WO1999049974A1 - Dispositif sous forme de plaque servant a contenir de petits volumes de liquide - Google Patents

Dispositif sous forme de plaque servant a contenir de petits volumes de liquide Download PDF

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Publication number
WO1999049974A1
WO1999049974A1 PCT/US1998/006368 US9806368W WO9949974A1 WO 1999049974 A1 WO1999049974 A1 WO 1999049974A1 US 9806368 W US9806368 W US 9806368W WO 9949974 A1 WO9949974 A1 WO 9949974A1
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WO
WIPO (PCT)
Prior art keywords
wells
die
plate
microwells
approximately
Prior art date
Application number
PCT/US1998/006368
Other languages
English (en)
Inventor
Kevin R. Oldenburg
Gregory F. Hollis
Thomas D. Y. Chung
Original Assignee
The Du Pont Merck Pharmaceutical Company
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 The Du Pont Merck Pharmaceutical Company filed Critical The Du Pont Merck Pharmaceutical Company
Priority to PCT/US1998/006368 priority Critical patent/WO1999049974A1/fr
Priority to AU67911/98A priority patent/AU6791198A/en
Publication of WO1999049974A1 publication Critical patent/WO1999049974A1/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates

Definitions

  • the cu ⁇ ent invention is directed to an apparatus for holding small quantities of liquids, such as a microtiter plate.
  • liquid refers to pure liquids, as well as liquids containing paniculate matter and solvents containing solute.
  • the compound is then exposed to the target of interest, usually ⁇ a purified protein such as an enzyme or receptor but also possibly a whole cell or non-biologically derived catalyst.
  • the interaction of the test compound with the target is generally measured radiochemically, spectrophotometrically, or fluorometrically.
  • fluorescent probes have been developed which are substrates for enzymes or calcium indicators, pH indicators, amine-reactive or carboxylic acid-reactive, as discussed in the Handbook of Fluorescent Probes and Research Chemicals, 5th ed., R. Haugland and Karen Larison, editor, published by Molecular Probes, Inc., 1994.
  • Radiochemical measurement is usually considered the most sensitive of the detection methods, followed closely by fluorescence.
  • the problems 2 associated with using radioactive material such as exposure limits, record keeping, and waste management, make this detection method significantly less attractive than detection by florescence. Consequently, the fluorescence measurement technique has gained wide spread acceptance.
  • the fluorescence measurement technique light of a given wave length is directed onto a sample within the well of a microtiter plate. A portion of this light is absorbed by the sample and reemitted at a different, typically longer, wave length, which is then measured.
  • Instrumentation for fluorescence detection is based on conventional 96-well plates. Such instrumentation is available from Dynatech Laboratories, 14340 Sullyfield Circle, Chentilly, Virgina 22021, and
  • the wells of conventional 96-well plates typically have volumes of approximately 400 microliters each.
  • the wells typically have cylindrical walls and either flat, round, or V-shaped bottoms.
  • the plates are conventionally made from a white or black plastic, such as polystrene, polypropelene, or ABS, that has relatively low intrinsic fluorescent properties. While this low level background fluorescence from the plate material is undesirable, it usually presents no major problems in fluorescence detection studies since the fluorescence from the sample in the well is generally orders of magnitude greater than the background fluorescence from the plate. This difference in fluorescence between the plate material and the sample is due both to the large volume of the sample in the well, usually 50-200 microliters, as well as the low surface area to volume ratio of the well in the plate.
  • combinatorial chemistry libraries are made by the sequential addition of small organic building blocks onto an organic scaffold.
  • the scaffold is covalently linked to a solid support structure, such as a Tentagel resin, via an acid, base, or photo-cleavable linker.
  • solid supports structures are commonly referred to as "beads" and encompass structures having a variety shapes and sizes. In general, each bead, which is approximately 130 microns in diameter, contains 100 to 200 picomoles of compound. The small amounts of compound found on a single bead requires that the assay of the compound on that bead be perfo.rmed in small volume.
  • the concentration would be 500 nanomolar, assuming a molecular weight of 500 daltons. This concentration is significantly below the ideal concentration of 10 micromolar that is generally used for screening compounds for biological activity. Also, it is generally desirable to be able to screen the compound at least twice so that the results CM be confirmed if the compound tests active in the first assay. In order to reach die 10 micromolar concentration or to screen the compound at least twice, and have enough left over for determination by mass spectroscopy, the compound should be cleaved into less th.an 5 microliter.
  • assay miniatu.rization creates a number of problems. Reducing the size of the wells increases the difficulty associated with accurately dispensing liquids into diem because it becomes increasingly difficult to locate the dispensing device precisely over the center of each well. Inaccurate locating of the dispensing device will result in liquid being dispemed onto the boundary between wells, rather than into the wells themselves. Unfoitunately, the wells of conventional microtiter plates are separated by flat, horizontal surfaces upon which liquid can collect if it is not accurately dispensed into the wells. The collection of liquid between wells can create a variety of problems, including partial filling of wells, loss of reagents, and inaccurate mixing and concentration of components.
  • a microwell having a volume of 0.5 microliters will produce a signal that is only 0.1 to 0.2% of the signal resulting from the use of the well of a conventional 96-well plate.
  • Accurate measurement of fluorescence is also complicated by me intrinsic fluorescence, in at least one region of the spectrum that is useful for detection of biological reactions, of the plastics from wh ⁇ cTT microtiter plates have conventionally been made, as previously discussed. The effect of .such background fluorescence is exacerbated in small volume microwells because the well surface area to volume ratio is significantly greater than in conventional 96-well plates.
  • fluorescence measurements benefit from plate materials having minimum intrinsic fluorescence
  • different screening technique benefit from the optimization of other properties of the microtiter plate material.
  • Such optimization is important when using small microwells.
  • spectrophotometric techniques light of a given wave length is directed onto the s.ample -and die .amount of light diat passes through the s.ample is detected. Consequently, in d is application, it is desirable for the microtiter plate wells to be as tr ⁇ uispjirent as possible so as to minimize the interference with the transmitted light.
  • Luminescence measurements are also used to perform biological assays. In this technique, die light generated by die s£imple _ is ' etected. Since the amount of light generated is relatively small, it is desirable that the microtiter plate material provide as high a reflectance as possible so as to maximize the signal.
  • This and odier objects is accomplished in an apparatus comprising a plate in which a plurality of adjacent microwells are formed, each of the microwells having (i) a bottom, (ii) at least one side wall, and (iii) an opening for receiving a liquid.
  • the walls of each two adjacent microwells intersect so as to form an upward facing edge, the edge defining d e boundary between the openings of me adjacent microwells.
  • the widdi of each edge is no greater than approximately 250 microns, the radius of curvature is no greater than approximately 150 microns, and the maximum widtii of any hoiizontal surfaces formed on the edges is less dun approximately 80 microns, and the plate is formed from a liquid crystal polymer.
  • the invention also encompasses a mediod of screening .an agent for biological activity comprising die steps of (i) suspending a plurality of beads in a solvent so as to form a bead containing suspension, (ii) pouring the suspension onto a plate having a plurality of microwells, each of which has a bottom, at least one side wall, widi side walls of adjacent microwells intersecting so as to form an upward facing edge, and an opening for receiving the suspension, with openings of adjacent microwells separated by a boundary defined by die edge, whereby a portion of the solvent enters each of d e microwells, (iii) allowing the suspended beads to settle into the microwells so that at least one of the beads is suspended in me portion of the solvent in each of die microwells, (iv) removing the solvent, and (v) applying die agent onto die plate.
  • Consequendy .another embodiment of the invention comprises a microtiter plate in which each of die side walls of die wells has a first portion that forms .an opening for receiving liquid .and diat is inclined at an angle to die vertical direction, and a second portion diat extends essentially in the vertical direction.
  • one embodiment of me invention encompasses a me od of making microtiter plates comprising the steps of (i) incorporating a photobleachable dye into a material so as to render ie material essentially opaque, (ii) forming the essentially opaque material into a microtiter plate having a plurality of wells formed therein, each of d e wells having a bottom formed from a portion of the essentially opaque material, and (iii) irradiating d e bottoms of the wells so as to render the material forming die bottoms transparent.
  • d e mediod of making microtiter plates comprises die steps of (i) forming a plate having a plurality of wells from an essentially transparent material, each of the wells having a bottom and a sidewall, and (ii) i ⁇ adiating the sidewalls widi a beam of light so as to render die sidewalls essentially opaque.
  • Figure 1 is plan view of a microtiter plate according to die current invention.
  • Figure 2 is a detailed view of die portion of Figure 1 enclosed by die circle indicated by II.
  • Figure 3 is a cross section taken through line III-III shown in Figure 2.
  • Figure 4 is a detailed plan view of one of die microwells shown in Figured. '
  • Figure 5 is a detailed view of die portion of Figure 3 enclosed by die circle indicated by V, showing an enlargement of the boundary between microwells.
  • Figure 6 is a view showing a further enlargement of the microwell boundary shown in Figure 5.
  • Figures 7(a) and (b) are cross sectional views showing two alternate embodiments of die microwells according to die current invention.
  • Figure 8 is a plan view of an alternate arrangement of microwells according to die current invention. In order to avoid confusion due to unnecessary 8 complexity of the drawing, the bottom is shown in only one of the microwells shown in Figure 8.
  • Figure 9 is a cross section taken along line IX-IX shown in Figure 8.
  • Figure 10 is a cross section taken along line X-X shown in Figure 8.
  • Figure 11 is a plan view of another alternate arrangement of microwells according to the current invention.
  • Figure 12 is a cross section taken along line XII-XII shown in Figure 11.
  • a microtiter plate 1 according to die current invention is shown in Figure 1.
  • the microtiter plate 1 is preferably rectangular, being , approximately 125 mm long, 85 mm wide, and 4 mm thick. Use of these dimensions allows the plate to be handled and indexed by currently available devices for automated microtiter plate handling.
  • the microtiter plate 1 according to die current invention may contain a very large number of very small microwells 2.
  • each of the microwells 2 has a depdi of approximately 1 mm and a volume of approximately 0.5 microliters or less.
  • 9600 microwells, each having a volume of approximately 0.4 microliters are arranged in 120 rows and 80 columns.
  • Each of die microwells 2 has an inlet 6 that forms an approximately 1 mm square. However, a lesser number of larger microwells, for example 2400 microwells, each having a depdi of approximately 3 mm and a volume of approximately 5 microliters, arranged in 60 rows and 40 columns, may also be preferred. In this embodiment, each microwell has an inlet mat forms an approximately 2 mm square. Aldiough a rectangular microtiter plate 1 is shown, it should be understood diat die microtiter plate according to die current invention could be fashioned in other shapes as well, for example a circular plate having a 125 mm diameter containing 14,500 wells arranged in a honeycomb pattern could be constructed. Such a circular arrangement will maximize the use of a circular imagining field.
  • d e microtiter plate 1 has a border 4 diat surrounds a working portion 3 of the plate.
  • the working 9 po ⁇ ion 3 of the plate 1 consists of microwells 2 having square inlets 6 formed on die upper surface 6 of die plate.
  • die body of each microwell 2 is formed by four walls, each of which extends downward from the inlet 6.
  • the four walls consist of a first pair of opposing walls 10 and 12 and a second pair of opposing walls 11 and 13.
  • the walls 10-13 are inclined at an angle A to die vertical direction - diat is, an angle with respect to a line perpendicular to d e plane of the plate ⁇ as shown best in Figure 5.
  • the microwells 2 have ie sliape of an inverted four sided pyramid.
  • the walls 10-13 are steep, so d at me angle A is no greater than approximately 45°.
  • die angle A is approximately 30° or less.
  • die bottoms 14 of die microwells 2 are preferably flat. However, other shape bottoms, such as arcuate or conical bottoms, could also be utilized.
  • die walls 11 and 13 of adjacent microwells 2 intersect along edges 16, as shown best in Figures 3 .and 4.
  • the walls 10 and 12 of adjacent microwells 2 intersect along edges 18.
  • edges 16 and 18 form the inlets 6 of the microwells 2.
  • die boundary between die inlets 6 of adjacent microwells 2 is formed entirely by edges 16 and 18 so as to avoid die formation of flat, horizontal surfaces that would allow liquid to collect between microwells.
  • the microwells have the sliape of four side pyramids, odier sliapes could also be utilized provided diat die boundary between the inlet of adjacent microwells is formed by an edge without any intervening flat, horizontal surfaces diat would allow liquid to collect.
  • microwells could be formed with walls having a first portion 40, adjacent die inlet edge, diat is inclined or conical, and a second portion 42, adjacent die well bottom, d at is vertical or cylindrical.
  • die depdi of die vertical portion of the walls die depdi of the microwell 40 10 and, therefore, its volume, can be increased wi iout increasing the size of its inlet.
  • this geometry allows increasing the volume of die microwells without reducing dieir density.
  • Aldiough the walls in Figures 3 and 7 are shown as being straight, arcuate walls, having eiuier convex or concave curvature, could also be utilized, provided diat diey formed sufficiently sharp edges, as discussed below. As shown in
  • microwells 43 with arcuate bottoms 44 could also be formed.
  • Figures 8-10 show an alternate embodiment in which me microtiter plate 1 ' has hexagonal microwells 32 arranged in a honeycomb configuration.
  • die microwells 32 have six inclined walls 20-25 that intersect with the walls of die adjacent microwells along edges 25-30.
  • Figures 11 and 12 show yet anodier embodiment in which conical microwells 40 are utilized.
  • me inlets of the microwells .are circles and die bottoms come to a point.
  • flat or arcuate bottoms as previously discussed, could also be utilized.
  • the included angle B of die cone is preferably no greater ttian approximately 90°, and, more preferably, no greater than approximately 60°.
  • diree faceted projections 43 are formed between each diree adjacent microwells, with each facet facing one of die microwells.
  • the projections 43 form points mat are connected by edges 42, diereby ensuring ⁇ iat liquid cannot collect between microwells 40.
  • edges 16 and 18 in die embodiment shown in Figures 1-4, in as sharp a manner as possible, it must be realized diat it is impossible to form a perfect edge in any material. This is especially so with respect to the plastics from which the microtiter plates 1 according to the current invention are preferably formed, as discussed further below.
  • the edges 16 and 18 will typically appear rounded, as shown in Figures 5 and 6, ra ⁇ ier than perfectly sharp.
  • die edges 16 and 18 have a width W (diat is, the widdi of die rounded portion connecting the walls 11 and 13 and 10 and 12) no 11 greater than approximately 250 microns and a radius of curvature R no greater than approximately 150 microns.
  • the widdi F of any flat, horizontal surfaces on the edges 16 and 18 should preferably be less than approximately 80 microns.
  • Microwells constructed according to die current invention ensure that all of the liquid deposited on d e worl ing portion 3 will find its way into one of die microwells since there are no flat surfaces between microwells that would allow liquid to collect and the edges 16 and 18 and die walls 10-13 tend to divert any liquid dispensed between microwells toward die well cavity. Thus, extremely accurate positioning of a dispensing orifice to dead center of the microwells is unnecessary, thereby permitting the use of a large number of very small microwells 2.
  • die wells can be filled widi liquid much die same way that paint is applied to a wall widi a sprayer.
  • die beads which are randomly distributed over the worlcing surface of die plate, are dien allowed to settle.
  • die geometry of the well inlets ensures diat each of die beads rolls into one of die wells. Consequently, if 20,000 beads are applied to the surface of die plate, each well will 12 contain on average two beads as defined by a Poisson distribution.
  • the edianol is then removed via evaporation and a small amount of compound is cleaved from the beads.
  • the target usually an enzyme or protein receptor, to be tested is dien applied to die surface of the plate using die inkjet printer head technology described above.
  • Microtiter plates according to die current invention are preferably formed by injection molding a plastic.
  • Suitable injection molders include Atlantis Industries, Inc., Federal and Park, Milton, Delaware.
  • any one of a large number of plastics such a polypropolyene, nylon, or polystyrene could be utilized. While such plastics are suitable for radiochemical or spectrophotometric assays, their intrinsic fluorescence causes problems in fluorescence detection, as previously discussed.
  • this problem is solved by forming die microtiter plate 1 from a liquid crystal polymer, which has essentially no fluorescence with respect to wave lenguis in the 300 nm to 650 nm range, which is the range of interest for most biological screening applications.
  • die term "essentially no fluorescence" refers to materials whose fluorescence cannot be detected using a CCD camera.
  • pigments are added to die liquid crystal polymer so as to obtain an opaque black material, thereby minimizing reflectance.
  • the use of an intrinsically non-fluorescent and non-reflective liquid crystal polymer minimizes interference from the microtiter plate material in fluorescent measurement applications.
  • liquid crystal polymers mold uniformly and are very chemically resistant.
  • Suitable liquid crystal polymers include, but are not limited to, glass reinforced and mineral filled polymers, such as ose available from Hoechst Celanese, including, but not limited to grades A115, A130, A150, A230, A410, A420, A422, A430, A435, A440, A515, A530, A540, A625, A700, B230, C115, C130, C150, C550, C810, E130i, K130, K140,
  • die liquid crystal polymer is grade A530D.
  • die microtiter plate is formed from a highly reflective material, such as white polystyrene, polycarbonate, or acrylic, so as to enhance die performance of the microtiter plate when used for measurement of luminescence.
  • a highly reflective material such as white polystyrene, polycarbonate, or acrylic
  • sufficient reflectance is obtained by adding pigments, such as zinc or tungsten oxide, to die material forming the microtiter plate so as to yield, for example, a white 13 opaque material.
  • the walls and bottoms of die microwells could be coated widi a reflective film by vapor deposition of metal particles, direct spraying, or lamination under vacuum of mirrored MylarTM film.
  • Spectrophotometric assays require that die bottom of die well be optically clear. Consequently, in still ano ier embodiment, suitable for use in such assays, the bottoms of d e microwells are transparent, while die walls are non- reflective, as previously discussed.
  • This embodiment may be formed by incorporating a photobleachable dye into a liquid crystal polymer, thereby resulting in material having an opacity greater than approximately 2 absorbance units (1 % transmittance), and preferably greater than approximately 3 absorbance units (0.1 % transmittance).
  • Suitable photobleachable dyes include methyl violgens, paraquat, and nitrophenol based dyes, which are added in sufficient quantity to achieve die specified opacity singly or in combination.
  • die microwell bottoms are irradiated with a fine, intense laser light of proper wave length, preferably of several millivolts in a 0.5 mm widdi, diereby bleaching die materi ⁇ d iat forms the bottoms of the wells so as to result in transparent bottoms of preferably less than approximately 0.01 absorbance units (99.95 % transmittance) and, more preferably, less man approximately 0.001 absorbance units (99.99 % transmittance).
  • Such bottoms facilitate the transmission of light through the microwell, while die dye in die material forming the walls of the wells prevents die piping of light wid ⁇ n die plate material between adjacent wells, thereby avoiding undesirable "cross-talk.” Consequently, the accuracy of spectrophotometric measurements is enhanced.
  • this embodiment could be formed by injection molding die microtiter plate from a clear material, such as polystrene or a liquid crystal polymer, and uien bonding a photochromic film, such as DuPont DyluxTM, onto the side walls of die microwells using heat lamination (shrink wrap), chemisorption, or an adhesive.
  • a clear material such as polystrene or a liquid crystal polymer
  • a photochromic film such as DuPont DyluxTM
  • die microtiter plate from a clear material, such as polycarbonate, polystrene, or acrylic, diat lias been doped widi photochromic dyes or films but then render die walls of die wells opaque by application of high intensity light to only the walls, for example by irradiating die wall material with near ultraviolet light from 300-400 nm for several minutes to hours, as necessary to achieve die desired opacity.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
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  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Optical Measuring Cells (AREA)

Abstract

Dispositif servant à contenir un liquide, tel qu'une plaque de microtitration, et présentant une pluralité d'alvéoles. Chacune de ces alvéoles possède des parois latérales venant en intersection dans un bord définissant la limite entre des alvéoles contiguës. Ce bord limitrophe empêche le liquide de se déposer entre les alvéoles, ce qui provoquerait la pénétration dans une des alvéoles de la totalité du liquide appliqué à la plaque. Cette plaque de microtitration peut être fabriquée en un matériau présentant une réflectance et/ou une fluorescence optimisées en fonction de l'utilisation déterminée de la plaque de microtitration. Les plaques de microtitration mises en application afin de mesurer la fluorescence sont fabriquées en un matériau possédant une fluorescence limitée, tel qu'un polymère de cristaux liquides, tandis que les plaques de microtitration utilisées pour des mesures de luminescence sont fabriquées en un matériau possédant une réflectance élevée. Les plaques de microtitration conçues pour des analyses spectrophotométriques comportent des alvéoles possédant des fonds transparents et des parois opaques. On peut fabriquer ces alvéoles à fond clair par incorporation d'un colorant pouvant être décoloré à la lumière dans le matériau de la plaque, de manière à opacifier ce matériau, puis par irradiation des fonds des alvéoles, de façon à les rendre transparentes. La création de ces alvéoles peut également consister à fabriquer la plaque avec un matériau transparent, puis à irradier les parois latérales au moyen d'un faisceau de lumière afin de les opacifier.
PCT/US1998/006368 1998-04-01 1998-04-01 Dispositif sous forme de plaque servant a contenir de petits volumes de liquide WO1999049974A1 (fr)

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Application Number Priority Date Filing Date Title
PCT/US1998/006368 WO1999049974A1 (fr) 1998-04-01 1998-04-01 Dispositif sous forme de plaque servant a contenir de petits volumes de liquide
AU67911/98A AU6791198A (en) 1998-04-01 1998-04-01 Plate apparatus for holding small volumes of liquids

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PCT/US1998/006368 WO1999049974A1 (fr) 1998-04-01 1998-04-01 Dispositif sous forme de plaque servant a contenir de petits volumes de liquide

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001003833A1 (fr) * 1999-07-13 2001-01-18 Commissariat A L'energie Atomique Support d'analyse a transmission de lumiere de fluorescence
WO2001052988A1 (fr) * 2000-01-21 2001-07-26 Greiner Labortechnik Gmbh Contenant pour stocker une matiere biologique
GB2370112A (en) * 2000-12-15 2002-06-19 Hybaid Ltd Multiwell sample plates
WO2004025277A1 (fr) * 2002-09-13 2004-03-25 Kibron Inc. Oy Procede de mesure de la tension superficielle
GB2396912A (en) * 2002-12-10 2004-07-07 Nippon Sheet Glass Co Ltd Biochemical vessel
EP2339632B1 (fr) * 2009-12-28 2014-03-12 Sony Corporation Capteur d'images et son procédé de fabrication, et dispositif de capteur
CN109701671A (zh) * 2018-12-27 2019-05-03 复旦大学 一种微液滴阵列芯片及其制造和使用方法
WO2020201147A1 (fr) * 2019-03-29 2020-10-08 Phase Holographic Imaging Phi Ab Microplaque pour microscopie

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EP0106662A2 (fr) * 1982-10-12 1984-04-25 Dynatech Laboratories, Incorporated Récipients non-fluorescents pour contenir des échantillons dans un test par fluorescence
WO1994021379A1 (fr) * 1993-03-16 1994-09-29 Westaim Technologies Inc. Plaque de microtitrage perfectionnee et immunodosages menes a bien dans celle-ci
DE4405375A1 (de) * 1994-02-19 1995-08-24 Fritz Nerbe Nachfolger Juergen Mikrotiterplatte
DE4424112A1 (de) * 1994-07-08 1996-01-11 Raytest Isotopenmesgeraete Gmb Verfahren zur Herstellung eines Probenträgers
WO1996036436A1 (fr) * 1995-04-25 1996-11-21 Irori Matrices programmables a distance et dotees de memoires, et leur utilisation
EP0816827A2 (fr) * 1996-06-24 1998-01-07 Schweizerische Eidgenossenschaft vertreten durch das AC-Laboratorium Spiez der Gruppe für Rüstungsdienste Assemblage à cavités multiples pour l'analyse instrumentale
WO1998028075A1 (fr) * 1996-12-20 1998-07-02 Imaging Research Inc. Plaque a micro-puits pour imagerie d'essais en fluorescence, chimiluminescence, bioluminescence et colorimetrie

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0106662A2 (fr) * 1982-10-12 1984-04-25 Dynatech Laboratories, Incorporated Récipients non-fluorescents pour contenir des échantillons dans un test par fluorescence
WO1994021379A1 (fr) * 1993-03-16 1994-09-29 Westaim Technologies Inc. Plaque de microtitrage perfectionnee et immunodosages menes a bien dans celle-ci
DE4405375A1 (de) * 1994-02-19 1995-08-24 Fritz Nerbe Nachfolger Juergen Mikrotiterplatte
DE4424112A1 (de) * 1994-07-08 1996-01-11 Raytest Isotopenmesgeraete Gmb Verfahren zur Herstellung eines Probenträgers
WO1996036436A1 (fr) * 1995-04-25 1996-11-21 Irori Matrices programmables a distance et dotees de memoires, et leur utilisation
EP0816827A2 (fr) * 1996-06-24 1998-01-07 Schweizerische Eidgenossenschaft vertreten durch das AC-Laboratorium Spiez der Gruppe für Rüstungsdienste Assemblage à cavités multiples pour l'analyse instrumentale
WO1998028075A1 (fr) * 1996-12-20 1998-07-02 Imaging Research Inc. Plaque a micro-puits pour imagerie d'essais en fluorescence, chimiluminescence, bioluminescence et colorimetrie

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001003833A1 (fr) * 1999-07-13 2001-01-18 Commissariat A L'energie Atomique Support d'analyse a transmission de lumiere de fluorescence
FR2797053A1 (fr) * 1999-07-13 2001-02-02 Commissariat Energie Atomique Support d'analyse a transmission de lumiere de fluorescence
WO2001052988A1 (fr) * 2000-01-21 2001-07-26 Greiner Labortechnik Gmbh Contenant pour stocker une matiere biologique
GB2370112A (en) * 2000-12-15 2002-06-19 Hybaid Ltd Multiwell sample plates
WO2004025277A1 (fr) * 2002-09-13 2004-03-25 Kibron Inc. Oy Procede de mesure de la tension superficielle
US7281416B2 (en) 2002-09-13 2007-10-16 Kibron Inc. Oy Method for surface tension measurement
GB2396912A (en) * 2002-12-10 2004-07-07 Nippon Sheet Glass Co Ltd Biochemical vessel
GB2396912B (en) * 2002-12-10 2006-09-06 Nippon Sheet Glass Co Ltd Biochemical vessel
EP2339632B1 (fr) * 2009-12-28 2014-03-12 Sony Corporation Capteur d'images et son procédé de fabrication, et dispositif de capteur
CN109701671A (zh) * 2018-12-27 2019-05-03 复旦大学 一种微液滴阵列芯片及其制造和使用方法
WO2020201147A1 (fr) * 2019-03-29 2020-10-08 Phase Holographic Imaging Phi Ab Microplaque pour microscopie
CN113924164A (zh) * 2019-03-29 2022-01-11 相位全息成像Phi有限公司 用于显微镜检查的微板

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