WO2001060519A1

WO2001060519A1 - Well plate holder

Info

Publication number: WO2001060519A1
Application number: PCT/US2001/040110
Authority: WO
Inventors: Rene Bongard; George Tokiwa; Kathryn E. Rayca; Thomas Sabol; James Petersen
Original assignee: Orchid Biosciences, Inc.
Priority date: 2000-02-14
Filing date: 2001-02-14
Publication date: 2001-08-23
Also published as: AU2001247971A1; WO2001060519B1

Abstract

A well plate holder (10) has a generally planar bottom portion (24) having a first side, a second side, a third side and a fourth side. The first side has a first side wall portion (26) extending therefrom and the second side having a second side wall portion (26) extending therefrom. The third side may have a third side wall and the fourth side has a fourth side wall portion (26) extending therefrom. The first side wall may comprise dowel pins (28) and the second side wall may comprise a holding pin (30).

Description

WELL PLATE HOLDER

Technical Field

The present invention relates generally to a device holder used to manipulate a device during automated processing of the device, and rore particularly, to a well plate holder particularly suited for robotic manipulation during processing.

Background Of The Invention

Methods of making a homologous series of compounds, or the testing of new potential αrug compounds comprising a series of light compounds, nas been a slow process because each member of a series or each potential drug must be made individually and tested individually. For example, a plurality of potential drug compounds that differ perhaps only by a single ammo acid or nucleotide base, or a different sequence of ammo acids or nucleotides are tested by an agent to determine their potential for being suitable drug candidates. These steps are typically performed manually which is both expensive and time consuming.

These processes require various stages of processing such as reagent mixing and thermal cycling. These processes may be carried out using a microtiter plate in which a number of wells may be used to carry out simultaneous processing. One size microtiter plate has 384 reagent wells in an area about 5 inches x 3.3 inches. Of course, various numoers of wells may DΘ contained

plates. For example, 1536 wells on a similar size plate may be used. Microtiter places are most commonly formed of plastic material so they are lightweight and inexpensive. Methods for automating these processes include automated reagent loading, testing and manipulating such as thermal cycling.

Commonly known polymerase chain reaction

(PCR) processes use a number of thermal cycles followed by cool down periods. Because the microtiter plates are made from plastic, the microtiter plates are subject to warpage . Warpage makes the plate difficult to manipulate, difficult to aspirate the fluid therein and difficult to dispense the fluid therefrom.

Because the microtiter plates are commonly formed of plastic material and have a low profile with an irregular cross section, a robotic manipulator may not easily or reliably grip the microtiter plate.

It would therefore be desirable to allow the well plate to be easily manipulated and to compensate any distortion of the well plate caused by thermocyclmg . Summary Of The Invention

It is therefore one object of the invention to provide improved robotic manipulation of a well plate .

In one aspect of the invention, a well plate holder has a generally planar bottom portion having a first side, a second side, a third side and a fourth side. The first side has a first side wall extending therefrom and the second side has a second side wall extending therefrom. The third and fourth sides also haλ-'e a respective side wall. The side walls are sized so that a robotic manipulator may easily grasp them to hold and manipulate the holder and the well plate therein.

One feature of the invention is that said first side wall may comprise dowel pms and the second side wall may comprise a holding pin.

In a further aspect of the invention, an analysis system has a robot having a robotic manipulator. A plate holder is sized to receive a well plate and has a generally planar bottom portion. The bottom portion has four sides with respective side walls extending therefrom. The first and second side walls have respective dowel pms and holding pms for retaining the plate to the plate holder. Each side wall is sized to be gripped by the fingers of the robotic manipulator. One advantage of the invention is tnat cr.e well plate nolder may oe configured so tnat tne automated processing equipment may read a bar code on an edge of the well plate Another advantage of the invention is that the well plate may be easily placed within the well holder witnout the use of specialized tools .

Other objects and features of the present invention will become apparent when viewed light of the detailed description of the preferred embodiment when taken m conjunction with the attached drawings and appended claims.

Brief Description Of The Drawings

Fig. 1 is a top view of a well plate holder according to the present invention having a well plate disposed therein.

Fig. 2 is a perspective end view of the well holder and well plate assembly of Fig. 1.

Fig. 3 is a perspective view of an automated processing system according to the present invention.

Fig. 4 is an enlarged perspective view of the robotic manipulator of Fig. 3 gripping the well plate assembly.

Fig. 5 is a perspective view of the robotic manipulator gripping the well plate holder a different position than Fig. 4. Fig. 6 is a perspective view of a first embodiment of a well plate holder.

Fig. 7 is a side view of a dowel pin.

Fig. 8 is a side view of a second pin.

Fig. 9 is a perspective view of a second embodiment of a well plate holder.

Fig. 10 is a top view of a well plate holder according to a third embodiment of tne invention .

Fig. 11 is an elevational view of an end bar of Fig. 10.

Fig. 12 is a perspective view of a fourth embodiment of a well plate according to the present invention.

Fig. 13 is a fifth embodiment of a well plate holder according to the present invention.

Detailed Description of the Preferred Embodiment

In the following figures, the same reference numerals will be used to identify identical components. The present invention is described with respect to a well plate. The well plate is defined as a microtiter plate, PCR plate or other plates having a plurality of wells therein. The plate may also comprise a multilayer microfluidic plate. Referring now to Fig. 1, a well plate/well plate holder assembly 10 is illustrated having a well plate 12 and a well plate holder 14. Well plate holder 14 is sized to receive and hold well plate 12 therein. Well plate 12 has a plurality of wells 16 arranged in rows and columns. As shown, 384 wells are arranged in 16 rows and 24 columns. Of course, the number of wells may vary depending on the process to be carried out. The filling of wells 16 may be automated as part of the process. Well plate 12 is preferably formed of a plastic material. The plastic material is preferred due to its light weight. However, the plastic material has a tendency to become distorted or warped during thermal cycling. The present invention is used to reduce warpage the plate.

Well plate 12 has a ridge 18 that extends around the perimeter. Ridge 18 does not extend the same distance from well plate holder 14 as does a top surface 20. That is, the ridge 18 has a thickness less than well plate. Well plate 12 has a plurality of receiving holes 22 formed therein. Commonly, receiving holes 22 are located two on each edge.

Well plate holder 14 has a generally planar bottom portion or base 24 with a plurality of side walls 26 extending therefrom. Preferably, side walls 26 extend in a perpendicular direction from the plane of base 24. The side walls extend a distance above base 24 a distance to allow manual gripping as well as by a robotic manipulator as will be further described below. At least one side wall 26 nas dowel pms 28 that extend into receiving holes 22. One sidewall 26 has nold g p s 30. Holding pms 30 are used to hold ridge 18 and therefore the well plate 12 to base 24 of well plate holder 14. If a ridge 18 is not present on well plate 12, holding pms 30 may be positioned to hold top surface 20 against base 24.

Referring now to Fig. 2, well plate 12 has a bar code 34 positioned on one side thereof. Bar code 34 is used by the automated equipment to identify the particular well plate 12 and the reagent therein. One sidewall 26 preferably has a bar code opening 36 to allow a bar code reader in the automated equipment to read bar code 34. Bar code 34 is preferably located on a lateral side of well plate 12.

Referring now to Fig. 3, a perspective view of an automated processing system 40 is illustrated. Automated processing system has a robot 42 with an arm 44 and a robotic manipulator 46. Robotic manipulator 46 nas gripping fingers 48 that extend therefrom and are used to grip side wall 26 of well plate holder 14. Fingers 48 grip the side walls 26 of well plate holder 14 to manipulate well plate/well plate holder assembly 10. The side walls 26 are sized so that well plate holder 14 is securely held during manipula ion. For example, robot 42 may be used to position assembly 10 within a rack 50 or m a bar code reader 52. Rack 50 may be a multilevel thermal cycling rack. Referring now to Fig. 4, as illustrated, fingers 48 are gripping lateral side walls 26 so tnat Oar code 34 is still visiole within bar code opening 36.

Referring now to Fig. 5, robotic manipulator 46 is illustrated with fingers 48 gripping longitudinal walls 26. Gripping either longitudinal walls or lateral walls may be desirable at various stages of processing.

Referring now to Fig. 6, a first embodiment

60 of a well plate holder 14 is illustrated. Well plate holder 14 is preferably formed of a light weight and rigid material such as aluminum. In one constructed embodiment, 2024 aluminum having a 0.08 inch thickness was used to construct well plate holder 14. Both side wall and base 24 are preferably constructed from the same material although different materials may be used. In this embodiment, side wall 26 are integrally formed with based 24. The first lateral sidewall 26 has bar code opening 36 and dowel holes 62. The first lateral side wall 26 may be mushroom-shaped. That is, dowel holes 62 may be mounted on laterally extending radially shape portions 61 that extend from a base portion 63. The width of portion 61 is thus greater than the width of base portion 63.

A second lateral sidewall 64 is positioned opposite lateral sidewall 26. Lateral sidewall 64 m tnis embodiment is comprised of three disparate portions; a pair of holding walls 66 and a center wall 68. Center wall 68 is positioned bet-veen tne noldmg p walls 66 Preferably, holding pm walls 66 and center wall 68 are separated by a space. A robotic manipulator may be used to grip holding walls 66 and center wall 68. A pair of finger slots 70 are formed m base 24 between respective holding pm wall 66 and center wall 68. Finger slots 70 increase tne manual maneuverability of well plate holder 14.

Base 24 preferably has a plurality of cutouts 72. As illustrated, six cutouts are formed m base 24. Cutouts 72 are illustrated as oval shaped. However, various shapes and numbers of cutouts 72 may be formed. Cutouts 72 are used to reduce the weight of the well plate. The existence, the size and shape of the cutouts may vary as would be evident to those skilled in the art.

Holding pm wall 66 has holding pm hole 74 positioned therein. Holding pms 30 are preferaoly press fit into holding pm hole 74. Of course, holding pms may be coupled to side wall 26 m a variety of ways including securing with a fastener or adhesive or integrally forming them therewith.

Referring now to Fig. 7, a dowel pm 28 that is to be received within dowel holes 62 of Fig. 6 is illustrated. Dowel pm 28 has an end portion 76 sized to be received within dowel hole 62. Dowel p 28 has a body portion 78 having an insertion end 80 that is tapered to assist m tne insertion of dowel pm 28 within receiving holes 22 of well plate In the constructed embodiment, dowel pms 28 were formed of stainless steel .

Referring now to Fig. 8, a holding p 30 is illustrated. Holding p 30 has a diameter to be received within holding pm hole 74 as shown m Fig. 6. Holding p 30 has a body 82 with an axially extending wall 84 and a rounded end 86. Axially extending wall 84 is used to position ridge 18 of well plate 12 between it and base 24. Rounded end 86 is provided to reduce the sharp edge and prevent damage to well plate 12. In the constructed embodiment, holding pms 30 were formed of stainless steel.

Referring now to Fig. 9, a second embodiment 60' of a well plate holder is illustrated. The well plate holder is similar in every aspect with that illustrated m Fig. 6 except that one cutout 72' is provided rather than a plurality of cutouts. Cutout 72' has a rectangular shape. In this manner, well plate holder 14 ' has a reduced weight from that shown in Fig. 6.

Referring now to Figs. 10 and 11, a third embodiment 60 is shown. The third embodiment 60 is similar m every respect to that illustrated m Fig. 6, including lateral wall 64 and longitudinal side wall 26. However, one lateral wall 26 is illustrated as a separate component. Sidewall 26 9

preferably has a similar shape as that shown in Fig 6 except that two fastener holes 88 are provided therethrough. Fastener holes 88 align with fastener channels 90 formed m base 24. Fastener holes 88 and fastener channels 90 eacn receive a fastener 92 to secure lateral wall 26 to base 24.

Referring now to Fig. 12, a fourth embodiment 60''' is illustrated. Fourth embodiment 60 ' ' * has a well plate holder 14 similar to that shown in Fig. 6 above except lateral walls are formed differently. In lateral wall 94, a bar code opening 36 has not been provided. Lateral wall 96 is formed of a single wall positioned between finger slots 70 ' ' . Lateral wall 96 has holding p holes 74 positioned therein similar to that shown above.

Referring now to Fig. 13, a fifth embodiment 60 ' ' ' ' is illustrated. Fifth embodiment 60 ' ' ' is similar to that illustrated in Fig. 9 m that a single cutout opening 72 ' positioned within based 24. In this embodiment, however, lateral walls 98 are formed of a pair of extensions 100. Extensions 100 do not have a holding pm hole 74 or dowel hole 62 as shown above. In this manner, no downward force is provided to hold a well plate within well plate holder 14. The fifth embodiment is suitable for use prior to thermal cycling performed on the well plates.

In operation, well plates 12 are typically provided preloaded with reagents. A microseal film is formed across the top surface 20 of well plate 12 Well plates 12 are manually inserted into well plate holder 14 Preferably, the liquids within the wells do not contact the film seal during insertion Preferably, the well plate 12 is positioned within well plate holder 14 at about a 20 degree angle so that the dowel pms 28 align with receiving holes 22 The well plate 12 and well plate holder 14 may be placed m a centrifuge to spin down the liquids m the wells. The finger slots 70 may be used to grip the well plate holder 14 while the well plate 12 is pushed under holding pins 30. Preferably, each holding pm 30 is positioned on well plate m turn Holding pms 30 and dowel pins 28 mitigate the effects of warping during thermal cycling as well as said well plate 12 during manipulation. That is, the well plate holder can hold the well plate m straightened position if warping has occurred. Well plate holder may also prevent warping from occurring Both pairs of side wall 26 allow the well plate holder 14 to be gripped during robotic manipulation

The well plate 12 and well plate holder 14 may be used together with a variety of processing devices such as a bar code reader/regπp station, a carousel or multimeter.

While particular embodiments of the invention have been shown and described, numerous variations and alternate embodiments will occur to those skilled in the art. Accordingly, it is intended that the invention be limited only m terms of the appended claims

Claims

What Is Claimed is: 1. A holder for holding a well plate comprising: a generally planar bottom portion; said bottom portion having a first side, a second side, a third side and a fourth side; said first side having a first side wall portion extending therefrom; and said second side positioned opposite said first side wall, said second side having a second wall portion extending therefrom; said third side having a third side wall; and said fourth side having a fourth side wall position opposite said third side wall.

2. A holder as recited m claim 1 wherein said first side wall, said second side wall, said third side wall and said fourth side wall are integrally formed with said base plate.

3. A holder as recited m claim 1 wherein said first side wall is a separately attached component .

4. A holder as recited m claim 1 wherein said first side wall comprises dowel pms.

5. A holder as recited in claim 1 wherein said second side wall comprises a holding pm.

6. A holder as recited claim 1 therein said bottom portion comprises a fmger slot.

7. A holder as recited m claim 1 wherein said second side wall comprises a center wall positioned between a pair of holding pm walls.

8. A holder as recited m claim 7 wherein said bottom portion comprises a pair of fmger slots, one fmger slot between one of said pair of holding pm wall and said center and the other one of said pair of holding pms walls and said center wall.

9. A holder as recited m claim 1 wherein said first side wall has a bar code opening therethrough.

10. A holder as recited in claim 1 wherein said bottom portion has a cutout therethrough.

11. A holder as recited m claim 1 wherein said bottom portion has a plurality of cutouts therethrough.

12. A holder as recited in claim 1 wherein said first side wall and said second side wall comprise a pair of extensions.

13. A plate holder comprising: a generally planar bottom portion; said bottom portion having a first side, a second side, a third side and a fourth side, said first side having a first side wall having dowel pms extending therefrom and said second side //all positioned opposite said first side wall having holding pms extending therefrom, said third side having a third side wall and said fourth side navmg a fourth side wall extending therefrom.

14. A holder as recited in claim 13 wherein said bottom portion comprises a fmger slot.

15. A holder as recited m claim 13 wherein said second side wall comprises a center wall positioned between a pair of holding pm walls.

16. A holder as recited in claim 15 wherein said bottom portion comprises a pair of fmger slots, one fmger slot between one of said pair of holding pm wall and said center and the other one of said pair of holding pins walls and said center wall.

17. A holder as recited in claim 13 wherein said first side wall has a bar code opening therethrough.

18. A well plate holder for use with a robotic manipulator having fingers, said well plate holder comprising: a generally planar bottom portion; said bottom portion having a first side, a second side, a third side and a fourth side, said first side having a first side wall having dowel pms extending therefrom and said second side wall positioned opposite said first side wall having holding pms extending therefrom. , said third side having a third side wall and said fourth side having a fourth side wall, said first sidewall, said second side wall, said third side wall and said fourth side wall sized to be gripped by said robotic manipulator.

19. A holder as recited in claim 18 wherein said bottom portion comprises a finger slot.

20. A holder as recited in claim 18 wherein said second side wall comprises a center wall positioned between a pair of holding pin walls.

21. A holder as recited in claim 20 wherein said bottom portion comprises a pair of finger slots, one finger slot between one of said pair of holding pin wall and said center and the other one of said pair of holding pins walls and said center wall.

22. A holder as recited in claim 8 wherein said first side has a bar code opening therethrough.

23. A analysis system comprising: a robot having a robotic manipulator with movable fingers; a plate; a plate holder sized to receive said plate, said plate holder a generally planar bottom portion; said bottom portion having a first side, a second side, a third side and a fourth side, said first side having dowel pins extending therefrom and said third side opposite said first side having holding pms extending therefrom, said first sice, said second side said third side and said fourtn sized to be gripped by said fingers.

24. An analysis system as recited m claim 23 wherein said bottom portion comprises a fmger slot.

25. An analysis system as recited m claim 23 wherein said second side wall comprises a center wall positioned between a pair of holding pm walls.

26. An analysis system as recited m claim 25 wherein said bottom portion comprises a pair of fmger slots, one fmger slot between one of said pair of holding pm wall and said center and the other one of said pair of holding pms walls and said center wall .

27. An analysis system holder as recited in claim 23 wherein said first side has a bar code opening therethrough.