devices LLC
Original Assignee
Mark Wechsler
Howard H. Barney
Roger A. Kaye
David G. Ogle
Michael M. Lacy
Calvin Y. Chow
Kimberly L. Crawford
Dean G. Hafeman
Molecular Devices Corporation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Mark Wechsler, Howard H. Barney, Roger A. Kaye, David G. Ogle, Michael M. Lacy, Calvin Y. Chow, Kimberly L. Crawford, Dean G. Hafeman, Molecular Devices Corporation filed Critical Mark Wechsler
Publication of CA2146684A1 publication Critical patent/CA2146684A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/33Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/251Colorimeters; Construction thereof
    • G01N21/253Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/02Mechanical
    • G01N2201/023Controlling conditions in casing
    • G01N2201/0231Thermostating
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/04Batch operation; multisample devices
    • G01N2201/0446Multicell plate, sequential
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/12Circuits of general importance; Signal processing
    • G01N2201/122Kinetic analysis; determining reaction rate
    • G01N2201/1222Endpoint determination; reaction time determination
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00Features of devices classified in G01N21/00
    • G01N2201/12Circuits of general importance; Signal processing
    • G01N2201/127Calibration; base line adjustment; drift compensation
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates

Abstract

The present invention relates to a photometric device for measuring optical parameters. The invention functions in the ultraviolet light range through use of a monochromator and splits the test light in multiple channels by a rotor assembly, including a mirror.

Description

21~668~ ' ~CXGROUND OF T~ v~ ON
A varl-ty of t-~n~ques and devic-J ar~ commercially available for th- d-t-etion and ~-a-ur-~ent of ~ub-t~n~ nt in fluid or oth-r tran-lue-nt ~a~pl-- by d-ter~ining th- light tran~ ivity of th- ~a~pl- ThQ~ can b- broadly cat~goriz-d into d-vic~- which m-a~ur- th- optical prop-rti-s of on- ~a~pl- or a ~~all number of sa~ple~ ntially ~i~ult~ ~ol~ly and tho~- whieh ~a-ur~ a larg~
nu~b r of ~a~pl-~ -ntially ~i~ultan-ou~ly Photou-trie d-vice~ that simultan~ouJly p-rfor~ individual a--ay- on a plurality of liquid or oth-r tran-lue-nt ~a~pl-- u~ a ~ulti-a~ay plat- which eontains an array of ve~ , sueh a- ~ight row~ by tw-lv- columna (8x12), four rows by ~ix eolu~n~ (4x6), two rowa by t~r-- eolu~n- (2x3), fiv- rowa by ~ight eolu~na (5x8) Typieally, th- v ~ of th~ ~ulti-as-ay plat- aro ~pae-d at nin-(9) ~illiu-t~r c~nt-r~, hav~ a volume of approximat-ly four hu dL-d (400) uillilit-r~, and hav- a h~ight of approxi~at-ly on~ (1) e-ntiu t-r Th- ~ulti-a-say plat~ ad- of mat~rial, sueh a~
poly~tyr-n- or poly-thyl-n-, that i~ optieally tran-par~nt at th-wav-l-ngth- of int-ra~t Th- optieal d-naity of th- ~ampl-~ ia ~ a~ur~d by d-t-r~inlng th- a ount of light att-nuation Llght pa~-ing t~ough th~
tran~lue nt ~a~pl-~, eontain d in th- ~ulti-a~-ay plat- v~ ls, is co~par d to ~ r-f-r-ne- by ~ ntional photodat-etor-A wid-~pr-ad u~- of ~ulti-a~ay plat-a i~ in th- ~nzy~--link~d i~ouno~orb nt a--ay (ELISA) t~chniqu- whieh i~ u~-d ~or d~teetion and guantitation of an ~xt-n~iv rang- of ~ub-tane-- and biological 8'~-cell- in academic ~ rch ~nd biot~ ology ~ well as for ~ clinieal t--ting In ~uch a--ay~, ~ol-cùl-~ of a ~ark-r ~nzy~
(~ueh a- al~alin- pho~phataB-) ar~ d-po~it-d on th- botton and part way up th- ~id-- of ~ach o~ th- v~---l- of a nulti-a~say plat~;
~ach v-~--l having b--n a~sign~d to int-ract pr-viou-ly, dir~ctly or indir-ctly, with a ~a~pl- cont~n~n~ an analyt- of int-r~t Th- nu~b r of narker enzym~ molecul~- bound to ~aeh vQ~el Or thQ
plat- i~ a funetion of th- CG. _ ~ ntration of analyt- in th- ~ampl-of int-r-~t D-t~r~ination Or the activity of th- bound Qnzyme, th-r-for-, p ruits d-t-ction or quantitation of th- analyt-For d-t-rnination of fluid-pha-- ~nzy~ aetivity, ~ t t~ ~n~u-- for both ~ rch and clinical application- ~-ploy kin-tie analyai- which involv-- m-a~ur-ment of th- initial rat- of ~nzyu -eatalyz d, chronog~nie r~aetion~ in th- pr~--ne- of ~
of th- ~nzyn ~ub~trat~; a ~fC_ a~l~r- whieh ha~ ~-v-ral w-ll known advantag-- ov-r th- alt-rnativ- ~-nd-point~ analy-i- a-thod o~
allowing th- ~nzyn- to r-aet with a ehrouog-nie ~ub~trat- for a ~ix d p riod of ti~ and th~n making a ~ingl- optical d-n~ity n-a-ur-~ nt aft-r ~ne~nq th- ~nzy~ ~ In kin-tie analy~
multipl- r-ading- ar- nad~ within th- int-rval (typieally lin-ar) r-aetion poriod and th- int-rval- b tw-~n r-ading- ar- n-e-~-arily ~hort (typie~lly l-~- than 30 ~ d~) By u~ing kin-tie analy~is, th- i ~duetion of ~rror~ eau--d by (a) di~f-r-ne-~ in initial optieal d-n~ity and/or (b) lo~- o~ ind~p nd-ne- fro~ ~ub~trate co _~ntration, i- ~ub~tantially avoid-d Exa~pl-~ inelud- th- u~-of NADH and NADPH, a~ d--erib d, ~or ~xaapl-, in ~-~n~ng-r, -- 214~84 ~Bloch~ try, the Molocular Basi~ of Cell Structur- and Function,~

Worth Publi-h-r- Inc , New York, 1970 Photou-t-r~
capabl- Or ~-a-uring th~ ab~orbance of ultravlol-t light by NADH or NADPH at about 340 nanom-t-r~ wav~length ar- partlcularly usQ~ul ~n per~oruing ~uch aa-ay~
Curr-ntly availabl~ automat-d optical d-n~ity u-a-urem-nt in-truu nt- ~or uulti-a~ay plate- r-gulat- th- t-~p ratur- of th-plat- with radiant h-ating, i e , hoating a ~-tal ~urrac- and lo radiating thi~ h-at onto the multi-assay plat- Alternativ-ly, th-uulti-a~ay plate~ ar- h-ated by air conv-ction, i e , h-ating air and rorcing it past th~ plate A limitation or th- ~xistlng air conv-ction h-ating t~chnology is that th- plat- tak-- a long ti~-to war~ up and r-ach equilibriu~, adding to th- ti~- roquir-d to tak- u-a-ureuent~ Anoth-r limitation o~ exi~ting t~hnology i8 that th- out-r v-~--l-, having more ~Yr~ ~urrac- area, war~ up ~or- quickly than th- inner ves~ and r-ach a dirr~rent equilibriuu te~p~rature Tb- reaction rat- and th- rat- Or change ot optlcal ~b-orption ~or ~om- sp-cin-n- ~F- ~ upon th~
t-up r~tur- Or th- ~p-cim-n In a kin-tlc t--t Or ~ueh ~p-ciu-n-, a t--p-ratur- dlrr-r-ne- betw~-n v-~--l- lead- to an ~rron-ou-re~ult Anoth-r liuit~tion Or exi~ting teehnology i~ th~t ~oi~ture can cond-n-- on th- optleal eompon~nts eau~lng lo-~ Or rocu- and att-nuation du- to scattering Or th- light ~ignal Solv~nts eont~in-d ln th- moi~tur- e~n eaus- eorro~ion on tho sur~ae~ o~
th- optieal, m-chanleal, and electric~l eompon-nt- l~adlng to 21 ~66~
furth~r att-nu~tion of the light signal and ~ventually to failure ~ of th- in~trum nt Exi-ting photo~ tric device~ capabl- of m-a-uring multi-a~-ay plat-- hav- b -n limited in th- rang- and s-l-ctivity of th- light ~ tl~ that i~ provided for m-a~ur~ment and analy~i~ Thi~
limitation ari~- becau~- th~ light ~ourc- n--d- to b di~tributed to a plurality o~ samplQ~, typically r-quiring multipl~
di~tribution ~l-m~nt~ and a v-rtical illumination of th- ~mpl-~
Prot-in- and D-oxyribon~cl-ic Acid~ (DNA~) a- w-ll a- many lo chromog-nic ~ub-trat-~ ab~orb at wav-l-ngth- ~hort~r than 340 nano~ct-r~ . Currently availabl- photom-tric in~-~um-nt~ that can op rat- at wav-l-ngth~ le~ than approximat-ly 340 nanom-t~rs ar~
limit d to a~ay- on on- or a ~mall numb~r~ of sample~, th-r~by making larg- ~cal- kin-tic analy~i~ assay application~ impractical du- to th- ~xt~n~ sampling timc~ Additionally, currently availabl- photom tric ~ n ~tl ~ment~ ar- limit~d to analy~i~ at a ~ingl~ or ~~all nu~b~r of excitation wav-length~, th-roby naking ov-rall ~ull ~p-ctrum analy-is impractical Anoth-r limitation a--ociat~d with conv-ntional photom-tric d-vic~-, wh~n u~-d for assaying chromog~nic roaction- kin-tically, i~ that th- ~on~ntional d-vica~ ar- ~ub~-ct to ~rror~ ari-ing from ~rratic r di-tribution of th- colored product a~ a r-~ult of phaso ~-paration and/or uncontroll-d bulk mov~m-nt of th- aqu-ou~ pha~-of th- ~a~pl- during kin~tic analy~i~ Moro ~p~cifically, in th~
cas- of ELISA protocol~, wh~re th~ ~nzy~c i~ bound to th~ pla~tic ~urfac- of tho multi-a~ay plato ves~ls (on tha botto~ and part 21~6~8~
way up th- ~id-s), th~ bound enzyme interacts with an unatirred aqu-ou~ pha-- lay-r which causes loealiz-d phas~ ~eparation of the color d produet of th- ~nzy~e reaetion du- to it- high loeal cone-ntratiOn Thi- s-paration i L~ f~ an unguantifiabl- ~rror s and a d-gr-- of non-linearity into ~ueh kin-tie m-asur~ment~ Even in ea--- wh-re th~ eolored produet r-~ain~ in tru- solution, ~rratie bulk aov~ent of th- aqu-oua pha-- l-ad~ to uneven r-di~tribution of th- cG ~ntrat-d produet and h-ne- to an unquantif$abl- error Convantional multi-assay plato photometrie measuring in-tru~ nt- ar- further limited in th-ir utility by th-ir u~- of interf-r-ne- filt-r~ in seleeting a pr-ei~- wav-length of t-~t light Fix d int-rfer-nee filter~ ar- eon~trueted to provid- a ~ingl- ~ -r~in-d t-st wav-length that eannot b ~a-ily ehang-d Th- u~-r nu-t ehang~ filter~ to ehange te~t wav-length~ Ev-n with a filt-r whe-l, m-asurem-nt~ at mor- than a f-w wav-l-ngth- and ~p-etrun ~ a~ure~entJ ar- impraetical Continuou-ly variable int-rf-r-ne- filt-r- are diffieult to manufaetur- in a pr-ei~-ly reprodueibl- way and photo~-tric in-trument- with ~uch fllter- are diffieult to calibrat- B-low 340 nano~eters variabl- filt-r- are diffieult to anufaeture ~o a- to have ad-quat- ultraviolet light tranJ~ ion.
2~4~6~
SU~ Y OF T~ P~C~T l~r~.lON
In a flr-t principal a-p~ct, th- yl~ent inv-ntion i~ a photon-triC d-vic- for u-a~uring th- optical prop-rti-- of ~ample~
in nulti-a--ay plat-~ An excitation light ~ourc- and a s ~onochro~ator provid- e-s~ntially monochrouatic t--t light which i-di~tribut-d ~ qu-ntially through a di-tribution n-twork of optical fiber- to illu~inate and test the sample- A plat- carrier move~
th- nulti-a--ay plat- ~o that each coluun of ~ i- po-itioned, in turn, at a n a-ur-~ent ~tation for illu~ination and t--ting 10 Photodet-ctor- CG~ rt the test light pa-~-d by the sa~pl-- into r-p~ ativ ~l-etrical output ~ignal-In a ~ -n~ principal a~pect, the ~ nt inv-ntion relates to an i~o~.d te-t light gen-rating ~y~t-m for us- in a photometrie d-vic- Th- g-n-rating sy~t-m include- a flash laup to provid- a 15~eri-~ of light fla-he- having a fir-t wavel-ngth rang- A
onochronator r-~pon-iv ly produc-- ~---ntially uonochromatic te-t light having a ~-cond wav-l-ngth rang- within th- fir~t Th-~y-t- i- eapabl- of g-n-rating ultraviol-t t--t light having a wav-l-ngth a~ low a- 200 nano~ t-rs and a~ high a- 1~00 nanon-t-rs 20In a third prineipal a-p et, th- pre~ent invention r-lateJ to a b a~ ~plitt-r for ~plitting a ref_l~r-~ froD th- te-t light Thi~ ~plit r-f-r ne- ~ub-tantially avoid~ inaccuraci-a du- to the inher-nt a~plitud- fluetuation- in te~t light euitt-d by a fla~h lanp 25In a fourth prineipal asp-et, the pr---nt inv-ntion r-lat-- to a n-ehani~n for alt-ring th- dir-ction of wav-l-ngtha of ultraviol-t light as low as 250 nanometer~ without substantial lo~
of int-n-ity A~ nown in the art, ~plastic~ or ~b ndable~
optical fib-r- ab-orb ultraviolet light and thu- ar~ ~n~ ~ptable for appllcatlon- r-quiring ~uch light Gla-- fib r~, on th- oth-r s hand, ar- not ~uff$ci-ntly flexibl- for u~- in nonlin-ar path application~, particularly wh-r- th- radiu- of curvatur- is le88 than t~n (10) ti~ th~ fib~r diam-t-r Th- dir-ction alt-ring ~ h~nt-~ r-c~iv-- light ~ itt-d by an optical fib r in a fir-t dir-ction Th- ~ nt~ includs~ a rotor a~-- bly having at l-a-t one mirror op-rabl- in a ~~ri-- of mirror po~ition- Each po-ition CO~ pon~ to an altsr~d light tran-~i~-ion dir~ction Th~ rotor a~-~bly accommodat~- a nonlin-ar light path, including both fold-d and curvilinQar path-, a- i- typically i- r-quir-d by th- g-om-try of th- d-vic- Th-rotor a~-~bly ~ignificantly reduc~ th~ numk~r of compon-nts oth-rwi-- r-guir-d by changing "~ingl- ch-nn~l~ light fro~ a sourc~
into ~uultipl- chann-l~ light for tran-mi--ion to multipl- v-~
of th- uulti-a-~ay plat-In a fi Kh principal a~p-ct, r-lat-d to th- fourth a~p ct, th-~ nt inv-ntion r-lat-- to a photod-t~ctor d-vic- utilizing a fla~h la p, wh-r-in ~-ingl- chann-l~ light i~ ~plit to provid- a r~f-r-nc- prior to co v~r-ion into ~multipl- chann-l~ light The r-f-r-nc- light i- u~-d to d-t-ct th- inher-nt a~plitud- variations in th- light ~-itt d fro~ such an excitation light ~ourc-In a ~ixth principal a~p~ct, th~ pr~--nt invontion r-lat-s to a te~p ratur~ cGl~Lol m~c~An~ for u~- in con~unction with a 21~668~1 photo~ tric d~vice for measuring optical Y~ol rtie~ of samples - within v~ of a ~ulti-a~ay plat- Th- control ~e~h-nism r-gulat-- th- t-np-ratur- of th- ~ampl-- during th- optical nea~ur-u-nt ~L~_e-- and provide~ ~ub~tantially uniforo and rapid h~ating of th- ~anpl-- A ~ S~ ~ 9 ~ ~ in tho ~ulti-a--ay plat~ Th~
t~p ratur- co ~ol ~-chani~ includ-- a hou-ing, ~ub-tantially ~nclo-ing th- ~ulti-a~-ay plat- in a clo--d ~tat-, and a ~upply of h-at-d air Th- h-at-d air flow- through ap .L~k~- in a baffle, iupinging upon th- - - t~ surface~ of th- ~ulti-a--ay plat- Th-ap-~Lu~ ar- arrang~d or sized so that th- c-ntral ~ in the ~ulti-a~-ay plat- r-c-iv- a greater flow of haat-d air than th-p riph-ral v~---l- ~o a~ to achiQv- a ~ub~tant$ally unifor~ h~ating rat- and final t-~p-ratur-In an ~-v-nth principal a~p-ct, th- ~ nt inv-ntion r-lat--to a Ui~. G~ or-ba~-d photometric d-vic- Th- proc-~sor CG ~ol- th- op-ration of th- d-vice, including ~-a-ur~-nt of th-~l-ctrical ~ignal- r-~ entativ- of th- light that ha- pa~--d through th- ~a pla- and t~mpcraturc control of th~ cha~b~r ~ o~ ~ing th- uulti-a--ay plat- Pr-f-rably th- ~ or includ-- a k-y ~ntry ~y-t-~ and a di-play, ~uch that t--t- can b-initiat-d and ~ gu-ncad and t-~t r~-ult- can b- di~play-d and print d Th- typical t--t r--ult~ rapr---nt light ab-orbanc-, light ~catt~ring, fluo~ c~nc~ and/or pho-pho~c~nc~
It i- thu- an ob~-ct of th- pr~--nt inv ntion to provid- an ~cononical, roadily ~aintainablo photomotric d-~ic- It i~ al~o an ob~ct to provid- a photo~ tric dovic- op-rabl- in th- ultraviol-t 214~6~
rang~ , at a wav-length as low as 250 nanometers Another ob~-ct i- ~ ~ulti-a--ay plat- photom-tric d-vic- having simplicity in t~r~J ot ~tructur- and op-ration Still another ob~-ct i~ a photou tric d-vic- capabl- of accurat- ~a-ur-~-nt at a sp--d of s l~s- than t-n (10~ d~ p-r microplat~
Anoth-r ob~-ct is to provid- a photo~-tric sy-t-~ wh-r-in light initially iB carri~d fro~ th- ~ourc- by a ~ingl- optical fib r, ~ub-tantially r~ducing n~J--ry part- and co~pon~nt~ and sub-tantially facilitating wav-l-ngth ad~u-tm-nt and a~plitud-sa~pllng of th- light Still another ob~ect of th- y.c-~-nt inv-ntion iJ an imy.ov-~ ~-chanism for r-dir-cting light fro~ a singl- optical fib~r to a series of di~tribution optical fib r~
corr--ponding to th- v ~1- in ~ach column of a multi-as~ay plat-Y-t anoth-r ob~oct i~ a light redir-cting mech~nis~ utilizing a rotatabl~ nirror to ~ub~tantially avoid 108- in tha a~plitud~ of th- r-dir-ct-d light It i- a furth-r ob~-ct ot th- pr-~-nt inv-ntion to provid- a photon-tric d-vic-, utilizing a multi-assay plat-, wher-in fluid ~anpl- t-~p ratur- i- highly r-gulated Anoth-r ob~-ct is a t-np ratur- CG ~ol ~y-t-n ~ub-tantially r-ducing th- accu~ulation of flan abl- vapor fro~ tha fluid sampl-- (~uch a- h-xan-, i~ooctan-, and nitro~ than-) within tho hou~ing, th~reby ~ub~tantially d-cr-a~ing th- pot-ntial hazard of a fir- or an ~xplo~ion Y-t anoth-r ob~-ct of th- inVQntion i~ to sub~tantially avoid cond-n-ation within th- hou~ing ot th- photo~-tric devic-214~68~ ' Th--e and other features, objecte and advantagee of the - ~L'- ~-nt invention are set forth or implicit in the following detail-d d--cription.

21~6fi~ ' B~TFF DF~CRIPTION OF T~ DRAWING
~~ Pr-f-rred e~bodi~ents of the pre--nt invention ar~ described, in d-tail, with reference to the drawing wher-in FIGURE 1 1~ a bloc~ diagram illustrating th- ~a~or compon-nt~
of the photouQtric d-vice;
FIGURE 2 is a ~chematic of the optical syst-~ of the preferred ~mbodi~-nt of th~ nt inv-ntion ~hown in FIGURE l;
F$GURE 3a i~ a cross-~-ctional view of the photo~ tric device in a clo--d ~tat-;
FIGURE 3b i- a partial cros~-~-ctional, partial top vi-w of the eDbodia nt ~hown in FIGURE 3a;
FIGURE 4 is an ~l~ctrical schematic diagram according to a pr-~-rr-d e~bodinent of the present inv-ntion;
FIGURE S i~ a tining diagram relating to th- m-a-ur-m-nt p~ p-r~ormed by the pre~ent invention;
FIGURE 6 ia a flow chart of the power-up ~-qu-nce for a pr-f-rr-d ~ bodi~-nt of the y~3~nt inv-ntion;
FIGURE 7 i- a flow chart of th- g-n-ral ~equence of op~ration according to a pr-f-rr-d e~bodim-nt of th- invention;
FIGURE 8 i~ a flow chart of a m-a~ureo-nt s-qu-nc- for a pref-rr d ~-bediu-nt of th- pre~ent invontion utilizing a microplat-;
FIGUR~ 9 i- a flow chart of a dark current calibration sequenc- for th- pr-f-rred embodiment of th- pr--ont inv-ntion;
FIGURE ~O i~ a flow chart o~ a tran~ ion calibration sequenc-;

2146~8~
FIGURE 11 is a flow chart of an operational measurement - ~equ-ne- wlth r-sp~ct to a colu~n of a multi-a~say plate according to a pr-f-rr-d ~~bodim-nt of the p~e~ent invention;
FIGURF 12 i~ a flow chart of a ~ampl- u a~ur-m-nt s-qu-nce;
FIGURE 13 is a flow chart of an optinization ~-qu~ne- for th-el-ctrical compon-nts of ~ preferr-d embodim-nt of th- ~L~ Y~nt inv-ntion;
FICURE 14 i~ a ~eh~matic top vi-w of th- eha~ber of thQ
photom tric d~vic~ ~howing a ~ccnd h-ating ~y~teu ~mbodim~nt;
FIGURE 15 is a top view of the baffl~ o~ at-d into the heating ~y~tem embodim-nt shown in FIGURE 14; and FIGURE 16 is a front view of the filt!r wh-Ql incorporated into th- optic~ ~y~tem of the photometric dsvic- shown in FIGU~E 1 214668~
DFT~rTFn DFCC~TPTION OF P~FF~RED ~BODIMENTS
- R-f-rring to FIGURE 1, a preferr-d ~mbodi~-nt of th- present inventlon is shown as a photometr$c devic- or n-a~ur-~ent ~ystem, g~n-rally d--ignated 10, ~or testing fluid ~amples contained in ves~Qls in a nulti-assay plat- 12 Th- ~ulti-as-ay plat- 12 $~ a conv-ntional ~icroplat-, $ncluding a st~n~rd array of vess-l~
arrang-d in eight (8) row~ by tw-lv- (12) colu~n~ (8x12) The photo~-tric n-asurement syst-m 10 includ~- and op-rates, in a cG ~_ ~ional ~anner, under the d$r-ction and CO~LO1 of an acguisition and CG~ILLO1 ~Lo~e~cr means 14, a cc ~al ~o~Qas$ng unit ~-ans 15, and a u~-r $nterface co~puter 30, as further d~scrib~d h~r-in, which c._~erat~v-ly d-f~n- ~LO~ ~or ~-an- 25 ~or $nitialization, ~et-up, data acquis$t$on, analysis and d$splay a light ~ourc- ~eans 22 emit~ a band of wav-lengths of light having a first wav-length rangQ of approxi~ately 200 nano~eters to approximately 1100 nanometers A desired, essentially Donochro atic light, with a wav~l-ngth in th- rang~ of 250 to 750 nano~ t-rs, i- ~-l-ct-d by a wavel-ngth s-lection ~-ans 23 and d-liv-r-d through an optical fiber 58 to a light di-tribution means 24 Th- light di~trlbutlon m-an~ 24 d-liv-r~ ~ight (8) chann-ls o~
test light (r-pr-~-ntativ-ly shown in FIGURE 1) ~~quentially to the ~aupl-~ in ~ colu~n of eight (8) v-s-el- of th- ~ulti-a--ay plate 12 and d-liv r~ on- channel of refa~_n: light, used to ~ub~tantially ~li~inat- error~ in mea~ur~oent due to th- variatlons ov-r tl~ in light a~plitud- ~nitt-d fro~ th- light ~ourc- m-ans 22 A photod-t-ctor means 26 detect- and m-a-ure- both th- test 21~66~

light that ha- p~ through the vessels and the reference light Th- acqui-ition and control proc-qqor m-an- 14, coupled to th-- photod-t-ctor ~eans 26, provide~ electrical ou~y~ signal~ in a conv-ntional ann-r, in accordance with the r-ference light and the te-t light~
Th- photoaetric mea~urement system 10 include- a chamber mean~
16, having an op-n and clo~-d ~tate and an ~ntry/exit door 111, for hou-ing the multi-a~say plate 12 A plat- carrier mean- 20 r-c-iv--, p r~Fh- ally ~Uy~G~ and carrie- th- multi-a--ay plat-12 from a lo~tng po-ition remote from th- chamk r m-an- 16 to a mea~ure~ent station therein, sequentially advancing each column of ve-8-1- to th- m-a~urement station The chamber mean~ 16 and plat-carrier m-an- 20 op-rat- in a conventional manner A t-np ratur- COnLLO1 means 28, und-r CG ~~ol of th-acqui-ition and control yLc~ cr mean~ 14, maintain- the t-~p-rature- of th- fluid ~ample~ in th- aulti-a--ay plat- 12 at a uniforo l-v l pr---lected by a user Tho tQaporatur- control means 28 dir-ct- a heated air stream in a pred-t-rmined pattern to the und-r-id- of th- multi-a-~ay plate 12, and th-r-by provide-~ub~tantially unifor~ and rapid heating of the ~ampl-- to th-pr-d-t-r in d t--p-ratur-Th- c ntral yrc_~F~ing unit mean- 15 initializ-- the acqui-ition and COI~LO1 proc-~;~cr mean- 14, and th- user co~nunicat-~ ~ith the unit means 15 through th- usor interface comput-r 30 The u~or int-rfac- computer 30 contain- application 21~;8~
program~ which s~t measurement paramQters, perform analysis a~d di~play r--ult~ for tho user With r-f-r-nc- to FIGURE 2, th- photom-tric d~vic~ 10 produces a b-am of ~ ntially ~onochromatic light in th- foro of fla~h-s and d-liv-r- thi~ light ~eguentially to a plurality of light c~anr~l~, ~ight in this preferred embodiment, to ~-quentially illuminat- th- fluid ~ampl~s in th- multi-a-~ay plat- 12 An ~xcitation light sourc- 50, a X~non fla-h l~op in thi~
pr-f-rr-d ~ bodim-nt, ~mits light fla~h~ containing wav~l-ngth~
b-two-n at l-a~t 200 nanom-ter~ and 1100 nanom t~r~ Light from th- ~xcitation light ~ourc- 50 beam~ through an ap-rturo 51 limitlng th- llght arc to approximat-ly t-n d~gr-Q- (10 ) Thi-light th-n pa ~- through a ~ource lens 52, which focu~Q~ tho light through on- of a s~ri~s of filter~ 55, includ-d in a filter wh~-l 56, upon a ~onochromator, g~nerally de~ignat~d 54 Th- ~xcitation light ~ourc- 50, ap-rtur- 51, and sourco l-n- 52 coop-rat~ to d fin- th~ light ~ourc- moan~ 22 Th- ~ourc~ l~n~ 52, in thi~ pr-f-rr-d c~odim~nt, i~ a fused silica plano-conv-x l-n~ with a 12 7 milli~-t~r dia~tar, a 16 millin-t-r focal length, and an optical magnification of 1 ~he ~ourc- lon- 52 i- ~pac-d 32 millim-ter~ fro~ th- ~xcitation light ~ourc- S0 and 32 ~illi~-tar- fro~ th- ~onochro~ator 54 With r-f-r-nc- to FIGURE 16, th-r~ ar- ~-von (7) filt~r~ 55A-G
on th- filt-r wh--l 56 Th~ filt~r- 5SA-E pa~- light of wav-l-ngth~ in th- rang- of 250 to 380 nano~-tora (com~only r-f~rr-d to a- a UG 5 filt~r), 380 to 440 (BG 37), 440 to 530 (VG

- 21~668~ '' 6), 530 to 630 (OG 5so) and 630 to 750 (RG 645) Th~ remaining - filt-r- ~r- a Didynium gla~s filter 55F, us-d in th- initial calibration of th- monochromator 54, and a dark filt-r 55G, al~o us-d for e~libration The multipl- gla-s filter- 55 ~L~-l-ct rang-- of wavelengths received by th- monoehro~ator 54 to sub-tantially ~li~inat- broa~hand light ~ignal-, Q~p eially ~ub-har~onic- of the d--ired wavelength that oth-rwi~ would b p by th- nonoehronator 54 to contaminate th- light ~ Thi~
~ l-ction enabl-~ the monochromator 54 to ~~it wavel~ngth~ o~
~ub-tantially ~onochromatic light with a bandwidth of approximately 5 nano~t~r- over a rang~ of wavelength~ of gr-ater than two to on-, or fro~ 250 nano~-t-r- to 750 nanom-t-r- The Didy~iu~ gla~
filt-r 55F provide~ a precis-, narrow absorption wavelength us-d in th- initial vavelength calibration of th~ monoehromator 54 A low-pr---ur- ~ rcury-Argon lamp verifies th- ~p-etru~ of th- Didymium gla~ a~ a part of th- manufaeturing ~ befor- th-in-tallation of th- Didyoiu~ glass filt-r S5F into th- photo~-tric d-vie- 10 Two additional open filter po~ition- 55H and I are provid-d wh-r- th- us-r ean install filt-r~ for custo~ usag- For ~xa~pl-, th- u--r ~ay in~tall int-rf-r-neo filt-ra in ord-r to ~ et a light band that is l-ss than approximat-ly 5 nano~-ter~
Th- dark po-ition S5G of th- filter wh--l 56 i~ us-d to en~ur- that no light illu~inat-- th- reference photod-t-etor 64 during the ~-a~uro~-nt of r-f-r-ne- dark eurrent offs-t calibration Light ~nt-r~ th- monoeh~omator 54 through a ~onorhro~atic entrane- ~lit 53 to a eollimating/foeu~ing mirror 57 whieh refl-cts 2~&fi~ -and colliuat-- th~ light beam to a dirfraction grating 59 There th- light i- disp-r~-d at an angle with r-~p-et to th- grating 59 and th- wav l ngth of light pa-~d by th- ~onoehromator 54 i8 Ai~ ~n~-~t upon thi- angl- Th- di~p-rs-d light fall~ baek on thQ
colli~ating/foeu~ing mirror 57 which fo~l~ sub~tantially ~onoehrouatie light to an exit ~lit 63 Thi- ~lit 63, pr-f-rably foru~d by a ~-tal ~nd eap (not ~hown) whieh r-tain- th- fib-r- 58A
of th- optieal fibor S8, is r-ctangular in ~hapo, 0 7 nillim-ters by 1 3 ulll$--t-r- Tho individual optie rlb r- 58A ar- arrangQd in a r-etangular array at the exit ~lit 63 by th- ~ tal ~nd cap Alt-rnativ ly, th- out-r cladding of th- optieal fib~r 58 may b-forn d into th- ~xit ~lit 63 Th- filt-r wh--l SC, optical filtors 55, nonoehro~ator 54 and ~ntrance and ~xit ~lit~ 53, 63 coop-rat~
to d-fin- th- wav-l-ngth ~-lsction m-ana 23 Th- ou~ of ~onoehromator 54 provid~J light having a pr d-t-r in d, continuou~ly ~-lectabl-, ~ n~ wav l-ngth rang-within th- fir-t wav-l-ngth rang- provid-d by light ~oure- 50 In th- pr-f-rr-d ~ bodi~-nt di-elo~ed h-r-in, th- ~-eond wavol-ngth rang- ha~ a ~r~ rnin d bandpa~ width, d-fln-d a- th- wav-l~ngth width at on--half naxinu~ light tran~ ion, of about 4 to S
nano~-t-r- for all e~nt-r-band wav~l~ngth~ eontint~o~-ly ~-loetablo by th- u--r b~J-In 250 and 7S0 nano~-t~r- Th- ~-nd~a~- width ~ay b pr-d-t-rnin d wlthin a wid-r rang- of about 1 to 20 nanou-t-r~
by ehanging th- width of th- ~xit ~lit 63, a , by ~~ploying a ~-ehanieally ad~u~tabl- ~lit a~ th- ~xit ~lit 63 - 214~68~ '"
Th- optical fiber 58 includes nineteen (19) optical fibers, - ~ach 200 ~illi~ t-r- in diam-ter with a nu~-rical ap-rtur- of 0 22 arrang d at th- input in three (3) rows ot six (6), s-v-n (71, and six (6) tib r- Thi- ~ff-ctively d-tin-- a 0 7 ~illi~-t-r by 1 3 ~illiu t-r r-ctangular ~xit ~lit 63 Th~ ouL~u~ o~ th- optical fib r 58 i- configured as a circl- with a diam-ter ot 1 3 ~illi~ t-r- Light from output of th- optical fib r 58, which is ~itt-d ov-r a ~olid angl- of about ten d gr--~ plit by a bea~
splitt-r 60, a -~rP~ ~ r- window in thi~ pret-rr-d embodim-nt Th-b a~ ~plitt-r 60 split~ th- light into a t--t light that p~r~
through th- b au splitt-r 60 to a rotor assQ~bly 70 and a r-t-r-ncQ
light that r-fl-ct- fro~ th- b-a~ ~plitt-r 60 to a flat r-t-renc~
~irror 62 Th- r-f~r-nce mirror 62 r-fl-ct~ th- reterenc- light through ~ r-f-r-nc- l-n~ 66 to a r-f-r-nc- photod-t-ctor 64 ot th-photod-t-ctor ~-ans 26 Th- r-ferenc- l-n~ 66 i8 a bi-conv-x lens, ia ~ad- ot tu--d ~ilica, ha- a focal l-ngth ot 6 8 ~illi~-ter~, and ha- a dian t-r ot 6 8 ~illimet-r~
Th- int-n-ity ot light flash-~ ~~itt-d by th- Xenon fla~h light 50 ~ay vary a- nuch a 50% b twe-n 8UCC-~-iV- tla-h-- duo to variation- in th- ~n-rgy and path l-ngth Th- r-t-r-nc-photodet-ctor 64 ou~ an ~l-ctrical ~ignal repr-~ntativ- ot the a~plitud- ot th~--onochronatic light carried by th- optical tiber 58 tor ~~ch tla-h ot th- light excitation ~ourc- 50 Thi~
~l~ctrical ~lgnal i- u~-d a~ an inten-ity r-tar~nc- tor th~
L ~ n~- ot t--t light tran~nitted through ~a~pl-- in th- uulti-as-ay plat- 12 -- 214fifi8~
Th~ rotor 70 includes two substantially identical rotor ~ nirror- 72A and 72B to b nd the light by 180 d-gr--- and a rotor len- 74 to foeu- th- light beam betw-en th- rotor ~irror~ 72A and 72B Th- rotor nirror- 72a and 72B and th- rotor len- 74 aet to rQduc- th- ~pot ~iz- of th- light b an fro~ 1 3 ~illi~-ter dia~ ter at th- input of th- rotor 70 a~-mbly to 0 65 ~illin-t-r~ at the output ~h- r-duction in b au diamet-r within th- rotor 70 allow-~ub-tantially all of th- light to b- launeh-d at a ~olid angl~ of about 20 d-gr-e- into the reeeiving fib rs 76 of th- light di-tribution n-an~ 24, gr-atly e~aneing effiei~ney of te~t light tran~uitted through th- rotor 70 Car- i~ taken ~o that the te~t light i- not foe~ in ~ueh a way that it ax_et'~ th- num ric~l ap-rtur- of th- di-tribution optieal fib r- 76 whieh will aee-pt light over a ~olid angl- of about 24 de~L ~ 3 ~ .
~o-t ~xi-ting ~-thod- of redir-eting light into multiple eurvilinear ehann-l~ U8- bent or eurv-d fib r- to aeeo~pli~h the bend of th- light b an Pla~tie mat-rial- b nd readily into the reguired eurvatur-- but b low approximately 340 nano~-t-r~ mo~t pla-tiea ar- highly ab~orptiv- Material- that trans~it wav-l-ngth- of 1--- than approxi~at-ly 340 nano~-t-r- ar- diffieult to bend Furth-r, ~y-t-~ whieh rely upon optieal fiber- to bend light eannot by~th-ir natur- redue- the ~iz- of th- i~ag- to inerea~e ~~iei-ney A pri~ary featur- of th- rotor 70 as d--erib d i- that it u8ea air a~ the tran~ ion m diu~ An air m-diu~ enable- th- ~y~teu to redireet the light without th- high 21~6~
ab~orption lo~- of plastic materials and to incr~asQ efficiency of light tran~ ion by r-ducing th~ ~iz- of th- ou~u~ beam Th- rotor a~ bly 70 di-tribut-- th- t--t light to a dark chanr-l, to e~ rat- for off~et, or to on- of a ~-ri-- of optical 5 distribution chann-l~, a- determined by th- ~-qu-ne- in th~
~-a-ur-nont Th- optical distribution chann-l- ar- d-fin-d by the di~tribution optical fib rs 76, mad- of ~olid ~ilica or quartz, 1 ~illi~eter in diau-t-r, with a nu~ rical ap rtur- of 0 22 Light fro~ th- fib~r- 76 reflects off a te~t mirror 78, mad~ of MgF2 with lo a flat ~urfae-, into a ~ubstantially v-rtical t--t light dir-etion A t--t ap-rtur- 80 further limits th- nu~ rical ap rtur- of th-b a~, and a t-st l-n- 82 and t- t photod-tector l-na 86, ~aeh a bi-CG v-Y l-n-, fu~-d ~ilica with 6 8 millimet-r focal l-ngth and 6 8 nilli~ t-r dia~-ter, furth-r foeu- th- t--t light For ~a~- of illu~tration, FIGURE 2 shows only on- of th- eight ~ubatantially id-ntieal di-tribution optical fib r- 76, t-~t ~irrora 78, te-t ap ~LUL~ 80, t--t l-n--- 82 and te~t photodet-etor l-n--- 86 Th- ~eri-- of optieal di~tribution c~ quentially illu~inat- th- vultiplieity of ~ampl-- in th- ~ulti-a--ay plate 12 with t-~t light, ~ueh that each of a ~ultiplieity of sa~ples r-e-iv - t--t light havinq a sub~tantially id-ntical ~p etral di-tribution of light int-n~itie~ within th~ nA wav-length rang- provid-d by th- ~onoehro~ator 54 Tho photom trie d-viee 10 deaerib d provid-~ th- above te~t light eharaeteri-tie- to a ~ultiplieity of sa~ple~ in a multi-as~ay plat- within a ~hort p-riod of ti~ ~o that th- ~ingle mea-urem-nt optieal prop rtie- o~

96 ~ample eontained in a conventional 8x12 microplate ~ay be det~rnin-d in approximately 9 ~ Similarly, optical prop-rti-- o~ ~ueh 96 samples may b d-t-rmined kin-tieally with about 9 ~-eond- between repetitive optieal m~asure~ent~ on eaeh S sa~ple Furth-rnor-, such kinetie ~ a~urement~ of optieal ~L~rtie~ eted from within a eont~n~o~-ly variabl- wavelength rang- of 250 to 750 nanom-ter-, may b- ~ad- whil a~ple~ within th- nulti-a~-ay plate ar- agitat-d by r-p at d o-eillatory ~ov~-nt ~ith 1-~ than about 9 -e: Ol~dQ between ee~ation of agitation and final ~-a-ur-- nt A~ ~hown in FIGURE 1, th- photo~ trie d-viee 10 inelude~ agitator mean~ 20A of a con~_n~ional natur- for int-r~ittently vibrating th- multi-as~ay plat- 12 and mixing th-~a pl-~ Th- optieal fiber 58, bea~ ~plitt-r 60, r-ferene- ~irror 62, r-t-r-ne- l-n- 66, optieal di~tribution ehann-l- 76, and the rotor 70, ineluding rotor mirrors -72A and 72~, and rotor lens 74 eoop-rate to d-tine th- light distribution m-an~ 24 After pa~Jing through the ~ample~, the t-~t light eontinue~ to th- t-~t photod-t-etor- 88 The light di~tribution m-an- 24 ~~ploy- a ~ultiplieity ot individual optieal tiber~, arranged in a r-etangular array at th- ~xit slit 63 ot monoehromator 54, to pa-~t-at light v rtieally through a ~ultiplieity ot ~a~pl-- di-po~-d on th- uulti-a--ay plat- 12 to th- photodetQetor- 88 Th- ~ult~-aaaay plat- 12 is eontain-d in an aaaay plate eo~part~-nt 127 within th- eha~b~r m-an~ 16 Und-r co ~,ol ot th-p~._ or ~-an- 2S, th- ~ulti-a~ay plate 12 i~ ~ov-d ~ro~ the ro~ot- lo~ln~ ~tation into the eompartment 127 and th- door 111 i~

214668~
clo~-d I~portantly, each of t~e multiplicity Or samples receives te~t light having a ~ub~tantially id-ntical ~p-ctral distribution of light int-n-itie~ provided within the P~nA wavelength range of light provid-d by th- monochromator 54 In thi~ pr-ferred e~bodi~nt, th- ~tati-tical m-an wav-langth of light -n~ ~y will vary by 1--- than 0 1 nanometers in th- di~tribution optical fibers 76 In no ca--, for wav~l~ngth~ ~tw~n 2S0 and 7S0 nano~tQr~, will th- ~tati-tical nean wav~length of light ~n-rgy will vary by ~or- than 0 5 nano~ t-r~ in th- di~tribution optical fib rs 76 Wh-r- a ~aapl- within th- ~ulti-assay plat- 12 contain- a ~ub-tanc-ab-orbing or oth-rwis- affecting light tran~ ion (e g , light ~catt-ring or light refraction), at wav-length- betwe-n 2S0 and 750 nano~ ter-, th- ~ub-tantially identical ~p-ctral di~tribution of light int-n-iti-- d-liv-red to ~ach ~a~pl- on th- ~ulti-a~ay plat~
12 in-ur-- that a ~ub-tantially unifor~ re-ult of m-a-ur-d optical prop-rti-- w$11 b- ~yO~-d by the photo~etric devic< 10 Th-- ~
~ub-tantially id-ntical g~ al di-tribution ot light int-n~iti-~, fro~ 250 to 750 nano~-ter~ wav-l-ngth, d-liv-red to ~ach sampl- on th- uulti-a--ay plat- 12 i- ~nabl-d by th- d-ploym-nt of th- guartz optical fib r 58, a- a bundl- with r-ctangular ~hap-, at th- exit slit 63 of th- ~onochromator 54 Th- light ~o coll-cted is dir-ct d aa t--t light, sub-tantially ~nc~ang-~ in sp-ctral di~tribution by th- rotor a~--mbly 70, to th- optical di-tribution fib r- 7C
Unifor~ ~p-ctral light distribution by splitting of th-optical fiber 58 directly may b- employ-d a~ an alternativ-21~fi~3~
embodiu-nt of th~ pre~ent invention In thi~ case, each optical di-tribution ehann~l 76 will bQ as~oeiat-d wlth a b-aD ~pl$tt-r 60, a r-f-r-nC- ~irror 62, r-f~r~nc- l~ns 66, and a r-r~renc-photod-t-etor 64, along with thc r~quir-d photod-tcctor circuitry s Th- ~iupl--t ca-- involv-~ ~ight (8) ~ilica light di~tribution optieal fib r- of about 0 5mm dia- t~r, arrang~d in a lincar fa-hion parall-l to and e~ntQred within tha ~xit ~lit 63 In g-n-ral, h~w~r, tho distribution Or ~p ctral light int-n-itie~
d-liv r-d to ~aeh distribution optical fib r 76 will b~
lo ~ubatantially uor- unifor~ wh-n th- rotor 70 i~ ~mploy-d Eaeh Or th- optieal distribution chann-l- 76 corr-~pond- to a ~-ri-- of ~l-etrical ch-nr-l- including a t--t photod-t-etor 88 Th- r-f-r-ne- photod-t-etor 64 and th~ photod-t-etor 88 ar- ~ilieon photodiod~- with 9 6 ~illi~-ter activo ar-a and 150 picofarad-~unction capaeitane-, to d-t-et th- t~t light and provid- a r-pr---ntativ- ~l-etrieal ~ignal a- an v~L~ to a t--t ehann-l in an int-grator 342 Or th- ~l~etrieal ~-a-urc~-nt ~y-t~o 324, a~
~hown in FIGURE 4 A eonv-ntional 96-w-ll ~ieroplat- or oth-r multi-ao-ay plat-~ay b u--d to eontain oampl-- in thio pr-f-rr d ~~bodi~ nt of th-photo~-trie d-~ie- 10 ~n ord-r to m-a-ur- light tranJ~i--ion at wa~-l-ngth~ of l~-- than approximat~ly 330 nanom~tar~ a~, a ~p-eial nulti-a--ay plat- ~hould b uo-d in ord-r to in-uro ad quat- tran-par~ney in thi- ultra~iol-t portion Or th~
~l-etro~agn-tie ~p etru~ Multi-ao-ay plat-o ~ad- of quartz, 6~pph ~ r- or oth-r W -tranopar~nt mat-rial- ~ay ba u- d Such 21~668~
quartz microplate~ are av~llabl~ from Mol~culAr Devlc~ corporat~on of ~-nlo Par~, C~ ornia, ~9~, Part No- R1077 and R1076 In addition, ~ polyn~ric multi-a~ay plat~ which la adequately tr~nopar-nt ov~r th- ~ntire wavelength range or 250 to 750 s nanom-tor- i- de~cribed in cop~ndlng and comoonly own~d Serial No , ~lled concurr~ntly her~wlth and ~ntltl~d ~Ultravlolet Radl~tlon Tran-parent Hulti-A~ay Plat-~, Wltb r-r-r-nco now to FIGURE 3a, th~ photom-trlc devlce 10 includ-- an l~oth~rmal chamber 116 and a temp-ratur- control rOr malntainlng th- t~mperatura Or th~ ~ample~ ln th- multi-a~y plate 12 at a pr-d-t~rmlned level A ran 102 driv-- a~bi~nt alr through an ~nclo--d pl-nuJ 104 into ~ narro~ pa~-ag~way 106 about an alr-h~atlng ~l-a-nt 108, whlch heat- tha alr to ~ pr-d-t-rmlned t-~p-ratur- Th- air h~ated by th- alr-h-atlng ~lQm~nt 108 move~
into a poat-h-ating pa~sageway 107 and th-n through op-ning- in an lnt-rlor ba-- wall 109 to a ma~or po-t-h-atlng pl-nu~ 112 and a mlnor po-t-h-atlng plenum 113 An air tomp-raturo ~naor 110 in th- ~a~or po-t-h-atlng pl~nu~ 112 m-a-ur-a th- temp-ratur- o~ th~
h-at-d air ~o that th- air-h-ating ~l-m-nt 108 may b controll~d to provld- th- d--lr-d, pr~d-t~r~ln~d alr t~mporatur-Th- hoat-d alr contlnuo- rrom th- ma~or po-t-h~atlng pl~num 112 and mlnor po-t-h-~tlng planu~ 113 through ap-rtur-- 114 ln a ba~rl- 130, a- b at ~hown ln FIGURE 3b Tho ap-rtur~- 114 dir~ct h-at-d alr to pr-d-t-r~ln-d r~glon~ Or th- multl-a~-ay plat~ 12 S dl~po~d ln ~ multl-a~ay plat~ compartm~nt 127 locat-d abov~ t~

2 1 4 ~ 6 ~3 A
baffl- 130 Th- multi-assay plate compartment 127 is enclo~ed by -a top wall 101, door--ide wall 103, door _,po- ~ sid- wall 117, int~rior ba-- wall 109, a~ w-11 a~ by a front side wall 105, back ~id- wall 115 and th- clos-d door 111, a- ~hown in FIGURE 3b Th-5 ~ulti-a--ay plat- co~partment 127, in thi- pr-f-rr~d ~~bodi~ent, i~
th~rnally i-olat d from ambi-nt air by $n~ulation 134, on- quart-r inch ~1/4~) polyur-thane foam about the cha~b-r 116, ~xcept for the door--id- wall 103 and door 111 Th- door--id- wall 103 is in-ulat-d on th- inn-r ~urfac- facing th- compartm~nt 127 with on--~ixt--nth inch (1/16~) polyurethan- Th- door 111 i- form-d of Noryl-- (a~ manufa~u~ed by Gen-ral El~ctric Corp ) and i~ not in-ulat-d additionally Th- t-mperature of th- fluid sampl-- in the multi-as-ay plat-12 i~ maintain~d within a rang- of approximately plus or ~inu~ one lS half (1/2) d-gr-- C-ntigrad- in a typical laboratory ~n~ironmont of approximat-ly tw nty-thr-- (23) d-gre-~ C-ntigrad- Cool d air is guid-d by an air guid- 121 out Or th- multi-a-~ay plat- co~partm-nt 127 through an ~xit port 120 Th- door 111 allow- ~ntry and ~xit of th- multi-a--ay plat- 12 from the multi-a--ay plat- cospartment 127 in a con~-ntional ~ann-r.
Sol~-ntJ, ~uch a- wat-r, hydrochloric acid and nitric acid, in th- fluid ~a~pl-~ in th- multi-a-~ay plato 12 may ~vaporat- from th- fluid ~mpl-- and b- ab-orb d by th- hoat-d air ~o pr-v-nt con~n-ation of th~ olv-nt- within tho photo~ tric d-vic- 10, an int-rior wall h-ating ~l-m-nt 126, a- ~hown in FIGURE 3b, tog-th-r with a cha~b r wall t~mp-ratur- ~n~or 128 in th- int-rior ba-o 21~6~4 wall 109, ~aintain th- inside surface of th~ chamb-r 116, near the t-mp ratur~ or 128, at a pr-d-t-rmined hou-ing t-mperatur~
slightly (g n-r-lly fro~ 0 5 to 2 0~C and mor- g-n-rally from O s to 1 0~) gr-at~r than th- t-mp-ratur- of th- h-at~d air Th- fan 102, air-h-ating ~l~a-nt 108, air t-mp-ratur- ~-n-or 110, wall h-ating ~lem nt 126, chamker wall t-mp-ratur- ~enr,or 128, baffl-130, and th- a~-oeiat-d control circuitry d--eribed b low with r-f-r-ne- to FIGURE 4, coop-rat- to d-~in- th- t~mp-ratur- cG ~Lol m-an- 28 FIGURE 3b illu~trat-- one arrangem-nt of th~ ap-rtur-~ 114 in th- baffl- 130 Thi~ arrangement of th~ ap-rturQ~ 114 direet~ an ~ flow of h-at-d air to th- c-nter v----l- o~ th- uulti-a~ay plat- 12 (which hav- 1-8~ surrac- ar~a and con--qu-ntly h-at mor- ~lowly than th- out-r ve~ of th- multi-a-~ay plat- 12) 80 that all v~ of th- multi-a~ay plat- 12 will r-aeh a pr-d-t-r in~d te~p ratur- at an equal rate Th- ap~L~uL~ 114 may b- ~hap d and dir-eted a- nozzl-~ to dir-et heat-d air in d~ir-d dir-etion- Alt-rnativ-ly, th~ in~id- ap-,~u~ , dir-et-d to th-insid- v-~ , ean hav- a larg-r dia~-t~r than th- out~id-ap rtur--, dir-et d to th- out~id- v-~ o th- in-id- v~
r-e-iv- ~or- h at-d air than th- out~id- ve~--l- and ~o that all v----l- ~ill r-aeh th- ~quilibriu~ t~mp~ratur~ at an qual rat-FIGVR~ ~ illu-trat-- th- eleetrieal eo~pon-nt- of th-photou trie d-vie- 10, ineluding a 68000-typ~ v~ er, ~-uory and a~-oeiatad digital hardware Th- u--r eo~ounieat-- with a e-ntral ~ or (CPU) 300 through a k-ypad 301, a di-play 303, 21~8~
a print-r port 304, and a serial port 305 The CPU 300 initializes and o ~ol- th- acqui-ition and control p~ cr n-an- 14 through a ~c~.~ abl- logic d-vicc (PLD) 322, ~uch a~ manufa~uL~d by Alt-ra C~y~Lation of San Jos-, California Th- CPU 300, printcr s port 304, ~-rial port 305 and PLD 322 coop-rat~ to d-~in- th-~ al ~ ing unit mean- 15, and th- k-ypad 301 and di~play 303 coop rat- to d-fin- thc us-r int-rfac- conput-r 30 A control y~c~or 320 cG ~ol~ th- ~l-ctrical n-a~urement ~y-t-a 324 Th- ~l-ctrical mea~ur~m~nt ~y~t-~ 324 includc- a digital to analog co v_~--r (DAC) 325 usQd in th- calibration of th- photo~ctric devic~ 10, a s-rie~ of tc~t channcl- in an int grator 342, a r-f-r-nc- int-grator 340, a multipl-x~r 344, and an a~plifi-r/A~C 323 A ~-rie- of cight t-~t photodat-ctor~ 88 and a r-far-nc- photod-t-ctor 64 provid- ~l-ctrical signal p~ls-~
r-pr-~-ntativ- of t--t light and r-f-renco light fla-h-~ to th-~-ri-- of t--t r~ of th- int-grator 342 and th- raf-r-nc-intagrator 340, ra-p ctivcly Th- int~grator- 340, 342 int~gratc and provid- a~ o~ ignal~ th- r--poctiv cn-rgi-~ in th-al~ctrical pul~-- r-c-iv d fro~ th- t--t photod-t~ctor- 88 and rafar~nc- photodat-ctor 64, r--p-ctiv-ly Th- P~D 322, in r--pon--to th- control proco--or 320, timc~ start and co~plotion of th-int-gration provid d by tha int-grator- 340, 342 T~- nultipl-x-r 344 r-c-iv - th- int grat d ou~u~ ~ignal- fro~ th- int grator- in parall-l and ~ultipl-x-- th--- signal~ to ~-rial Th-anplifi-r/ADC 323 anplifi-- and co v~rt- analog ~ignal- fro~ th-nultipl-x-r 344 into digital signal- An ~loctrical channcl 21~66~
includ-- th- r~ference photod-tector 64 or the test photodetector ~ 88 and th- cGLL_.~o"~ng referenc~ int~grator 340 or int-grator 342 Th- r-f-r-nc- photodetector 64, test photod-t-ctors 88, and electrical ~~a-ur ment ~y~tem 324 coop-rate to defino the S photod-t-ctor ~ an~ 26 A t-~p-ratur- ~-ns- circuit 326 r-c-iv-- and a~plifi-~ th-uu~u~ of the ~l-ctrical signals rrou th- air temp-ratur- sensor 110 and cha~b r wall t-mp~ratur- s-n~or 128, which r-y~ nt th-temp-rature- of the heat~d air in th- narrow pa-sageway 106 and the int-rior ba~- wall 109, .c_~e tively Th- ampli~i~d ~ignal~ ar-provid-d a~ o~u~- to th- amplifier/ADC 323 Th- ~mplifi-r/aDc 323 furth-r a~pli~i~- and conv-rt- fro~ analog to digital for~ th-signal- fro~ th- t-~p rature sQns- circuit 326 acqui-itiOn and co ~ol ~ or 320 rec-iv-~ thes- ~ignal- fro~ th- amplifier/ADC
323 r-y~ ntativ- of the wall and air t-mp rature- and OU-~8 ~ignal- through a h-at-r driver 328 to wall h-at-r 126 and air h-at-r 108 to CG ~ol th- t-~p-ratur- of th- fluid 8~0pl-- in th-~ulti-a~-ay plat- 12 to a pr-d-termin-d l-v-l Th- acgui~ition and control ~rc~e!~Qr 320 op-rat-- in a co~ ntional ~ann-r (i) to control th- ti~- of th- fla-h-- ~aitt~d by th- ~xcitation light sourco 50 through an ~xcitation light sourc- pow~r ~upply 306, (ii) to control th- po~ition of th- filter wh--l 56 through a fllt-r wh--l driver circuit 31~ and filt-r wh--l steppor ~otor 308, (iii) to control th- diffraction grating 59 in th- ~onochro~ator S~ through a monochromator driv-r circuit 316 and a ~t-pping grating ~otor 310, (iv) to co,~rol th- rotor 70 through a rotor driv-r circuit 318 and a st~pp~r rotor motor 312, and (v) to cG ~Lol th- plat- carri-r ~-an- 20 through a plat~ carrier driv-r eircuit 334 and an ~tepper plate carrier motor 332 Th~
COI~LO1 proc--~or 320, excitation light ~ourc- pow-r supply 306, s filt-r wh-~l dri~er circuit 314, filt-r whe-l ~t-pp r ~otor 308, monochro~ator driv-r circuit 316, stepping grating ~otor 310, rotor driv-r cireuit 318, ~t-pper rotor motor 312, plat- carrier driver circuit 334, and ~t-pp r plat- carri-r ~otor 332 eoop-rat- tog-th-r to d-fin- th- aegui~ition and control ~rc~ or m~an~ 14 FIGUR~ S illu-trat-s th~ timing of th- int-grator 342 and r-f-r-ne- int-grator 340 in the electrical measurem~nt sy-te~ 324 Light fla-h-~ ar- e~itted by the excitation light ~ourc- 50 and d-liv-r d to th- ref-r-nc- photod-teetor 64 and test photod-t-ctor~
88 In wav-for~ 44, the referenc- photod-t-etor C4 and te-t photod-t-ctor 88 provido ~l-etrical pul~ L ~ ~ntativ- of th-light fla-h-a In wav-for~ 45, th- int-grator 342 and the r-f-r-nc- int-grator 340 int-grate and provid- an output ~ignal r-pr-~-nting th- total en-rgy ~L~ ent in tho ~l-ctrical pul~-~
provid d by th- photod-t-etor- In wav-foru 46, th- int-grator 342 and r-f-renc- int-grator 340 ou~u~ ar- sa~pl-d at ti~-~
d-t- A in-d frow th- PLD 322 b-fore th- ~leetrical pul-- at tim-"pr--fla~h~ wh-n th- ~n-rgy of th- pul~ till approxi~at-ly z-ro and again at ~poat-fla-h~ wh-n approximat-ly all th- ~n-rgy in th- ~leetrieal pul~- ha- b ~n integrated Th- ~ignal~ fro~ the int-grator 342 and ref-rene- integrator 340 are calibrated for offs-t in th- int-gration ~LOeq~ by ~ubtracting tha ~pr--flash~

~1456~4 r-ading fro~ th~ ~post-flash~ reading In waveform 46, a timing ~ignal z-ro- th- int-gr~tor 342 and th~ r-f-r-ne- int-grator 340 aft-r th- ~po-t-fla~h~ to prepar~ for th- n-xt pu18~.
So~ noi-- i~ alway- present to contaninat~ an ~l-ctrieal s ~-~ur-~-nt and th- pr-ei~ion and rep-atability of th- ~ ~surem-nt ar~ o-_d wh-n the nois~ is ~inimiz~d A b n-fit of the t~ hniqu- d~-crib d above, using a fla-h light, i8 that th- amount of noi-- eonta inating th- ~-a-ur-~-nt i- aeeu~ulat-d only during th- int gration tia , a~ compar-d to a t-~n1~u- u~ing a eontinuou light ~ourea, wh-n noise is aeeu~ulating at all ti~ ~ Th~
t~ -h~iqu- u~d in the pr-~-rred embodi~-nt r-A~ th- noi~- in th-a-ur~J-nt approxi~at-ly by th~ ratio of th- int~gration tim- to th- eyel- ti~-FIGURES 6, 7, 8, 9, 10, 11, 12, and 13 b low illu~trate thes-qu-ne- of op ration~ involved in a ~-qu-ntial ~ a~ur-~ nt of th~
optieal prop rti-~ of tho ~amples in v-~ in th- aulti-a~-ay plat- 12 aeeording to th- pre~-nt inv-ntion FIGURE 6 i~ a flow ehart illuatrating th- ~-gu-neo und-rgon- by tha photo~-trie devie-upon pow r-up St-p 140 u~-- an iterativ- proe-~ und-r cGn~Lol of th- aequi-ition and ec L~ol ~ e-~or 320 to align th- rotor 70 to ~axi-iz- th- light trana~itt~d through th- optieal di-tribution ehann-l-In ~tap 142 th- eoar~- ~dark eurr~nt~ of~-t ealibration- ar~
d~t-r~in~d Dark ~r~nt i~ th- appar-nt light that th- ~l-etrical m-a-uran nt ~y-t-~ 324 r~ad- fro~ each of th- photod-t-etor- wh~n no light i- transDitt-d A dark eurr-nt off~-t ealibration is 2~6684 det-r~in-d ~or Qach in the series of t~t chann-ls in the integrator 342 for each gain setting in th- amplifier/ADC 323 St-p 142 ~lign- th- rotor 70 to a dark position wh-r- light do--not pa-- to th- ~-ria- of optical di~tribution chann-ls The DAC
325, included as a part of th- ~lectrical ~asur-~-nt ~ystem 324, i- ad~u-t-d to provid- a differential input ~ignal to ~ach in th-~-ri-~ of t--t eh-n~ in th- int-grator 342 wh-r- th- input ~ignal co~p nsat-- for th- ~ffect of dark ~ nt An it~rativ~
~rc~ und-r th- cG ~lol Or the acqui-ition and cG ~ol ~c~ or 320 iJ us d to find and ~tor- DAC 325 ad~ust~Qnt- that ~ini~iz- th~
appar-nt light ~-a-ur~m-nt in each of th- s-ries of optieal distribution ehann-l- and co~ ponding t-st chann-l- in th-int grator 342 for ~aeh gain ~etting of th~ a~plifi-r/ADC 323 and for th- r-f-r-ne- int-grator 340 Th- DAC 32S ad~ust~ nts ~o d-t-r~in-d ar- us-d as coars- dark c~k~_lL offs-t calibrations in th- ~oqu-ne- d-serib d in gr-ater d-tail in FIGURE 9 b low At st-p 144 th- wav-l-ngth of th- light ~-leeted within th-nonoehro ator 5~ is ealibrat-d A Didy~iu~ glass filt~r having a known wav l-ngth ab-orption ~p-etrum, ineluded in th- filt-r wh-el 56, i- u- d a- a wav l-ngth ealibrator within th- photo~-trie d-~ie- To ealibrat- th- wa~-l-ngth of th- ~onoehro~ator 54, st-p 1~4 turns th fllt-r wh--l 56 to tho po-ition wh-r- th- light r-e-iv-d by th- ~onoehro~ator 54 pA~g~ through th- Didyaiu~ gla--~ilter Th- angl- of th- monoehromator 54 in relation to th- light b an it ree-iv-s is then ad~usted by st-pping tho gratlng ~otor 310 und-r eontrol of th- eontrol proe-s-or 320 to ~ini~iz- th- light 2146~
d~t-et~d by th- r~f-rence photodetector 64 Th~ ad~ustment of the grating ~otor 310 ~tored in uemory i~ th- waval~ngth off~et calibration of th- ~onorhromator 54 St-p 1~6 ealibrat-- th- gain of th- a~plifi-r/ADC 323 Th-co~.ol p~cs~ r 320 ad~ust- th- DAC 325 to an ~l-etrical signal ~ ntativ of a pr-d-t-rmin-d light lav-l a- d-t-et-d by th-photod-t-etor- and ~ppli-~ thi~ l-v~l at th- input of th- firat in th- ~-ri-- of t--t ehann-ls of th~ int~grator 342 and at th- input of th- r-f-r~ne- int grator 340 Th- ratio of th- aetual ou~
fron th- ~l-etrieal ~asurement syste~ 324 to th- ~xpeet~d output i~ ~tor d in ~-~ory and u--d a~ a gain ealibration faetor of th-~l-etrieal ~ a~ur-~-nt ~y~tem 324 FIGURE 7 i~ a flow ehart illuQtrating th- g~n-ral ~-qu~ne- of op ration- aeeording to th~ inv ntion Th- ~-gu-ne- b gin- with th- initialization ~t-p 150 wh-n th- u~-r u~- th- k-ypad 301 or th- u--r int-rfae- eo~put-r 30 to ~-tabli~ng a ~ a-ur-~ nt protoeol and initiat- a m-a~ur~m~nt St-p 150 eonfigur~- th-photo~ trie d-vie- for ~nd-point, ~p~etru~, or kin-tie ~oa~ur-~ent~
and d-t-rain-- th- nu~b r and valu-J of th- wav-l-ngth-, ~p-etrum paran t-r~, agltatlon ti~- int-rval~, dor~ant ti~ int-rval~, v----l- to b- r-ad; and oth r ~i~ilar para~ t-r~
Agitatlon o~ th- ~ultiplieity of ~a~pl-- eontain-d in th-~ulti-a--ay plat- 1~ may b~ et~d by th- u--r for a pr d-t-ruin~d ti~ prior to d-t-rmining th- optieal prop-rti-~ of th- ~~apl-- Sa~pl- agitation, in both ~t-p lS2 and in ~t-p 156, i~ pro~ld-d by th- agitator means 20A, whleh inelud~ a 6 ~ ~
conventional 8t~ r motor and belt-driv~ mecbanism coupled to the ~ulti-a--ay plat- carrier mean~ that 6~p~G~g and fir~ly holds the nulti-a~-ay plat- and al-o lin-arly po~ition- th- colu~n~ of th-v~ l- in th- plat- above photod-t-ctor~ 88, a~ shown in FIGURE
3a, in a ~-qu-ntial fa-hion Th- agitator a-an- i~part- g-ntl-o~cillatory uotion a~ a linear di-plac-ment parallel to top wall 101 and int-rior wall 109 of th~ multi-a~ay plat- co~part~ nt 127, a~ shown in FIGURE 3a Th- amplitude ot lin-ar di-plac~ nt conpri~ing th- o-cillatory motion i- about 1/16 ot an inch at a ~-gu-nc- of alt-rnating fr-guenci-~ of about 20 Hz and about 30 Hz, ~ach gual p riod~ of approximat~ly 125 ~illi--:or~ Thi-sequenc- of alternating agitation fr~guencie~ i~ continu-d for a ti~- a~ ~hort a- 1 ~QC Dn~ Up to any l-ngth of ti~- ~-l-ct-d by th-u~-r which ay b a~ long a- 1 minute, 1 hour, 1 day, or 1 wo-k U-ually th- agitation iJ continued for i ~-cond~ to provide for ad-guat- ~ixing ot liguid ~amples of froa S0 to 400 aicrolit-r~ and having a vi-co-ity about the Jaa- a- wat-r at 23~C Th- agitation i~ tollowed by a pr-d-t~rmin~d delay tia- b-tor- th- ~tart ot the r-ad plata ~t-p lS~ Thi- d-lay tia- i~ ~-l-ctabl- by tha u--r within a ti~ aa ~hort a- about 200 ~ nd- to a~ long a- 1 ~inut-, 1 hour, or 1 day St-p 152 in FIGURE 7 agitate- th- aulti-a~-ay plat- 12 for tbe l~ngth o~ tia a- pr daternined in the initialization ~t-p 150 B-cau~- ~o~ ~ a~ur~a-nt~, including ~om- ~nd point ~-a~ur-~ nt~, will not r-guir- th- aulti-a~ay plat- 12 to b agitat d, ~t-p 152 i~ not alway- appli~d ~1~6~8~
st-p lS~ in FIGURE 7 6equenc-s through th- pr~determined wav-l~ngth-, optical di-tribution ~a~ and th- C6~L~ ~: .ding t~t chann-l- in tha int-grator 342, and column- of th- multi-a~ay plat- 12 to r-ad th- tran~mi~ion o~ light through ~ach pr-d-t-rmin-d v--~l and to calibrat- ~ach m a~ur~ment for dark ~L~'~ t o~f--t and 100% tran~mi~ion factor Th- r-ad plat- ~tQp 154 i- lllu-trat-d in gr-at-r d-tail in FIGURE 8 b low ~ ult$pl- r~ading- at multipl- tim int-rval- ar~ typically d--ir d ~or kin-tic m a ~lam-nt~, and th--- kin-tic m-a-ur~m-nt~
ar- ~ach accompli~h-d by multiple pa ~ - through th- flow chart illu-trat-d in FIGURE 7 End point and ~p-ctrum m-a-urem-nt~ ar-accompli-~-d with a ~ingl- pa~s Following th- r-ad plat- ~t-p 154, ~t-p 158 ch-ck- to d~t-rmin- if th- ~y-t-m ha- compl~t-d all of th- r-ading- in a pr-d-t-rmined kin~tlc r~ad cycl- If th-anaw-r in ~t-p 158 i~ no, step 156 optionally agitat-~ th~ multi-a~ay plat- 12 according to th~ protocol ~-t in initialization ~tep lS0 In at-p 156 a kin-tic ~ n~ typically includ-~ a fir~t tim~
int-r~al wh~r- th- ~ampl- li~ dornant, follow~d by an agitat$on tim- int-rval wh-r- th- ~ampl- i~ vibrat-d, ~ollow-d by a g~ :D .d tim~ int-rval wh-r- th- ~amplo li-~ dormant Each tim int-rval i8 pr-d-t-rmin d in initialization ~t~p 150 Wh-n ~t~p 156 complot-~, th- a qu-nc- r-turn- to ~t-p 154 for anoth-r r-ading in th- kinotic cycl- B cau~- ~om- maa~ur-m nts do not r~quiro agitation b twQ-n th- readinga, ~t-p 156 i- not alway- appli~d St-p- 158, 156 and lS~ ar- it-rat-d by th- sy~t-m until th- compl-t- kin-tic r-ading - 2l41j~8~

ha~ b-~n p rfor~-d If the ans~er in step 158 i~ ye-, th~ ~quence i- co~pl-t-FIGURE 8 ~~Yp~ the read plate ~t-p 154 to illu-trat- th~
~-qu-nc- of op ration- for r-ading th- colu~n- of th- multi-a~say s plat- 12 at ~ ct~d wavelengths st-p 160 align~ th- rotor 70 in a dark poaition wh-r- light i~ dir~ct-d ~o that no light illu~inat-- th- t--t photod-t-ctor- 88 St~p 162_r-ad- and ~tor~-in ~ aory, a ~ a-ur-m nt off~-t known a- ~dark ~L~nt~ for ~ach in th- ~-r$-- of t--t chann-l- in th- int-grator 342 for ~ach gain ~-tting and for th- r~f-r-nce int-grator 340 Tho r~-p ctiv- dark ~L~nt- ar- appliod to th- readings of th- sampl-~ tO CGLLe_~ for th- ~ffect of uoa~ur-m-nt offs~ts Th- s-quenco to m~a-ure and stor- th- dark ~LL ~nt- i~ de~crib d in gr-at-r d-tail with r-f~r-nc- to FIGURE 9 b low Step 16~ in FIGURE 8 r-ad~ and stor-~ into ~-mory the valu-s for 100~ tran~ ion for ~ach pred-t-rmin-d wavelength for ~ach of th- ~-ri-- of optical di-tribution chann-l~ and th- corra~pon~ng t--t chann-l- in th- int-grator 342 The r--p-ctiv- 100%
tran-~i~-ion valu-~ ar- applied to th- reading~ of th- te-t light tran-~itt-d th~ough t~- ~a~pl-~ in th- ~ulti-a~ay plat- 12 to calculat- th- fraction of t--t light ab~orb d by th- ~a~pl-~ Th-~ gu-nc- to ~ a~ur- and ~tor- th- 100~ tran~ ion valu-- i8 d--crib d in gr-at-r d-tail in FIGURE 10 b low St-p 166 ~ov-~ th- fir~t colu~n of v8s~-1- in th- ~ulti-a~-ay plat- 12 into po-ition above t~- t~t photod-t-ctor- 88 for L ~ ng A nini~u~ d-lay interval of about 240 ~illi--conda is - 21A668~

provid-d aft-r th~ linear po~itioning and before te~t light i8 d-li~-r-d to th- fir-t sample in a column ~o a~ to avoid sub-tantially any eff-et of settling of fluid ~anple~ within th-v ~ St-p 168 ~-lects the fir-t ~L ~ er~in~d wav-l~ngth 5 St~p 170 r-ad- ~ach of th- ~ 18 in th- column a~ illu~trat~d in gr-at-r d-tail in FIGURE 11 Step 172 ch-ek~ to d-t-rnin~ if all of th- ~r~ -t-rnin-d wav-l-ngth- hav- b--n r-ad If th- an~-r i~
no, ~t-p 174 ~-l-et- th- nQxt pr~d-t~rnin-d wav~l-ngth and L~LU~
th- ~ gu-ne- to ~t-p 170 A wav-l-ngth ~-l~etion ~an- inelud-~
lo ~onoehro~ator 54 whieh, in turn, inelud-- a CG~ ntional ~t-pp r motor and diffraetion grating driv~ moehani~ to aeeurat-ly po-ition dif~raetion grat~ng 59 to giv- 0 5 nanom-t-r wa~ ngth r-~olution for po-itioning light of a yL~ ct~d wav-length rang-at uono~hro~ator ~xit slit 63, as shown in FIGURE 2 Th-wav-l-ngth ~-l-etion ~ans providQ- for ~ff~eting st-p 174 within a tiu int-rval ranging from about 100 ~illi~J :n~- for ~all wav-l-ngth ~t-p~ of about 5 nanom-t-r-, to about 3 ~ nA~ for larg- va~-l-ngth ~t-p- of up to 500 nanom-t-r~ ( g , for po-itioning th- uon~ehro~ator fro~ 250 to 7S0 nano~ t~r~). Wh-n all wav-l-ngth~ ar- r-ad th- ~-qu-ne- go-a forward to ~t-p 176 to d~t-ruin- if all of th- pr---l-et-d eolu~n~ of th- ~ulti-a~-ay plat- 12 ar- r-ad If th- an~wer is no, ~t-p 178 mov-~ tha n-xt eolu~n of th uulti-a--ay plat- 12 into po~ition and L ~ t~ - th-~-qu-ne- to ~t-p 168 Wh-n th- uulti-as-ay plat- 12 is ~ov-d fro~ on- eolu~n to th-naxt, th- ~-ttling of th- ~a~ple~ may be eff-et-d and th- r-~ulting -- 21~66~

m-a~ur-nent of th- optical properties of th~ sample- in a ~inetic n-a-ur-- nt- ~ay bo changed Tb- pr-f-rr-d ~~bodi~nt illu~trat~d in FIGURE 8 ~~nc ~ through th- pr-d-t-r~in-d wav-l-ngth~ b ~or~
~-l-ctlng th- n-xt colu~n in ord~r to uiniuiz- th- nu~b r of ti~--s th~ ~ulti-a--ay pl~to 12 i8 ~oved An alt-rnativ ~~bodiment ~ nc~ through th- column~ bQfor- ~-l-cting th- n~xt wavelength Thi- alt-rnativ- ~-qu~nc- compl-te- in 1--- ti~ than th- pr-f~rr~d ~ bodir-nt Th- photo~tric d-vic- $- capabl- of op~rating in ~ith-r ~ bodi- nt FIGUR~ g -YpanA- step 162 to illu-trat- th- ~-qu-nc- of op ration- that calibrate the photometric d~vic- for dark ~LL~nt Th- dark ~L~nt i~ th- apparent light r-ad by th- ~l-ctrical ~a-ur-n nt ~y-t-n 324 wh-n no light i- trans~itt d A primary ~ourc- of dark curr~nt in th- photo~etric devic- i~ an inh-r-nt voltag- off--t in th- ~l-ctrical m-a-ur-~ nt ~y-t-~ 324 Each in th- ~-ri-- of t--t rh~n~ in th~ int-grator 342 i~ calibrat-d for ~ach gain ~-tting of th- a~plifi-r/ADC 323 and th- r-f-rQnc-int-grator 3~0 i~ calibrat-d and re~p-ctiv- calibration value- ar-~tor d in n*~ry Coar~- dark ~ nt off~-t c~libration~ w-r~
dot-rnin d and ~tor-d a- a part of th- pow-rup ~ qu-nc- d-~crib~d in FIGURE 6 abov~ Th- ~-qu-nco in FIGURE 9 d-t-r~in-~ r-~idual dark ~u,,~nt off--t calibration- that r-main aft-r th- coar-- dark ~ nt off--t calibration ha- b -n appliod and ~tor-- th-~
r~idual dark ~ off--t calibration~ in m nory ThQ
co~bination of th- coar-- and th- r--idual dark curr-nt 21A6684 ~' calibration- ~ub-tantially eliminate~ dark current error~ in t~e ~-a~ur- nt of ~aupl--Th- ~ qu-nc- in FIGURE 9 ~tart~ at ~t-p 180 which ~ cts a fir-t chann-l of th- int-grator 342 St-p 182 ~ ct- a gain of on- (1) in th- amplifi-r/ADC 323 At ~t~p 184 th- DAC 32S appli--th~ coar-- dark ~LL~ off-et calibration, d-t-rmin~d and ~tored in u uory during th- pow-rup ~-qu~nc- d--crib d in FIGURE 6, to th~
input Or th- ~ ct-d chann~l o~ th- $nt grator 3~2 Thi- coar--dark ~Ll. ~ offs~t calibration i~ approximat~ly ~qual and of oppo-it- ~ign to th- inherent voltag- offset in th- ~l~ctrical m~asur~ent ~yste~ 324 St-p 18C align- th- rotor 70 to a dark po-ition ~h-r- light do-~ not pa~- to th- ~-ries of di~tribution optical fib r~ 76 or to th~ t--t photod-t-ctor~ 88 Step 186 r-ad~ tho appar~nt t--t light lS for th- ~ ct-d chann-l of th~ int-grator 342 by subtracting th~
t~-t ~po-t-fla-h~ L~--1{ng from th~ te~t ~pre-flash~ r~ading as d~-crib d in gr-at-r d-tail in the ~l~ctrical timing diagram in FlGURE S abov- St-p 186 tak-~ nin- r-ading-, compute- th-av~rag-, and ~tor-~ thia a~ rag~ in memory a- re~idual dark curr~nt off~-t calibration Th- light ~xcitation ~ourc- 50 i~ fla-h-d in ~ach calibration r-ading ~o that a voltag- off--t in th- ~l-ctrical m a~urQ~-nt ~y-t- 32~ du- to radiat~d or conduct-d coupling into th- al~ctrical ~-a-ur~m~nt ~y~tem 32~ will app-ar in ths calibration ~ qu-nc- in th- ~am- mann-r a~ in a L~-~{nq of a t-st ~a~pl- in a n-aaur~-nt ~equ~nc~

214~68~
Th- te-t dark current is calibrated for each of the a plifi-r/ADC 323 gain- one (1), four (4), sixte-n, (16), and ~ixty four (6~) St-p 188 rh-ekQ to deternin- if all gains have been calibrat-d If th- answer io no, step 190 s-lect~ th- n~xt gain in the ord-r and ~ to ~t~p 184 I~ th- an-w~r in ~t~p 188 i~
ye-, ~t-p 192 Ch~ to determine if all th- test chann-lo in th-int-grator 342 hav- b-en ~-a~ured If th- an~w-r i~ no, otep 194 s-l-ct~ th- n-xt channel in the int-grator 342 and Ll~ tU~ th-~ quenc- to ~t-p 182 If the answ-r in ~tQp 192 io po-itiv-, th-~-qu-nc- i~ co~pl-t- and all of th- ch-nr l o~ th- int-grator 342 and all of the gains of the amplifier/ADC 323 hav- b-en calibrated for dark ~u~r~nt R-~-r-nc- dark curr-nt is calibrated u-ing a similar ~qu-nc-Th- filt-r whe-l 56 is moved to a dark po~ition wh-r- light does lS not pa-- to th- nclcchro~ator S~ or to th- re~-r-nc- photod-tector 64 R-f-r-nc- dark curr-nt is mea~ured by ~ubtracting the r-f-r-nc- ~pr--fla-h~ reading fro~ th~ referenc- ~po-t-fla-h~
~ y -~ ~ ng a- d--crib~d in gr-at-r d~tail in th- ~lectrical timing diagra~ in FIGURE S abov-FIGURE 10 -Yp~n~- ot-p 164 to illu-trat- th- ~ qu-nc- of op-ration- ln wh$ch 100% tran~ ion value~ ar- ~-aaured and stor-d for ~~ch pr d-t-r~in d wavelength for each of th- ~-ri-- o~
optical diatribution chann-l- and th- co~ ronA~nq t--t channelo in th- int gr~tor 342 Starting FIGURE 10 at ~tep 199 th- ~-quence ~ov-- th- plat- carri-r 20 wher- th- te~t light illu~inat-- the te-t photod-t-ctor~ 88 directly through air without pa~-ing through 214668ll the ~ulti-a--ay plate 12 Step 200 selQct~ thQ fir~t predetermined wav l-ngth St-p 202 aligns the rotor 70 to illu~inat- thc fir~t in th- ~-ri-- Or di~tribution optical ribers and sQl-ct~ th~ fir~t chann-l o~ th- intcgrator 342 Align~-nt Or rotor 70 rrOn a rirst S di~tribution optical ribor in th- ~ri-~ to th~ di~tribution optical rib r ln th- ~-ries requir-~ about 30 milll-~: QnA~ ~ which i ~6.~0.at-- both a ~oving pha~- and a ~-ttling ~pha-- St-p 204 r-ad~ an abaorption ror air a- ~hown in th- ~ a~ur-~-nt of d-~crib d in gr-at-r d~tail in FIGURE 12 b~low St-p 206 ~tore~
th- W~ ~ a-ur-d abov- a- wr~ Step 208 ch-cks to d~t-r~in- that 100% tran~ ion valu~- have been obtained for ~ach in th- ~-rie~
Or optical di~tribution channel~ and th- CG~ ronA in7 tQ~t chann-l~ in th- int-grator 342 If th< an~w r i- no, ~t-p 210 align~ th- rotor to th- next in the s~ries Or di~tribution optical rib r-, ~ ct~ th- n~xt in th- sQrie- of test chann-ls in the int grator 342, and L ~ tUL~-~ th- ~equenc- to ~tap 204 Ir the an~wor to ~tap 208 is y-~, ~t-p 212 rh~ to d-t-r~ln- ir all the pr-d-t-rnin-d wav-l-ngth~ hav- b~n read Ir th- an~w r i~ no, step 214 ~-l-ct- th- noxt wav l-ngth in th~ sequ-nc- and .~ tu. - to st-p 202 Ir th- an~w r to ~t-p 214 i~ y--, th- ~-qu-nc- i~ conpl~t~
FIGURE 11 -Yp-~d- ~t-p 170 to illu-trat- th- ~ qu-nc- o~
op ration- in~olv d in ~ d~ng a column Or ve~-l- in th- multi-a~aay plat- 12 B ginntn~ at step 220 th- CPU 320 dir-ct- th-rotor 70 to align th- t--t light to th- rir-t in th- ~-ri-- o~
di-tribution optical rib r~ 76 and th- acqui-ition and con~.ol proc-~or 320 ~ ct~ th- rirst in th- s~ri-~ or t~-t chann-l~ in th- $nt~grator 342 Step 222 reads the test light transmitted through a ~a~pl- in a selected vessel as de~crib d in gre_ter detail in ~ICURE 12 b low Step 224 eh-ek~ to d-t-r~ine i~ all o~
th- c~ hav- b en r-ad I~ th- an-w-r i~ no, ~t-p 226 align-s th- rotor 70 to th- n-xt in th- ~-ri-s o~ distribution optieal ~ib r- 76 Step 228 ~-l-cts th- n-xt chann-l in th- int-grator 342 and r-turn- th- ~-qu-ne~ to step 222 If th- an~-r to ~t-p 224 i~
y--, ~t-p 230 align~ th- rotor 70 to th- r$r-t in th- ~-ri-- ot di-tribution optieal ~ib~rs 76 to compl-t- th- ~-guene-FIGURE 12 -~rand~ ~t-p 204 and st-p 222 to illu~trate the ~-gu-ne- o~ op-rations involved in mea~uring the optie_l prop~rti-~
of a ~aupl- Th- ~-quence ~tart~ with step 240, illu-trat-d in gr-at-r d-tail in FIGURE 13 b-low, to optimiz- th- gain of th-~l-etrieal ~ a-urement system 324 Step 242 m-a-ur-- th- t--t light d-t-et d by th- test photodQteetors 88 and th- r-~erQnee light d-t-et d by the r-~-r-nc- photod-teetor 64 Th- ~xeitation-light ~oure- 50 ~nit- a sQrie- o~ light fla~h-~ Step 242 ~a-ures t-~t light tran~itt-d to the test photodeteetor~ 88, by subtraeting th- t--t ~po~t-~lash~ reading ~ro~ th- t--t ~pre-~lash~
~ ng and ~ a~ur-~ r-~-renc- light tran-~itt d to th- r-~er-nc-photod-t-etor 6~, by ~ubtracting th- r-~-r-ne- ~pr--~la-h~ r-ading ~ro~ th- r-~ r~ne- ~po-t-rlash~ reading Th~ ~ea~ur-n nt prc_ ~
i~ d--erib d in gr-at-r detail in th- el-etrieal ti~ing diagra~ in FIGUR~ S abo~ St-p 242 is r-peat-d 7 tim-~ and th- result~
su~n~d St-p 24~ eompute~ W~, an unealibrated reading o~ ab~orption o~ a ~a~pl- und-r t-~t, by dividing th- t-~t light ~-a~ur-d in ~t-p 214~684 242 by th~ r~f-renc- light ~-~-ured in step 242 Step 246 aligns tha rotor 70 to th- n~xt optical di~tribution chann-l St~p 248 coupl-t-- th- ~-gu-ne- by co~puting A, a calibrat-d ~ ng of ab~orption of ~ ~a pl- und-r t--t, by nultiplying th- unealibrated ~ , wr, by th- i v~ ~- of th- CGl~ A~g 100% tran~ ion valu- W~-, u-a~ur~d and ~tored in ~t~p 206 FIGURE 13 ~YpanA- ~tep 240 to illu-trat- th- ~-gu~nc- o~
op rat$on~ involv d in opti~izing th- gain Of th- ~l-ctrical u a~ur-a nt ~y~t-- 324 Four gain ~-tting~ ar- ua-d in th-auplifi-r/aDC 323 to giv- th- photo~-trie d-vie- a ~ a~ur~m nt rang- Of fiv ord-r~ of magnitud- wh-n ~-a~uring tho ab~orption of a ~aupl- If th- gain i- ~-t too high, ~aturation of th- eireuit~
in th- ~l-ctrieal ~ a~ur-m-nt ~y~te~ 324 will cau~- th- photo~otrie d-vie- to di~play an erron-ou~ r-aA~ng If th- gain i~ sot too low, ~l-etrieal noi~- will d-grad- th- praei-ion and ~-n~itivity Of th- r-ading Starting at ~t-p 260, th- gain of th~ _~plifi-r/ADC 323 i~ s-t to on- (1) St-p 262 ~-a-ur-~ th- t-~t light tran-~itted to th-t-at p~otod-t-etor 88 by ~ubtraeting th- t-~t ~po-t-fla-h~ r~ading fron th- t-~t ~pr--fla~h~ r~ading a~ de~erib4d in gr-at~r d-tail in th- ~l-etrie l tin$ng diagra~ in FIGURE S abov- St-p 264 rh~
to d-t-rnin if thia l-v l divid~d by on- h~ dk'~1 tw-nty ~ight (128) i- 1--- than th- full ~eal~ of th- a~plifiar/aDC 323 If th~
an~w-r i- y--, at-p 266 ~-t~ th- ampli~i-r/ADC 323 ehann-l gain to sixty four (64), th- ~oquone- i~ compl~t- and tho gain ha- bc-n opti~iz-d If th- an~w-r i~ no, ~t-p 268 eh-ek- to d-t-r-in- if 21~!~fi84 the l-v-l ~ a-ured in ~tep 262 divided by thirty two (32) is less than th- full ~eal- of the amplifier/ADC 323 If th- answer i~
y~ t-p 270 ~-t- th- amplifier/ADC 323 gain to ~ixt--n (16), th-~-qu-ne- i- eoupl-t- and th- gain ha- b--n opti~iz-d If th-s an-w-r i- no, ~t-p 272 eh-eks to d-t-r~in- if th- l-v-l u a~ur-d in ~t-p 262 divid-d by ~ight (8) i- 1--- than th- full ~eal- of th~
a~plifi~r/ADC 323 If th~ an-w-r is y-~, st-p 274 ~-t- th-a~plifi-r/ADC 323 gain to four (4), th- ~ gu-ne- i- eo~pl-t- and th- gain ha- b--n opti~iz-d If th~ answ-r is no, th- gain is l-ft at on- ~1) and th- ~ qu~ne~ i~ eo~pl-t-R-f-rring now to FIGURES 14 and 15, anoth-r pr-f-rr-d e~bodi~ nt of th- t~mperatur~ control m~ans 28 i~ shown Thi~
e~bodiu nt providos enh-nc~ temperatur- cc ~ol in th- foru of a ~or- uniforu rat- of h-ating from th- initial ~ntry t-~p-ratur- to th- pr---l-et-d ~-a-ur-~nt temperatur- and b-tt-r ~aint~n~--e of th- pr---l-et d t-~p-ratur- onc~ achi-v-d A uultiplieity of wall heating ~l~mont- and a--oeiat~d t-up ratur- ~-n-or- ar- plae-d in diff-r~nt r~gion- of th- wall- of ~ulti-a--ay plat- eo~part~nt 127 so a~ to er-at- s-parat-radiativ- h-ating zon-~ in th- eompartm nt A~ in th- pr-vioua ~-bodi~ nt, ~ub t~ntially all of th- wall- ~nelo-ing th- uulti-asaay plat- eoupart~ nt 127 hav a tcmp ratura gr~at-r than th~
t-~p ratur- o~ th air or oth-r conv-etion ga- pa~-ing through th-ap~rtur-- 11~ In thi- way, eond~nsation, within th- photo~-tric d-vie- 10 or on any eov-r (not shown) that may b plae d over ~ulti-a--ay plat- 12, i~ sub-tantially pr-vant-d T~- uultiplieity - 214fi~8~
Or h-ating ~l~m-nt~ and temperature-sensing elements may be di~po- d on any of th- wall~ ~nclo~ing th~ multi-a~-ay plate coupart nt 127, including top wall 101, intQrior wall 109, front ~ida wall 105, back ~id- wall 115, door--id- wall 103, or door-S ~F~ id- wall 117, or any othQr ~urfac- in ther~al co~aunication with on- or ~or- of th--~ wall~
Aa ~hown in FIGURE 14, thi~ pr-f-rr-d ~mbodiu-nt includ-~~-v~n (7) h-atlng ~l~antJ and ~ n (7) t-mp-ra~u~ n~ing ~l-u-nt~ plac-d, in pair~, at pre~-l-ct-d locationJ on top wall 101 A p-riph-ral wall h~ating elem-nt 402 and p~riph-ral wall t-np-ratura-~-n~ing el-~nt 422 ar- located n~ar th- v-rt-x of wall~ 101, lOS and 117 A p-riph-ral wall h-ating ~l-~nt 404 and p-riph-ral wall t-~p-ra~ 9 -ing ~l-m-nt 424 ar- locat-d n-ar tb- v-rt-x o~ wall~ 101, llS and 117 A p-riph-ral wall h-ating ~l-~ nt ~06 and p riph-ral wall t-mp~ra~k~ ~n~ing ~l-u nt 426 ar-locat d n-ar th- v-rt-x of wall~ 101, llS and 103 A p-riph-ral wall h-ating ~l-m nt 408 and p~ripheral wall te~p~ra~u~c aen~ing -nt ~28 ar- locat-d n-ar th~ v~rt~x of wall~ 101, 103 and 105 ~ inor c-ntral h-ating ~l-~-nt 414 and ~inor c-ntral t-~p-ratur--~-nJing ~l-u nt 43~ ar- locat-d imm-diat~ly abov- th- ~inor po-t-h-ating pl-nun 113 ~a~or c-ntral h~ating ~l~m~nt 412 and ~a~or c-ntral t- p ratur--a-n-ing ~l-n-nt 432 ar- locat-d i~o diat-ly abov- th~ or po~t-h-~t~ng pl-nu~ 112 Finally, a door heating ~l-a nt ~10 and a door t-~p ra~ n ing ~l-m~nt 430 ar- locat-d n-ar ~id- wall 103 and in th- vicinity of door 111 FIG~RE 14 also 2~461~
~how~ th- plac-~ent of the respective heat-r and ~ensor Qlements with r-~p et to th- te~t photodetectors 88 Th- h-ating ~ nt- are ~~t~ in the wall~ or door Th-inn-r ~all portion i- aluminu~ or oth-r ~uitabl- h-at cG lueting mat-rial ~ueh a~ braR~, steel, coppor, or tho like, and th- outer wall portion i~ th- in~ulation 134, a- d--erib d pr-viou~ly Th-t-~p ra~L~ ing ~lement~ are plac-d on th- ~urfae- of th- wall~
faeing ~ulti-a--ay plato 12 Direet radiativ- i~aging of the h-ating ~l-~-nt- onto th- sampl-~ i~ thereby ~ub-tantially avoided, and th- ~-n-or~ ~-n-- th- same wall t-mp-ratur- a- ~een radiativ-ly by th- ~a pl-~
Th- h-ating ~l<m nt~ ~ub~tantially r-due- ambi-nt teup ratur-~ff-et~ and add ~uppl-~-ntal radiativ- heating unifor~ly tl~o -J~o~t th- eo~part~ nt 127 Th- t-mp-ratur- ~-n-or~ 422, 42~, 426, 428, 430, ~32 and ~34 ar- eo~re ~-d to th- a~o~iato ~-parat- ehann-l~
of t-~p ra~ ing eireuit 326 shown in FIGUR~ 4 In thi~
o~bodiu nt, t-~p-ra~ nsing eircuit 326 ha- at l-a~t nin- (9) ~-parat- t-~pora~k~ ~-n~ing channol~ Th- multipl-x-d ou~ of eireuit 326 ar- l-d to a~plifi-r/ADC 323, whieh i- in el-etrieal eouaunieation with CGn~10l ~ t ~or 320 whieh, in turn, i~ in ~l-etrieal eo~aunieation ~ith h-ating ~l-~-nt eontrol eireuit 328 In thi- ~ebodi~ nt, h-ating ~l-~-nt control eireuit 328 al-o ha- at l-a-t nin (9) ~-parat- ou~yu~ chann-l~ A ~-parat- ou~ h~nn~l i~ eonn-et d to ~aeh of h-ating elem nt~ 402, 40~, 406, 408, 412 and ~14 in an ay~o~riat- ~a-hion so that heat-r 402 and ~-n~or 422; h-ater 404 and ~en~or 424; heater 406 and ~en~or 426; heater 21~6~
408 and -~- or 423; heater 410 and ~ensor 430; heater 423 and ~ ~n-or 432; a- w-ll a~ hQatsr 414 and ~ror 434 work tog-ther a~
pair~ in ~-v n (~) s-parat~ control loop- Th-~e ~-v-n ~-parat-eontrol loop- work in a ~imilar fa~hion to th- two (2) s~parat~
co ~ol loop pair~ for~Qd by wall h-at-r 126 and s~n~or 128, and by air h-at-r 108 and air t~mperatur~ -or 110, aa di~elo~d above and a~ ~hown in FIGURE 4 Th- nin- (9) ~-parat- t-~p-ratur~
CG ~ol loopa ar- co ~oll~d by ~t~n~-rd t--p-ratur- eireuitry a~
i- w~ known in th- art of temperatur~ co L~ol Th- ~ultiplieity of h-ating ~l-n nt- form a multiplicity of radiativ h-ating zon-~
within ~ulti-a--ay plate eompartment 127 and provid- for naintr~1ng a unifor~ st-ady-stat~ t-~p-ratur- in ~aeh of th~
~anpl-- eontain d in a ~ultiplicity of v~ on th- multi-a--ay plat-In y-t anoth-r pr-f-rred ~bodimQnt, ~aeh of h-ating ~l-~-nts 402, 404, 406, 408, 412, 414, and 126 may b- eG ~oll-d in a ~ingl-eo ~ol loop In thia ea~- th- r-lativ- pow-r eon-u~ption of th-r~p etiv- h-ating ~ -nt~ 402, 404, 406, 408, 412, 414, and 126 in th- pr-viou- ~ bodi~-nt i~ fir~t m-a-ur~d for a giv-n eonfiguration and eon-truetion of ehaib r ~ an- 16 with a giv-n plae-a-nt of th- h-atlng ~l~-nt~ 402, 404, 406, 408, 412, 414 and 126 into th-ir r--p~etiv- radiativ- h-ating zon-~ This m-a-ur-~ nt 1- av rag-d ov-r th- tim- r-guir d to h-at th- ~a~pl--of a nulti-a~-ay plat- fro~ roo~ temporatur- to 37 C, th~ latt-r whieh ia a fr qu-ntly utiliz~d final t-~p ratur- for bioeh-oieal m-a~ur-~-nt~ Th- r-lation~hip of h~ating pow-r eon~u~ d by th~

214~i~8~
heating ~l-~-nts, one with respect to the other, is adopted as a final fix d ~p-ci~ication for the r~lationship b-tw~-n each of the h~ating ~l-u nt~ In this embediment, a singl- temp-ratur- sensor 428 i- conn-ct d to an appropriate channel of t mp~ra~uL_ ~on~ing circuit 326 ~ho~n in FIGURE 4 to initiat- a ~o ~.ol loop Also in thi~ ~bodi~-nt, t~p~rature-~-n-inq circuit 326 ~ini~ally r-quire~
only two ~2) ~-parat~ t~peratur_ s~r-ing chann-l~, on- for CO~LO1 of air-h-ating ~l-~ nt 108 and on- for cG ~ol of h-ating ~l-m nts 402, 404, 406, 408, 412, 414 and 126 Th- multipl-x-d ou~u~- of circuit 32C ar- l-d to amplifier/A~C 323, which i~ in ~l-ctrical co~aunication with CG ~ol pror~er 320 which, in turn, i~ in ~l-ctrical co~ unication with h~ating ~lement CG ~ol circuit 328 In thi- ~~bodinont, hcating element con~.ol circuit 328 need only hav- two (2) ~-parat- o~-~u~ channels Tho a~ iat- ou~u~
chann~ conn-ct-d to th- air-heating ~lem~nt 108 and tho other to h-ating ~l~ont~ 402, 404, 406, 408, 412, 414 and 126 which may b- op rat d ~ithor in parall~l or in s-riQ~ A~ for thc previou~
~~bodiu nt, th- ~ultiplicity of h-ating ~l-~-nt~ form a ~ultiplicity of radiativ- h-ating zon-s within ~ulti-a~-ay plat-co~partu-nt 127 and provid- ror ~aintaining a uniforu ct-ady--tat-t-~p ratur- in ~ach o~ th- ~a~pl-~ contain-d in a ~ultiplicity Or v-~ on th- uulti-a--ay plate In th- pr-f-rr-d ~mbedi~nt, thc ap-rtur~ 114 in ba~ 130 ar- ad~uat d to c~ _~ntrato th~ flow of h-at-d coav~ ~ion air, or oth-r h-at-d in-rt con~ ~ion ga~ such a~ ni~Lo~n, argon, h-lium, carbon dioxido, or th- lik~, to pre~-lected region- o~ tho lower 214fiS8~
6urfac- of th- uulti-assay plate 12 Th- pre~ ct~d convection flow rat-- to pr~ ct~d region- of th- ~ulti-aJ~ay plat- further facilitat- a rapid uniforn h-ating rate and ~ub- qu~nt t-mp-rature ~ainttna-~ An ap-rtur- 114 is plac-d in dir-ct oppo-ition to each inn~r v-~-el o~ th- multi-a~say plat- 12 wh-n it i~ po~itioned abov- ma~or po-t-h-ating pl-num 112, a~ bo~t ~hown in FIGURES 3a and 15 Thu~ for 96-w-ll nulti-a~-ay plat--, having ~ixty (60) inn-r v-~ , $~ sl- which ar- not on th~ p ~ iph-ry, th~r-ar- 60 ap rtur-~ in th- portion of baffl- 130 ~ituat~d abov-ma~or po~t-h-ating pl-num 112 Th-~- ap-~u.~ ar- arrang-d in the ~am g-om tric patt~rn and 6pacing a~ th~ v~ within thQ 96-w-ll ~ulti-a-~ay plat- For exampl~, in a 96-ve~-1 multi-a~ay plat- having an 8x12 patt-rn with 9 m~ cont-r-to-c-nt-r ~pacing, ap-rtur-- 114 ar- arrang-d in an 6 x 10 pattern with 9 ~o center-to-c-nt-r ~pacing Th- ~iz- of th- apertures 114 also varieJ Th- inn-r 12 apQrtur-- ~52 hav~ about a 3 millimeter diam~t-r; th- p~nultimate inn-r~o~t 20 ap-L~r -, imm diat-ly ~ULLO~ 1n~ th- inn-r 12 ap rtur-~, hav a diam-ter of about 2 millim t-rJ Th- n-xt out-r~o-t 28 ap rtur-- hav- a diam-t-r of about 1 milli~ t-r Th-out-rno-t 36 v ---1~ of th- 96-well multi-as~ay plat- ar- not dir-ctly oppo-~d by any ap-rture 114 but h~at quickly du- to th-inh-r-ntly ~nhanc d p-riph-ral surfac- ar-a, a- di~cu--~d pr-viou~ly Ap~rtureJ 114 also ar- provided in th- portion ot batfl- 130 ~ituat-d abov- th- minor po~t-heating plenu~ 113, a- ~hown in 21~6~

FIGURE lS, in order to uniformly heat and maintain the measurement t-mp ratur- of th- ~ample~ within this region Ther~ ar- 30 such ap-rtur-- ~ituat d above the minor post-heating plenum 113 The diam t-r and placem-nt of these ape~ , one with re~pect to the oth-r, i- id-nt~cal to that o~ th- 30 ap-~ ituat-d above th~
ma~or po-t-h-ating pl-num 112 nearest to the t-~t photod-tectors 88, a~ ~hown in FIGURE 15 ~
Tog-th-r, th- radiative h-ating ~l-~ nt~, located to provide coordinat-d radiative heating zon-~, and th- modifi-d hsat di-tributing baffl-, CG~ trating heated air to th- central portion of th- ~ulti-a~say plate, cooperate to defin-radiativ-/col~ ~ion h-ating mean~, gen-rally d-~ignat-d 460 in FIGURE 14, for ~ub-tantially offsetting ambient effect~, re~l~c~g air circulation abov- th- samples and pre~erving sub~tantially unifora h-at di-tribution within the multi-as-ay plat- 12 The ~ampl-- contain-d ther-in ar- thus mor- rapidly and uniformly h-at-d to th- pr---l-ct-d temperatur- and temp-ratur- maint~n~r-~i- ~ub-tantially ~nh~r- ~
The abo~ d--cribed embodimQnt~ of th- present invention will p-rforn a ~ingl- m-a-ur-ment optical property analy~i~ of a microplat-, 8x12 v ---l-, in about 9 secon~ In a multi-a~-ay plat- wlt~ than tw-lv- columns, the tim- i~ r~
~o~o.Lion~t-ly Wlth ~equ-ntial repetition of ~uch m-a-ur-m-nt~
to d-t-r~ln- th- klnatically-changing optical prop-rtie- of the sa~pl--, the int-rval b twe-n ~uch repetitiv- m-a~ur-~-nt~ i~ about 9 ~-cond~, a ~p-ed pr---ntly unattainabl- in a photom-tric d-vic-21~66~ ' of this scop- ~nd ~xtent Optionally, th- sequent$al rep-tition of ~uch ~ a-ur-n-nt- ~ay include agitation step 156, which may be as short a- about 1 no~ ~ th-r-by i ~L~I-;ing tha tl~- interval sel-ctably to 10 ~-conds The optical prop-rti-s ~ay b uade at any wav~l~ngth of light, ~-l-ctabl~ by th- u--r in int-rval- of 1 nano~ t-r ~t-ps, ~ n 250 and 750 nanom t-r- ~o that a _~9_~L~m of optical prop rtie- of the multiplicity o~ ~a~ple- may b ~onitor d ln a kin-tic fashion, which optionally ~ay include agitation ~t-p 156 Optical yL~p~rtie- m~a-ur-d by photo~etric d-vic-a incG~yGLating th- disclosed invention includ- light abaorbanc-, light ~catt-ring, fluor-~c-nc- and/or pho-phoL-~enc~
Whil- pr-ferred ~mbodiments of th- present invention havo b -n shown and d-scrib d, it will bo appar-nt to tho-- ~kill d in th-art that variou- chang-~ and modification~ may b ~ad- without departing fro~ th- tru- scop- and spirit of th- pre~ent invention For that L~ on, th- ~L~nt invention i- d-fin d by th- following clai~J

Claims (37)

1. A photometric device for measuring an optical property of a plurality of samples, contained within a plurality of vessels in a multi-assay plate, comprising, in combination:
an excitation light source that emits a first light having a first wavelength range;
a monochromator, responsive to said first light received from said excitation light source, for producing a second light having a predetermined second wavelength range within said first wavelength range;
an optical fiber, coupled to said monochromator and extending in a first direction therefrom, for receiving said second light and transmitting a test light substantially in said first direction;
a distribution network including a series of distribution optical fibers extending in a second direction;
rotor means for receiving said test light from said optical fiber and for redirecting said test light substantially in said second direction and sequentially into each of said distribution optical fibers;
said rotor means including at least a first mirror operable in a series of mirror positions in correspondence with said series of distribution optical fibers, respectively;
said distribution network transmitting said test light substantially vertically and sequentially through said vessels, said test light being affected by each of said samples to produce a plurality of measurement light flashes; and photodetector means for receiving said measurement light flashes and responsively providing a plurality of electrical measurement output signals representative of said optical property for each of said samples, respectively.
2. A photometric device as claimed in claim 1 wherein said rotor means includes a second mirror and a lens interposed said first mirror and said second mirror.
3. A photometric device as claimed in claim 2 wherein said first and second mirrors and said lens are mechanically linked and move in unison.
4. A photometric measurement device as claimed in claim 3 further comprising:
plate carrier means for intermittently advancing and vibrating said multi-assay plate; and microprocessor means, coupled to said rotor means, to said monochromator, to said photodetector means and to said plate carrier means, for controllably activating said plate carrier means, controllably sequencing said rotor means through said mirror positions, selecting said second predetermined wavelength range, andanalyzing said electrical measurement output signals.
5. A photometric device as claimed in claim 1 further comprising temperature control means, substantially enclosing said multi-assay plate in a closed state, for regulating the temperature of said samples during measurement.
6. A photometric device as claimed in claim 5 wherein said temperature control means includes supply means for generating a stream of heated air and a baffle, interposed said multi-assay plate and said supply means, for distributing said heated air in a predetermined pattern upon said multi-assay plate.
7. A photometric device as claimed in claim 6 wherein said supply means includes a heater and a fan for moving ambient air over said heater to provide said stream of heated air and wherein said baffle includes central apertures and peripheral apertures, said central apertures being larger than said peripheral apertures.
8. A photometric measurement device as claimed in claim 7 further comprising:
plate carrier means for intermittently advancing and vibrating said multi-assay plate; and microprocessor means, coupled to said rotor means, to said monochromator, to said photodetector means and to said plate carrier means, for controllably activating said plate carrier means, controllably sequencing said rotor means through said mirror positions, selecting said second predetermined wavelength range, and analyzing said electrical measurement output signals.
9. A photometric device as claimed in claim 1 wherein said excitation light source includes a flash lamp providing a series of first light flashes, said test light including a series of test light flashes corresponding thereto.
10. A photometric device as claimed in claim 9 further comprising beam splitter means for diverting a portion of each of said test light flashes to provide a corresponding series of reference light flashes and for delivering said reference light flashes to said photodetector means.
11. A photometric device as claimed in claim 10 wherein said beam splitter means interposes said optical fiber and said rotor means.
12. A photometric device as claimed in claim 11 further comprising:
temperature control means, substantially enclosing said multi-assay plate in a closed state, for regulating the temperature of said samples during measurement, said temperature control means including supply means for generating a stream of heated air and a baffle, interposed said multi-assay plate and said supply means, said baffle having central apertures and peripheral apertures directing said heated air against said multi-assay plate and about said vessels; and microprocessor means, coupled to said excitation light source, to said rotor means, to said photodetector means and to said temperature control means, for controllably activating said flash lamp, controllably sequencing said rotor means through said mirror positions, analyzing said output signals in accordance with said reference light flashes, respectively, and controllably activating said supply means.
13. A photometric device as claimed in claim 1 wherein said first wavelength range is a continuum and said monochromator includes a ruled grating and slit means for providing said second wavelength range for receipt by said optical fiber.
14. A photometric device as claimed in claim 13 wherein said excitation light source includes a flash lamp providing a series of first light flashes, said test light including a series of test light flashes corresponding thereto, said photodetector means including a reference photodetector.
15. A photometric device as claimed in claim 14 further comprising splitter means for diverting a portion of each of said test light flashes to said reference photodetector as a series of electrical reference signals.
16. A photometric measurement device as claimed in claim 15 further comprising:
plate carrier means for intermittently advancing and vibrating said assay plate;and;
microprocessor means, coupled to said rotor means, said monochromator, said photodetector means and said plate carrier means, for controllably activating said plate carrier means, controllably sequencing said rotor means through said mirror positions, setting said second wavelength range, and analyzing said electrical measurement output signals in accordance with said electrical reference signals.
17. In a photometric device of the type utilizing a multi-assay plate and an optical fiber for transmitting light from a source in a first direction, the improvement comprising, in combination:
a series of distribution optical fibers extending in a second direction; and rotor means, including at least a first mirror having a series of operational positions, for receiving said light from said optical fiber and for redirecting said light sequentially along each of said distribution optical fibers, said operational positions being in correspondence with said distribution optical fibers, respectively.
18. The improvement as claimed in claim 17 further comprising a second mirror in fixed relationship to said first mirror and a lens interposed and in a fixed relationship to said first and second mirrors.
19. In a photometric device for measuring an optical property of a multiplicity of samples contained in vessels of a multi-assay plate, an improved temperature control means comprising:
chamber means, having chamber walls defining a post-heating plenum and a multi-assay plate compartment, for substantially enclosing said multi-assay plate; and supply means for providing a stream of heated air to said multi-assay plate compartment, said supply means including a baffle having a plurality of apertures for directing said heated air against said multi-assay plate and about said vessels to heat said samples at a substantially uniform rate and to maintain said samples at a substantially uniform temperature.
20. An improved temperature control means as claimed in claim 19 further comprising wall-heating means for heating said multi-assay plate compartment.
21. An improved temperature control means as claimed in claim 20 wherein said wall-heating means includes a plurality of resistive heating elements on said chamber walls in a predetermined zone pattern for heating said chamber walls and for cooperating to maintain saidsubstantially uniform temperature.
22. An improved temperature control means as claimed in claim 19 wherein said supply means including a heater and a fan for moving ambient air over said heater to said post-heating plenum, said baffle interposing said post-heating plenum and said multi-assay plate compartment and including a series of central apertures and a series of peripheral apertures, said supply means and said wall-heating means cooperating to define a temperature/humidity regulator.
23. An improved temperature control means as claimed in claim 22 wherein said central apertures are larger than said peripheral apertures.
24. An improved temperature control means as claimed in claim 22 further comprising microprocessor means for controllably activating said temperature/humidity regulator.
25. In a photometric device of the type utilizing a multi-assay plate includinga plurality of samples in a plurality of vessels, an improved means for generating a test light, to be transmitted sequentially and substantially vertically through said vessels for receipt by photodetector means, comprising in combination:

a flash lamp;
a monochromator, responsive to said flash lamp, for producing a series of test light flashes, defining said test light, having a predetermined wavelength substantially within at least the range of 250 nanometers to 750 nanometers;
an optical fiber for receiving and transmitting said test light flashes;
distribution means, coupled to said optical fiber, for distributing said test light flashes through said plurality of samples; and splitter means, interposed said first optical fiber and said distribution means,for sampling each of said test light flashes and for providing a reference relating thereto to said photodetector means.
26. An improved means as claimed in claim 24 wherein said flash lamp is a xenon lamp.
27. A photometric device as claimed in claim 25 wherein said test light is a continuum and said monochromator includes slit means for passing a predeterminedportion of said continuum for receipt by said optical fiber.
28. In a photometric device for measuring an optical parameter of a plurality of samples, contained within a plurality of sample sites disposed on a multi-site assay plate, of the type including:
an excitation light source for providing test light to eight or more of said sample sites;
a light distribution network, including a series of distribution optical fibers, for transmitting said test light substantially vertically through two or more of said sample sites;
a plurality of photodetectors for receiving emitted light from said eight or more sample sites and providing electrical signals relating to the intensity of said test light as passed by said two or more samples;
vibrating means for imparting repeated oscillatory movement of said multi-site assay plate for a predetermined time before each of a series of at least two measurements of said optical parameter at said two or more sample sites; and means for kinetic analyzing said electrical signals;
the improvement comprising;
monochromator means for receiving excitation light from said excitation light source and for transmitting a preselected wavelength bandpass fraction thereof, defining a mean wavelength, to said light distribution network; and coupling means for coupling said monochromator means to said light distribution network such that said mean wavelength of said test light delivered to each of said eight or more sample sites varies by less than one nanometer.
29. The improvement as claimed in claim 28 wherein said mean wavelength is between 250 and 750 nanometers.
30. The improvement as claimed in claim 29 wherein said monochromator means includes a diffraction grating.
31. The improvement as claimed in claim 30 wherein said monochromator means further includes a light-emission slit, said light distribution network including a plurality of optical fibers coupled to said light-emission slit.
32. The improvement as claimed in claim 31 wherein said photometric device includes a series of reference photodetectors, each of said optical fibers beingassociated with one of said reference photodetectors, respectively.
33. The improvement as claimed in claim 30 wherein said coupling means includes rotor means for distributing light sequentially to each of said plurality of optical fibers.
34. The improvement as claimed in claim 30 further comprising a multi-assay plate compartment for substantially enclosing said multi-assay plate and for maintaining said samples at a substantially uniform predetermined temperature during measurement of said optical parameter.
35. The improvement as claimed in claim 34 further comprising temperature control means for providing a stream of heated air to said multi-assay plate.
36. The improvement as claimed in claim 35 wherein said temperature control means includes:
air-heating means for providing said heated air;
air-compression means for compressing said heated air;
a plenum for storage of said heated compressed air; and a baffle, interposed said plenum and said multi-assay plate, having apertures distributing said heated compressed air in a predetermined pattern upon said multi-assay plate.
37. The improvement as claimed in claim 36 wherein said flash lamp is a xenon flash lamp.
CA002146684A 1994-04-15 1995-04-11 Photometric device Abandoned CA2146684A1 (en)

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US20030081207A1 (en) 2003-05-01
US6151111A (en) 2000-11-21
US6693709B2 (en) 2004-02-17
EP0677732A2 (en) 1995-10-18
JPH0882594A (en) 1996-03-26
EP0677732A3 (en) 1996-06-12
US5557398A (en) 1996-09-17

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