EP1214139A2 - High throughput screening card - Google Patents

High throughput screening card

Info

Publication number
EP1214139A2
EP1214139A2 EP00965123A EP00965123A EP1214139A2 EP 1214139 A2 EP1214139 A2 EP 1214139A2 EP 00965123 A EP00965123 A EP 00965123A EP 00965123 A EP00965123 A EP 00965123A EP 1214139 A2 EP1214139 A2 EP 1214139A2
Authority
EP
European Patent Office
Prior art keywords
support
well
membrane
membrane filter
wells
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.)
Ceased
Application number
EP00965123A
Other languages
German (de)
French (fr)
Inventor
Brian Foley
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.)
EMD Millipore Corp
Original Assignee
Millipore Corp
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 Millipore Corp filed Critical Millipore Corp
Publication of EP1214139A2 publication Critical patent/EP1214139A2/en
Ceased legal-status Critical Current

Links

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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B01L3/50255—Multi-well filtration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B01D61/18—Apparatus therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B01J2219/00317—Microwell devices, i.e. having large numbers of wells
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries

Definitions

  • the Multiscreen® multiple well membrane filter for laboratory and research use is used for laboratory assays.
  • These filters and its competitive products are made by first creating a support plate by injection molding a resin.
  • a resin typically, polyethylene, BarexTM polymer, acrylic or styrene is used as the resin.
  • the support plate would have a number of through holes, with the wall of such holes serving as the side wall (circular well) or walls (multi-hedral well) of the wells.
  • the resin in its injection-molded form must not interfere with the laboratory assay it is used for.
  • the multi-well device is then created by cutting filter membrane into discs and attaching the discs to one side of each through hole, thereby creating the wells.
  • Such filter membrane is typically attached to the support by bonding, either thermal or ultrasonic. This is a labor-intensive operation, adding substantially to the cost of manufacturing.
  • a mold has to be produced for each device.
  • the process of producing a mold for use in production first requires the production of a prototype mold. Such molds cost around $50,000. Once the final design of the product is agreed upon, a production mold is made.
  • the cost of a production mold varies with the number of cavities intended for the injection-molding tool. For example, a one-cavity tool for 96 well plate production requires a mold that typically costs $90,000. A two-cavity tool for 96 well plate production requires a mold that typically costs $160,000.
  • a limitation of the molds is that they are suitable only for similar materials. One could not use the polyethylene mold to produce a styrene support. This limits the products that can be made available because it is not cost effective to produce the same plate design from two different materials due to the cost of capital and the time to recoup the investment.
  • PTFE Teflon® polytetraflouroethylene
  • a substantially inert material is not used to produce supports because it is not a cost effective alternative for injection molding low cost parts.
  • a PTFE multi-well plate would be useful for assays that require no protein binding by the support.
  • a PTFE plate in combination with a low protein binding membrane would have substantial utility. Until the present invention, such a device was not available due to its cost and the limitations of technology.
  • the current format of choice for multi-well membrane filters is a 96 well plate with a support that is made from injection-molded resins such as polyethylene, styrene and acrylic. 12 and 24 well formats preceded the 96 well plate, but as robotics improved and sample volumes have mushroomed, the need for more assays per plate (higher well density) has increased. Moreover, the volume of the typical assay is shrinking dramatically because of the costs of the material being assayed, proteins, nucleic acids and the like, the costs of the solvents, buffers, enzymes and the like, and improvements in detection technology. As such, that market requires multiple well membrane filters that have more wells in same area with the wells having smaller volumes. Indeed, formats of 384, 1536, 9600 wells are envisioned.
  • the present invention solves the prior art problems by providing a platform suitable for affixing a membrane that results in a multi-well membrane filter suitable for high throughput screening assays in high density, low volume formats.
  • the current invention allows for quick, inexpensive change over in the manufacturing process without the expensive tooling costs required by the injection molding process.
  • the present invention can provide a multi-well membrane filter that is much cheaper on a per well basis than prior art multi-well membrane filters.
  • the present invention provides a means for using PTFE supports in multi-well membrane filters that are competitive on a per well basis with the current injection molded polyethylene support in the 96 well format.
  • the present invention provides a multi-well membrane filter comprising a support characterized by through holes not having been molded therein; and a membrane filter fixed to said support so at least one side of at least two such through holes are covered such that the device has at least two wells suitable for receiving material to be assayed.
  • the present invention provides a method of producing a multi-well membrane filter device, the method comprising 1) selecting a pre-formed support suitable for affixing a membrane thereto; 2) removing material from such pre-formed support so as to form substantially aligned through holes therein; 3) selecting a membrane suitable for filtering solutions in a laboratory setting; and 4) forming wells by laminating the membrane to the support.
  • Figure 1 provides top and sectional views of a multi-well filter device with different well shapes and an underdrain laminated thereto
  • the present invention provides a multi-well membrane filter, the filter comprising a support characterized by through holes not having been molded therein; and a membrane filter fixed to said support so at least one side of at least two such through holes are covered such that the device has at least two wells suitable for receiving material to be assayed.
  • the support may be made of glass, metallic materials, ceramic materials, elastomeric materials and coated cellulosic materials.
  • the support includes polymeric material.
  • Polymeric materials suitable for the present invention include polyethylene, acrylic, PTFE, polycarbonate and styrene.
  • the plate height is less than one quarter inch thick.
  • the multi-well membrane filter of the present invention is configured to have at least 96 wells.
  • wells in a specific device may have different volumes.
  • individual wells have a volume in the range of 50 to 150 microliters. More preferably, the individual wells have a volume in the range of 70 to 130 microliters.
  • a volume of about 100 to 120 microliters is preferred. It is envisioned that for formats greater than the 384-well format, the volume requirements will diminish.
  • the wells may also have different shapes.
  • the multi-well membrane filter of the present invention will have an underdrain laminated to the opposite side of the membrane to facilitate collection of filtrate.
  • the membrane contains patterned porous structures.
  • the present invention provides a method of producing a multi-well membrane filter device, the method comprising selecting a pre-formed support suitable for affixing a membrane thereto; removing material from such pre-formed support so as to form substantially aligned through holes therein; selecting a membrane suitable for filtering solutions in a laboratory setting; and forming wells by laminating the membrane to the support.
  • the method of the present invention includes extruding a material of
  • the through holes in the pre-formed support are made by selectively drilling, punching, burning or dissolving material to be removed.
  • the preferred method of laminating the membrane to the support is in a web converting process.
  • Preferred methods of laminating include diffusion bonding, adhesive bonding, welding and thermal bonding.
  • Figure 1 provides an example of the present invention.
  • a rigid sheet 10 is infused with a matrix of wells.
  • the wells could be pre-punched or they could be produced online within an assembly process, such as a web converting process.
  • the perforated sheet could be presented to the assembly machine precut and stacked or on a continuous web and cut to size online.
  • the well matrix will be determined by the end users needs, but it could have numerous configurations and the wells do not necessarily need to be all of the same shape or size.
  • Figure 1, Top View provides the wells of the present invention having round, square, and other shapes. Virtually any shape that is required for the product may be provided.
  • the rigid sheet 10 allows for easy handling during manufacturing and easy handling during use by the end user (a human or a robot).
  • the web process uses sheet stock
  • using sheet/roll stock as the starting material allows for a variety of resins and support thicknesses because most vendors of sheet stock supply a wide range of resins and thicknesses to be used with this type of assembly process.
  • By varying the thickness of the sheet various products could be developed with different starting well volumes. One could also use the same sheet thickness and vary the volume by removing more material when the through holes are created.
  • a membrane 14 is attached to the perforated sheet.
  • the membrane could be completely hydrophobic or hydrophilic or it could be hydrophilic with hydrophobic regions 18.
  • the present invention may also be used in connection with related case no. MCA-474 filed concurrently herewith that is related to porous structures having selected functional patterns upon and/or in them. That invention is particularly related to porous structures such as membranes that have a series of one or more patterns of porous and non-porous areas. Such patterned porous structures may be laminated on the support structure of the present invention. It is envisioned that non-porous regions of the membrane will situated where the hydrophobic region 18 is in Figure 1.
  • the means of laminating; that is, attachment could be any of the following: 1. Heat (thermal, ultrasonic, vibration)- The membrane and perforated sheet are held together under pressure. Then ultrasonic energy, vibration energy, or thermal energy applies heat. The melted resin will be pushed into the pores of the membrane. 2. Epoxy- A very thin film of epoxy (air cured, heat cured, UV cured) is applied to 1 side of the perforated sheet. Then the membrane is applied and held in place at specific pressure and cured. If UN is used for curing, then the sheet and or the membrane must be transparent to the UN light. Although epoxy is discussed in this disclosure, most adhesives (silicone based, acrylic based, etc.) will work as described above as long as they are compatible with the rigid sheet, membrane and assay.
  • Solvent- A solvent that dissolves the perforated sheets only is applied to 1 surface of the perforated sheet or to the membrane. The membrane is pressed onto the perforated sheet and held until the excess solvent has been dispersed. The dissolved resin will be pushed into the pores of the membrane.
  • a solvent that can dissolve both the perforated sheet and the membrane is applied only to the perforated sheet. The membrane is pressed onto the perforated sheet and held until the excess solvent has been dispersed.
  • the dissolved resin from the membrane and the dissolved resin from the perforated sheet mix and solidify.
  • Durapore® membrane produced by Millipore Corporation would be solvent bonded to a polycarbonate sheet with methylene chloride. It is critical that the solvent be compatible with the materials used to produce the support and the membrane.
  • the present invention also provides a process of making a multi well membrane with limited cross talk. Specifically the process further comprises the step of making the seal formed around the individual wells after the lamination step impervious to the filtrate.
  • the seal between the support and the membrane needs only to be secure enough to prevent the membrane from releasing from the sheet and prevent the fluid from crossing from well to well between the sheet and the surface of the membrane.
  • it is imperative that the seal formed around the individual wells is impervious to the filtrate so that cross talk between the wells is avoided.
  • the present invention provides a variety of different means of making the seal formed around the individual wells after the lamination step impervious to the filtrate.
  • FIG. 1 presents the use of an underdrain 20 with present invention.
  • Underdrains are typically vacuum formed or molded and may be added after the membrane has been laminated it may added at same time as the membrane. The same bonding technologies described above would be used during lamination of the underdrain 20.
  • the present invention results in a superior multi-well membrane device process because the manufacturing cost thereof on a well-to-well basis will be much less expensive than prior art because the support or rigid sheet will be less expensive than a molded part.
  • the present invention results in a superior multi-well membrane device process because the assembly process could be a web converting process. Use of such process would further reduce assembly costs.
  • the present invention results in a superior multi-well membrane device process because multiple resins and thickness are readily available for the rigid sheets. Moreover, product design variations (chemical compatabilities, geometries, thicknesses and the like) can be made with minor die punch changes (this cannot be done with injection molds) and minor adjustments to the assembly equipment.
  • the present invention results in a superior multi-well membrane device process because the rigid sheet concept allows for multiple line extensions using the same assembly equipment.
  • the present invention results in a superior multi-well membrane device because it provides substantially increased well density, lower volume, tailored volume in a single card and the ability to use PTFE on a cost effective basis.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Water Supply & Treatment (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Laminated Bodies (AREA)

Abstract

The present invention provides multi-well membrane filter and methods of producing same, the multi-well membrane filter comprising a non-injection molded support and filter membrane laminated thereto, the method particularly adapted for producing multi-well membrane filters that have a substantial well density and small volume sample wells.

Description

HIGH THROUGHPUT SCREENING CARD Inventor: Brian Foley
This application relates to co-pending U.S. Applications "Three Dimensional Patterned Porous Structures," our reference number MCA-482 and "Patterned Porous Structures, " our reference number MCA-474, both filed concurrently herewith.
BACKGROUND OF THE INVENTION
The Multiscreen® multiple well membrane filter for laboratory and research use, produced by Millipore Corporation, is used for laboratory assays. These filters and its competitive products are made by first creating a support plate by injection molding a resin. Typically, polyethylene, Barex™ polymer, acrylic or styrene is used as the resin. The support plate would have a number of through holes, with the wall of such holes serving as the side wall (circular well) or walls (multi-hedral well) of the wells. As such, the resin in its injection-molded form must not interfere with the laboratory assay it is used for.
The multi-well device is then created by cutting filter membrane into discs and attaching the discs to one side of each through hole, thereby creating the wells. Such filter membrane is typically attached to the support by bonding, either thermal or ultrasonic. This is a labor-intensive operation, adding substantially to the cost of manufacturing.
As the injection molded support plates require a mold, a mold has to be produced for each device. The process of producing a mold for use in production first requires the production of a prototype mold. Such molds cost around $50,000. Once the final design of the product is agreed upon, a production mold is made. The cost of a production mold varies with the number of cavities intended for the injection-molding tool. For example, a one-cavity tool for 96 well plate production requires a mold that typically costs $90,000. A two-cavity tool for 96 well plate production requires a mold that typically costs $160,000. A limitation of the molds is that they are suitable only for similar materials. One could not use the polyethylene mold to produce a styrene support. This limits the products that can be made available because it is not cost effective to produce the same plate design from two different materials due to the cost of capital and the time to recoup the investment.
For example, it would be beneficial to offer a variety of materials for supports so the researcher can avoid materials that may leach extractables into their assay. Indeed, the use of Teflon® polytetraflouroethylene ("PTFE"), a substantially inert material, is not used to produce supports because it is not a cost effective alternative for injection molding low cost parts. For example, a PTFE multi-well plate would be useful for assays that require no protein binding by the support. Indeed, a PTFE plate in combination with a low protein binding membrane would have substantial utility. Until the present invention, such a device was not available due to its cost and the limitations of technology.
The current format of choice for multi-well membrane filters is a 96 well plate with a support that is made from injection-molded resins such as polyethylene, styrene and acrylic. 12 and 24 well formats preceded the 96 well plate, but as robotics improved and sample volumes have mushroomed, the need for more assays per plate (higher well density) has increased. Moreover, the volume of the typical assay is shrinking dramatically because of the costs of the material being assayed, proteins, nucleic acids and the like, the costs of the solvents, buffers, enzymes and the like, and improvements in detection technology. As such, that market requires multiple well membrane filters that have more wells in same area with the wells having smaller volumes. Indeed, formats of 384, 1536, 9600 wells are envisioned.
Unfortunately, the injection molding process has severe limitations beyond the current 96 well format. There are substantial manufacturing hurdles with such higher density formats such as molding (more plastic, higher piece part cost, tool building and maintenance costs) and assembly (stricter tolerances are required for cutting and sealing membrane on the wells.) Moreover, the overall size of the plate cannot expand much, if at all, due to the customers already significant sunk costs in laboratory automation.
The present invention solves the prior art problems by providing a platform suitable for affixing a membrane that results in a multi-well membrane filter suitable for high throughput screening assays in high density, low volume formats. The current invention allows for quick, inexpensive change over in the manufacturing process without the expensive tooling costs required by the injection molding process. Moreover, the present invention can provide a multi-well membrane filter that is much cheaper on a per well basis than prior art multi-well membrane filters. Lastly, the present invention provides a means for using PTFE supports in multi-well membrane filters that are competitive on a per well basis with the current injection molded polyethylene support in the 96 well format.
SUMMARY OF THE INVENTION
The present invention provides a multi-well membrane filter comprising a support characterized by through holes not having been molded therein; and a membrane filter fixed to said support so at least one side of at least two such through holes are covered such that the device has at least two wells suitable for receiving material to be assayed.
The present invention provides a method of producing a multi-well membrane filter device, the method comprising 1) selecting a pre-formed support suitable for affixing a membrane thereto; 2) removing material from such pre-formed support so as to form substantially aligned through holes therein; 3) selecting a membrane suitable for filtering solutions in a laboratory setting; and 4) forming wells by laminating the membrane to the support. BRIEF DESCRIPTION OF THE FIGURES
Figure 1 provides top and sectional views of a multi-well filter device with different well shapes and an underdrain laminated thereto
DETAILED DESCRIPTION OF THE SPECIFIC EMBODIMENT
The present invention provides a multi-well membrane filter, the filter comprising a support characterized by through holes not having been molded therein; and a membrane filter fixed to said support so at least one side of at least two such through holes are covered such that the device has at least two wells suitable for receiving material to be assayed.
Preferably, the support may be made of glass, metallic materials, ceramic materials, elastomeric materials and coated cellulosic materials. In a more preferable embodiment, the support includes polymeric material. Polymeric materials suitable for the present invention include polyethylene, acrylic, PTFE, polycarbonate and styrene.
Preferably, the plate height is less than one quarter inch thick. The prior made no suggestion for the plate of the present invention because the volume requirements would have necessitated a plate of a large thickness, i.e., greater than one half inch. At such thickness, there is no motivation to using anything other than molding due to the costs of that process.
Preferably, the multi-well membrane filter of the present invention is configured to have at least 96 wells. In such a configuration, wells in a specific device may have different volumes. Preferably, individual wells have a volume in the range of 50 to 150 microliters. More preferably, the individual wells have a volume in the range of 70 to 130 microliters. For the 384-well format, a volume of about 100 to 120 microliters is preferred. It is envisioned that for formats greater than the 384-well format, the volume requirements will diminish. The wells may also have different shapes. In a preferred embodiment, the multi-well membrane filter of the present invention will have an underdrain laminated to the opposite side of the membrane to facilitate collection of filtrate.
In a preferred embodiment of the present invention, the membrane contains patterned porous structures.
The present invention provides a method of producing a multi-well membrane filter device, the method comprising selecting a pre-formed support suitable for affixing a membrane thereto; removing material from such pre-formed support so as to form substantially aligned through holes therein; selecting a membrane suitable for filtering solutions in a laboratory setting; and forming wells by laminating the membrane to the support.
Preferably, the method of the present invention includes extruding a material of
-interest to form the pre-formed support.
Preferably, the through holes in the pre-formed support are made by selectively drilling, punching, burning or dissolving material to be removed.
The preferred method of laminating the membrane to the support is in a web converting process. Preferred methods of laminating include diffusion bonding, adhesive bonding, welding and thermal bonding.
Figure 1 provides an example of the present invention. A rigid sheet 10 is infused with a matrix of wells. The wells could be pre-punched or they could be produced online within an assembly process, such as a web converting process. For example, the perforated sheet could be presented to the assembly machine precut and stacked or on a continuous web and cut to size online. The well matrix will be determined by the end users needs, but it could have numerous configurations and the wells do not necessarily need to be all of the same shape or size. Figure 1, Top View, provides the wells of the present invention having round, square, and other shapes. Virtually any shape that is required for the product may be provided.
The rigid sheet 10 allows for easy handling during manufacturing and easy handling during use by the end user (a human or a robot). As the web process uses sheet stock, using sheet/roll stock as the starting material allows for a variety of resins and support thicknesses because most vendors of sheet stock supply a wide range of resins and thicknesses to be used with this type of assembly process. By varying the thickness of the sheet, various products could be developed with different starting well volumes. One could also use the same sheet thickness and vary the volume by removing more material when the through holes are created.
After the perforated sheet is produced with the appropriate array, a membrane 14 is attached to the perforated sheet. The membrane could be completely hydrophobic or hydrophilic or it could be hydrophilic with hydrophobic regions 18.
The present invention may also be used in connection with related case no. MCA-474 filed concurrently herewith that is related to porous structures having selected functional patterns upon and/or in them. That invention is particularly related to porous structures such as membranes that have a series of one or more patterns of porous and non-porous areas. Such patterned porous structures may be laminated on the support structure of the present invention. It is envisioned that non-porous regions of the membrane will situated where the hydrophobic region 18 is in Figure 1.
A variety of laminating process is envisioned, yet the below description is not exclusive. Those of ordinary skill in the art would appreciate other means of attaching two layers together like those described herein.
The means of laminating; that is, attachment could be any of the following: 1. Heat (thermal, ultrasonic, vibration)- The membrane and perforated sheet are held together under pressure. Then ultrasonic energy, vibration energy, or thermal energy applies heat. The melted resin will be pushed into the pores of the membrane. 2. Epoxy- A very thin film of epoxy (air cured, heat cured, UV cured) is applied to 1 side of the perforated sheet. Then the membrane is applied and held in place at specific pressure and cured. If UN is used for curing, then the sheet and or the membrane must be transparent to the UN light. Although epoxy is discussed in this disclosure, most adhesives (silicone based, acrylic based, etc.) will work as described above as long as they are compatible with the rigid sheet, membrane and assay.
3. Solvent- A solvent that dissolves the perforated sheets only is applied to 1 surface of the perforated sheet or to the membrane. The membrane is pressed onto the perforated sheet and held until the excess solvent has been dispersed. The dissolved resin will be pushed into the pores of the membrane. In another method, a solvent that can dissolve both the perforated sheet and the membrane is applied only to the perforated sheet. The membrane is pressed onto the perforated sheet and held until the excess solvent has been dispersed. In this method the dissolved resin from the membrane and the dissolved resin from the perforated sheet mix and solidify. For example, Durapore® membrane produced by Millipore Corporation, would be solvent bonded to a polycarbonate sheet with methylene chloride. It is critical that the solvent be compatible with the materials used to produce the support and the membrane.
4. Νon-contact fusion bonding- The surface of the perforated sheet is heated to it's melting point. The heat source is quickly removed and the membrane is pressed and held until the resin solidifies.
5. Diffusion bonding- The membrane and perforated sheet are pressed together at a "critical" temperature and pressure. At the critical point the resins will molecularly mix and solidify.
The present invention also provides a process of making a multi well membrane with limited cross talk. Specifically the process further comprises the step of making the seal formed around the individual wells after the lamination step impervious to the filtrate. In applications where filtrate collection is not required, the seal between the support and the membrane needs only to be secure enough to prevent the membrane from releasing from the sheet and prevent the fluid from crossing from well to well between the sheet and the surface of the membrane. In applications that require filtrate collection, it is imperative that the seal formed around the individual wells is impervious to the filtrate so that cross talk between the wells is avoided.
The present invention provides a variety of different means of making the seal formed around the individual wells after the lamination step impervious to the filtrate.
1) Collapsing the pores in the membrane with heat and prior to laminating to the support. Collapsing the pores could possibly be done at the same time as laminating.
2) After laminating, break or remove membrane from between thee wells by die cutting, ultrasonic vibration or heat.
3) Using a hydrophobic barrier pre or post laminating.
4) Filling the non-well forming membrane pores with epoxy.
5) Using solvents that will solvate the sheet and the membrane, thereby collapsing the pores in non-well forming membrane.
6) Using solvents that will dissolve only the rigid sheet. This will fill the pores in the non well-forming membrane with material from the rigid sheet.
The Sectional View of Figure 1 presents the use of an underdrain 20 with present invention. Underdrains are typically vacuum formed or molded and may be added after the membrane has been laminated it may added at same time as the membrane. The same bonding technologies described above would be used during lamination of the underdrain 20. The present invention results in a superior multi-well membrane device process because the manufacturing cost thereof on a well-to-well basis will be much less expensive than prior art because the support or rigid sheet will be less expensive than a molded part.
The present invention results in a superior multi-well membrane device process because the assembly process could be a web converting process. Use of such process would further reduce assembly costs.
The present invention results in a superior multi-well membrane device process because multiple resins and thickness are readily available for the rigid sheets. Moreover, product design variations (chemical compatabilities, geometries, thicknesses and the like) can be made with minor die punch changes (this cannot be done with injection molds) and minor adjustments to the assembly equipment.
The present invention results in a superior multi-well membrane device process because the rigid sheet concept allows for multiple line extensions using the same assembly equipment.
The present invention results in a superior multi-well membrane device because it provides substantially increased well density, lower volume, tailored volume in a single card and the ability to use PTFE on a cost effective basis.
The above examples are not to be construed as limiting the scope of the subject invention, which is set forth in the claims below. Those of ordinary skill in the art will appreciate the types of membranes appropriate to practice the present invention.

Claims

1. A multi-well membrane filter, the filter comprising: a support characterized by through holes not having been molded therein; and a membrane filter fixed to said support so at least one side of at least two such through holes are covered such that the device has at least two wells suitable for receiving material to be assayed.
2. The multi-well membrane filter of claim 1, wherein the support includes glass.
3. The multi-well membrane filter of claim 1, wherein the support includes metallic materials.
4. The multi-well membrane filter of claim 1, wherein the support includes ceramic materials.
5. The multi-well membrane filter of claim 1, wherein the support includes elastomeric materials.
6. The multi-well membrane filter of claim 1, wherein the support includes coated cellulosic materials.
7. The multi-well membrane filter of claim 1, wherein the support includes a polymeric material.
8. The multi -well membrane filter of claim 2, wherein the polymeric material includes polyethylene.
9. The multi-well membrane filter of claim 2, wherein the polymeric material includes acrylic.
10. The multi-well membrane filter of claim 2, wherein the polymeric material includes PTFE.
11. The multi -well membrane filter of claim 2, wherein the polymeric material includes polycarbonate.
12. The multi-well membrane filter of claim 2, wherein the polymeric material includes styrene.
13. The multi-well membrane filter of claim 1, wherein the support and membrane are configured to have at least 96 wells.
14. The multi -well membrane filter of claim 13, wherein the support and membrane are configured to have at least 384 wells.
15. The multi -well membrane filter of claim 1, wherein at least two wells have different volumes.
16. The multi-well membrane filter of claims 1 and 14, wherein the volume of each well is in the range of 50 to 150 microliters.
17. The multi-well membrane filter of claim 16, wherein the volume of each well is in the range of 70 to 130 microliters.
18. The multi -well membrane filter of claim 1, wherein at least two cells have different shapes.
19. The multi-well membrane filter of claim 1 further comprising an underdrain laminated to the opposite side of the membrane.
20. The multi-well membrane filter of claim 1, wherein the membrane contains patterned porous structures.
21. A method of producing a multi-well membrane filter device, the method comprising: selecting a pre-formed support suitable for affixing a membrane thereto; removing material from such pre-formed support so as to form substantially aligned through holes therein; selecting a membrane suitable for filtering solutions in a laboratory setting; and forming wells by laminating the membrane to the support.
22. The method of claim 21 further comprising extruding a material to form the preformed support.
23. The method of claim 21, wherein material is removed from the pre-formed support by selectively drilling out material to be removed.
24. The method of claim 21, wherein material is removed from the pre-formed support by selectively punching out material to be removed.
25. The method of claim 21, wherein material is removed from the pre-formed support by selectively burning material to be removed.
26. The method of claim 21, wherein material is removed from the pre-formed support by selectively dissolving material to be removed.
27. The method of claim 21, wherein the membrane is laminated to the support in a web converting process.
28. The method of claim 21, wherein the membrane is laminated to the support by diffusion bonding.
29. The method of claim 21, wherein the membrane is laminated to the support by adhesive bonding.
30. The method of claim 21, wherein the membrane is laminated to the support by welding.
31. The method of claim 21, wherein the membrane is laminated to the support by thermal bonding.
32. The method of claim 21 further comprising the step of making the seal formed around the individual wells after the lamination step impervious to the filtrate.
EP00965123A 1999-09-17 2000-09-18 High throughput screening card Ceased EP1214139A2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US15456599P 1999-09-17 1999-09-17
US154565P 1999-09-17
PCT/US2000/025585 WO2001019502A2 (en) 1999-09-17 2000-09-18 High throughput screening card

Publications (1)

Publication Number Publication Date
EP1214139A2 true EP1214139A2 (en) 2002-06-19

Family

ID=22551833

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00965123A Ceased EP1214139A2 (en) 1999-09-17 2000-09-18 High throughput screening card

Country Status (2)

Country Link
EP (1) EP1214139A2 (en)
WO (1) WO2001019502A2 (en)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6742659B2 (en) 2000-05-18 2004-06-01 Millipore Corporation Multiple well plate with adhesive bonded filter
US6439036B1 (en) 2000-06-13 2002-08-27 Symyx Technologics, Inc. Method for evaluating a test fluid
US6455007B1 (en) 2000-06-13 2002-09-24 Symyx Technologies, Inc. Apparatus and method for testing compositions in contact with a porous medium
EP1302241A2 (en) * 2000-06-13 2003-04-16 Symyx Technologies, Inc. Apparatus and method for evaluating a test fluid
WO2003004690A2 (en) * 2001-07-06 2003-01-16 454$m(3) CORPORATION Method for isolation of independent, parallel chemical micro-reactions using a porous filter
GB2377990B (en) * 2001-07-17 2003-11-12 Vivascience Ltd Device for simultaneous processing of discrete quantities of flowable material
EP1281966A3 (en) * 2001-07-30 2003-06-18 Fuji Photo Film Co., Ltd. Method and apparatus for conducting a receptor-ligand reaction
US7211165B2 (en) 2003-01-22 2007-05-01 Millipore Corporation Method of forming multiwell filtration plates
CN100499316C (en) * 2003-04-14 2009-06-10 哈格雷夫斯技术公司 Pump motor with bearing preload
US20060286555A1 (en) * 2003-08-21 2006-12-21 Van Beuningen Marinus G J Microarray support for bioprobe synthesis
EP2404672A1 (en) * 2010-07-06 2012-01-11 Universiteit Twente High troughput multiwell system for culturing 3D tissue constructs in-vitro or in-vivo, method for producing said multiwell system and methods for preparing 3D tissue constructs from cells using said multiwell system
FR3116009A1 (en) 2020-11-06 2022-05-13 Preciphos Production of bio-functionalized filter chip arrays
FR3116008A1 (en) 2020-11-06 2022-05-13 Preciphos Production of biofunctionalized filter chips
WO2025137016A1 (en) * 2023-12-21 2025-06-26 Illumina, Inc. Reduced area array of pre-aliquoted reagent cartridges for a library preparation system

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4797259A (en) * 1986-12-15 1989-01-10 Pall Corporation Well-type diagnostic plate device
EP0302933A4 (en) * 1987-02-24 1990-04-10 Bionique Lab Inc Disposable immunoassay and biochemical test device suitable for field and office use.
US5342581A (en) * 1993-04-19 1994-08-30 Sanadi Ashok R Apparatus for preventing cross-contamination of multi-well test plates
ATE214633T1 (en) * 1993-10-28 2002-04-15 Houston Advanced Res Ct MICROFABRICATED POROUS FLOW DEVICE
GB9521775D0 (en) * 1995-10-24 1996-01-03 Pa Consulting Services Microwell plates
US6090251A (en) * 1997-06-06 2000-07-18 Caliper Technologies, Inc. Microfabricated structures for facilitating fluid introduction into microfluidic devices
ATE477850T1 (en) * 1998-01-12 2010-09-15 Massachusetts Inst Technology DEVICE FOR PERFORMING MICROTESTS
DE19904784A1 (en) * 1999-02-05 2000-08-10 Deutsches Krebsforsch Flow device and its use for binding polymers to membrane surfaces

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0119502A3 *

Also Published As

Publication number Publication date
WO2001019502A3 (en) 2001-08-09
WO2001019502A2 (en) 2001-03-22

Similar Documents

Publication Publication Date Title
KR100572207B1 (en) Bonding method of plastic microchip
EP1214139A2 (en) High throughput screening card
US6848462B2 (en) Adhesiveless microfluidic device fabrication
EP1115573B1 (en) Methods of fabricating polymeric structures incorporating microscale fluidic elements
Becker et al. Polymer microfabrication technologies for microfluidic systems
EP1015878B1 (en) Methods for fabricating enclosed microchannel structures
EP2114570B1 (en) Microfluidic device
US8506833B2 (en) Molded body, method for producing the body and use thereof
US6627291B1 (en) Three dimensional patterned porous structures
US7658886B2 (en) Universal filtration plate
US8182766B2 (en) Universal filter plate
EP1585595B1 (en) A method of forming multiwell filtration plates
US6463647B1 (en) Method of making an extruded high density assay plate
EP1992469A1 (en) Method for producing a membrane in a framework
JP5251983B2 (en) Microchip manufacturing method
JP2008304352A (en) Method of bonding substrate for flow channel device and flow channel device
WO1999047352A1 (en) Extruded high density assay plate
DE19851644B4 (en) Method for joining microstructured workpieces made of plastic and use of the method for the production of components
KR101597210B1 (en) Method for forming microchannels of lab-on-a-chip
GB2348622A (en) Moulded filter plates
EP2769767A2 (en) Non-planar moulded article, method for producing the same, its use, method for producing a micro framework and its use
WO2025245880A1 (en) Micro-fluidic chip and manufacturing method therefor, and droplet preparation method
DE112011106142B3 (en) Openwork thermoplastic elastomer membrane, its use and process for its manufacture
HK1119722A (en) Functional materials and novel methods for the fabrication of microfluidic devices

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20020409

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

17Q First examination report despatched

Effective date: 20021022

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: MILLIPORE CORPORATION

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN REFUSED

18R Application refused

Effective date: 20031113

RBV Designated contracting states (corrected)

Designated state(s): AT BE DE GB