WO1991015750A1 - Microfabricated device for biological cell sorting - Google Patents

Microfabricated device for biological cell sorting Download PDF

Info

Publication number
WO1991015750A1
WO1991015750A1 PCT/GB1991/000542 GB9100542W WO9115750A1 WO 1991015750 A1 WO1991015750 A1 WO 1991015750A1 GB 9100542 W GB9100542 W GB 9100542W WO 9115750 A1 WO9115750 A1 WO 9115750A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
microfabricated
cell sorting
biological cell
microfabricated device
Prior art date
Application number
PCT/GB1991/000542
Other languages
French (fr)
Inventor
Paul Henry Kaye
Mark Christopher Tracey
Original Assignee
Carri-Med Limited
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 Carri-Med Limited filed Critical Carri-Med Limited
Publication of WO1991015750A1 publication Critical patent/WO1991015750A1/en

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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
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04—Cell isolation or sorting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0622—Valves, specific forms thereof distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N11/00—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Electro-optical investigation, e.g. flow cytometers
    • G01N15/149—

Definitions

  • This invention relates to the sorting of biological cells into spatially separate sub groups.
  • the criteria for sorting may be applied to measurements obtained by any technique or techniques suitable for microfabricated or electronic implementation on a substrate.
  • Microfabrication and microelectronic techniques offer a number of actual and potential measurement techniques that may be applied to characterize biological cells.
  • PCT/GB91/00289 and morphological measurements.
  • morphological measurements When suitably implemented such techniques can be applied on a cell by cell basis.
  • microelectromechani ⁇ al structures and their formation by selective CVD techniques, are disclosed in: "Selective Chemical Vapor Deposition of Tungsten for Mi ⁇ roelectromechani ⁇ al Structures" by N. C. MACDONALD et al. , Sensors and Actuators, 20 (1989) 123-133.
  • the so-called “microtweezers” are activated by control voltages applied to electrodes.
  • such a machine is implemented by utilising a microfabricated moveable structure, preferably microfabricated beams, to direct cells between distinct spatial locations.
  • FIG. 1 is a topologi ⁇ al plan view of a substrate on which a cell sorter is formed.
  • the cells to be sorted whose diameters may be only a few micrometres, are fed sequentially from an entry port 1, via a guiding structure 2, past a generalised sensing device or zone 3.
  • the deflectable beams 4, 5, 6, are set into appropriate states to direct the cell into a particular destination, for example, a hole 7, 8, 9 or 10 etched through the substrate.
  • the destination is structure 9.
  • the beams, along with associated bifurcations can be extended to a tree structure of ' n' levels thereby yielding 2 possible sorting sub ranges.
  • the absolute lengths of the channels are as short as possible while maintaining compatibility with interconnecting structures.
  • the shafts 1, 3, 7-10 may be fabricated by selective etching as disclosed in the copending International Patent Application referred to above; the etched substrate is closed by a glass/silica cover, thereby forming the channels as tunnels.
  • Typical dimensions of the entry port 1 are 500 ⁇ m or less square; of the sensing zone about 100 ⁇ m square; of the channels about 5 to 10 ⁇ m in width and depth; of the holes (shafts) 7 - 10 about 500 ⁇ m or less square; and of the beams, which are typically of constant rectangular section, about 150 ⁇ m long by 3 ⁇ m square.
  • the overall dimensions of the device could be l ⁇ m square.
  • the beams are activated by selective control voltages applied as signals for control circuitry (not shown) operated, for example, under the control of a microprocessor or other computer.
  • the computer is programmed to control the beams' deflection in response to the desired cell-sorting procedural steps.

Abstract

Apparatus for sorting cells into spatially separate sub-groups, comprising a microfabricated moveable structure (4, 5, 6) for directing cells between distinct spatial locations.

Description

Microfabricated Device for Biological Cell Sorting
This invention relates to the sorting of biological cells into spatially separate sub groups. The criteria for sorting may be applied to measurements obtained by any technique or techniques suitable for microfabricated or electronic implementation on a substrate.
Microfabrication and microelectronic techniques offer a number of actual and potential measurement techniques that may be applied to characterize biological cells.
Examples of these are microrheological measurements as disclosed in International Patent Application No.
PCT/GB91/00289 and morphological measurements. When suitably implemented such techniques can be applied on a cell by cell basis.
When characterizing a population of cells it can be of interest to workers to be able to isolate a sub population whose measured parameters lie within certain bounds. This could enable, for example, the σulturing of a cell line from sorted cells possessing a certain property or properties of interest.
we have discovered that recent developments in microfabrication, namely the development of controlled, deflectable, microbeams capable of deflections in the order of a few micrometres; may be used to provide the component parts of microfabricated cell sorters. Relevant microelectromechaniσal structures, and their formation by selective CVD techniques, are disclosed in: "Selective Chemical Vapor Deposition of Tungsten for Miσroelectromechaniσal Structures" by N. C. MACDONALD et al. , Sensors and Actuators, 20 (1989) 123-133. The so-called "microtweezers" are activated by control voltages applied to electrodes.
According to the current invention such a machine is implemented by utilising a microfabricated moveable structure, preferably microfabricated beams, to direct cells between distinct spatial locations.
A particular implementation of the invention is shown in the drawing, which is a topologiσal plan view of a substrate on which a cell sorter is formed. In this example the cells to be sorted, whose diameters may be only a few micrometres, are fed sequentially from an entry port 1, via a guiding structure 2, past a generalised sensing device or zone 3. Depending upon the result of the measurement and its interpretation the deflectable beams 4, 5, 6, are set into appropriate states to direct the cell into a particular destination, for example, a hole 7, 8, 9 or 10 etched through the substrate. In the example shown the destination is structure 9. The beams, along with associated bifurcations can be extended to a tree structure of ' n' levels thereby yielding 2 possible sorting sub ranges.
The absolute lengths of the channels are as short as possible while maintaining compatibility with interconnecting structures. The shafts 1, 3, 7-10 may be fabricated by selective etching as disclosed in the copending International Patent Application referred to above; the etched substrate is closed by a glass/silica cover, thereby forming the channels as tunnels.
Typical dimensions of the entry port 1 are 500μm or less square; of the sensing zone about 100 μm square; of the channels about 5 to 10μm in width and depth; of the holes (shafts) 7 - 10 about 500 μm or less square; and of the beams, which are typically of constant rectangular section, about 150μm long by 3μm square.
The overall dimensions of the device could be lσm square.
The beams are activated by selective control voltages applied as signals for control circuitry (not shown) operated, for example, under the control of a microprocessor or other computer. The computer is programmed to control the beams' deflection in response to the desired cell-sorting procedural steps.

Claims

Claims :
1. Apparatus for sorting cells into spatially separate sub-groups, comprising a microfabricated moveable structure (4, 5, 6) for directing cells between distinct spatial locations.
2. Method for sorting cells into spatially separate sub-groups, comprising directing the cells into distinct spatial locations using a microfabricated moveable structure.
PCT/GB1991/000542 1990-04-09 1991-04-08 Microfabricated device for biological cell sorting WO1991015750A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9008044.1 1990-04-09
GB909008044A GB9008044D0 (en) 1990-04-09 1990-04-09 Microfabricated device for biological cell sorting

Publications (1)

Publication Number Publication Date
WO1991015750A1 true WO1991015750A1 (en) 1991-10-17

Family

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Country Status (2)

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GB (1) GB9008044D0 (en)
WO (1) WO1991015750A1 (en)

Cited By (48)

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WO1993022054A1 (en) * 1992-05-01 1993-11-11 Trustees Of The University Of Pennsylvania Analysis based on flow restriction
US5304487A (en) * 1992-05-01 1994-04-19 Trustees Of The University Of Pennsylvania Fluid handling in mesoscale analytical devices
EP0616218A1 (en) * 1993-03-16 1994-09-21 Hitachi, Ltd. Micro-reactor device and minute sample analysis system using the same
US5427946A (en) * 1992-05-01 1995-06-27 Trustees Of The University Of Pennsylvania Mesoscale sperm handling devices
US5486335A (en) * 1992-05-01 1996-01-23 Trustees Of The University Of Pennsylvania Analysis based on flow restriction
US5498392A (en) * 1992-05-01 1996-03-12 Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification device and method
DE19520298A1 (en) * 1995-06-02 1996-12-05 Bayer Ag Sorting device for biological cells or viruses
US5587128A (en) * 1992-05-01 1996-12-24 The Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification devices
US5726026A (en) * 1992-05-01 1998-03-10 Trustees Of The University Of Pennsylvania Mesoscale sample preparation device and systems for determination and processing of analytes
US5744366A (en) * 1992-05-01 1998-04-28 Trustees Of The University Of Pennsylvania Mesoscale devices and methods for analysis of motile cells
US5747349A (en) * 1996-03-20 1998-05-05 University Of Washington Fluorescent reporter beads for fluid analysis
WO1998045683A1 (en) * 1997-04-08 1998-10-15 Smithkline Beecham Plc Device for isolating small polymeric beads from a suspension of such beads
US5906732A (en) * 1995-11-17 1999-05-25 Yazaki Corporation Apparatus for separating minute substances in liquid
US5950842A (en) * 1995-02-23 1999-09-14 Natec, Reich, Summer Gmbh & Co. Kg Line connector with 90 degree rotation mechanism
WO1999061888A2 (en) * 1998-05-22 1999-12-02 California Institute Of Technology Microfabricated cell sorter
US6056860A (en) * 1996-09-18 2000-05-02 Aclara Biosciences, Inc. Surface modified electrophoretic chambers
US6193647B1 (en) 1999-04-08 2001-02-27 The Board Of Trustees Of The University Of Illinois Microfluidic embryo and/or oocyte handling device and method
WO2001019516A1 (en) * 1999-09-13 2001-03-22 Hoffmann La Roche Suspension handling system
WO2001049412A1 (en) * 1999-12-30 2001-07-12 Acreo Ab Flow controlling device and method
WO2002001189A1 (en) * 2000-06-26 2002-01-03 Gnothis Holding S.A. Method for selecting particles
US6432630B1 (en) 1996-09-04 2002-08-13 Scandinanian Micro Biodevices A/S Micro-flow system for particle separation and analysis
WO2003025563A1 (en) * 2001-09-16 2003-03-27 Chemometec A/S Method and a system for detecting and optionally isolating a rare event particle
US6540895B1 (en) * 1997-09-23 2003-04-01 California Institute Of Technology Microfabricated cell sorter for chemical and biological materials
WO2003060486A1 (en) * 2002-01-10 2003-07-24 Board Of Regents, The University Of Texas System Flow sorting system and methods regarding same
WO2003078065A1 (en) * 2002-03-14 2003-09-25 Micronics, Inc. Microfluidic channel network device
EP1499453A1 (en) * 2002-04-17 2005-01-26 Cytonome, Inc. Method and apparatus for sorting particles
EP1567845A2 (en) * 2002-07-08 2005-08-31 John S. Foster Method and apparatus for sorting biological cells with a mems device
US6953676B1 (en) 1992-05-01 2005-10-11 Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification device and method
WO2007084392A2 (en) * 2006-01-13 2007-07-26 Micronics, Inc. Electromagnetically actuated valves for use in microfluidic structures
EP1998884A2 (en) * 2006-03-16 2008-12-10 Visiongate, Inc. Cantilevered coaxial flow injector apparatus and method for sorting particles
US7691333B2 (en) 2001-11-30 2010-04-06 Fluidigm Corporation Microfluidic device and methods of using same
US7749737B2 (en) 2003-04-03 2010-07-06 Fluidigm Corporation Thermal reaction device and method for using the same
US7820427B2 (en) 2001-11-30 2010-10-26 Fluidigm Corporation Microfluidic device and methods of using same
US7833708B2 (en) 2001-04-06 2010-11-16 California Institute Of Technology Nucleic acid amplification using microfluidic devices
US7867454B2 (en) 2003-04-03 2011-01-11 Fluidigm Corporation Thermal reaction device and method for using the same
US7963399B2 (en) 2002-04-17 2011-06-21 Cytonome/St, Llc Method and apparatus for sorting particles
US8007746B2 (en) 2003-04-03 2011-08-30 Fluidigm Corporation Microfluidic devices and methods of using same
US8129176B2 (en) 2000-06-05 2012-03-06 California Institute Of Technology Integrated active flux microfluidic devices and methods
US8623295B2 (en) 2002-04-17 2014-01-07 Cytonome/St, Llc Microfluidic system including a bubble valve for regulating fluid flow through a microchannel
US8658418B2 (en) 2002-04-01 2014-02-25 Fluidigm Corporation Microfluidic particle-analysis systems
WO2014094791A1 (en) * 2012-12-20 2014-06-26 Danmarks Tekniske Universitet Fluid composition analysis device and method
US8828663B2 (en) 2005-03-18 2014-09-09 Fluidigm Corporation Thermal reaction device and method for using the same
US8871446B2 (en) 2002-10-02 2014-10-28 California Institute Of Technology Microfluidic nucleic acid analysis
US9157550B2 (en) 2009-01-05 2015-10-13 The Board Of Trustees Of The University Of Illinois Microfluidic systems and methods
US9339850B2 (en) 2002-04-17 2016-05-17 Cytonome/St, Llc Method and apparatus for sorting particles
US9714443B2 (en) 2002-09-25 2017-07-25 California Institute Of Technology Microfabricated structure having parallel and orthogonal flow channels controlled by row and column multiplexors
US9943847B2 (en) 2002-04-17 2018-04-17 Cytonome/St, Llc Microfluidic system including a bubble valve for regulating fluid flow through a microchannel
US10994273B2 (en) 2004-12-03 2021-05-04 Cytonome/St, Llc Actuation of parallel microfluidic arrays

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US5955029A (en) * 1992-05-01 1999-09-21 Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification device and method
US5744366A (en) * 1992-05-01 1998-04-28 Trustees Of The University Of Pennsylvania Mesoscale devices and methods for analysis of motile cells
US5304487A (en) * 1992-05-01 1994-04-19 Trustees Of The University Of Pennsylvania Fluid handling in mesoscale analytical devices
US5427946A (en) * 1992-05-01 1995-06-27 Trustees Of The University Of Pennsylvania Mesoscale sperm handling devices
US6184029B1 (en) 1992-05-01 2001-02-06 Trustees Of The University Of Pennsylvania Mesoscale sample preparation device and systems for determination and processing of analytes
US5486335A (en) * 1992-05-01 1996-01-23 Trustees Of The University Of Pennsylvania Analysis based on flow restriction
US5498392A (en) * 1992-05-01 1996-03-12 Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification device and method
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US6660517B1 (en) 1992-05-01 2003-12-09 Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification devices
US5587128A (en) * 1992-05-01 1996-12-24 The Trustees Of The University Of Pennsylvania Mesoscale polynucleotide amplification devices
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US5480614A (en) * 1993-03-16 1996-01-02 Hitachi, Ltd. Micro-reactor device for minute sample analysis
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US5950842A (en) * 1995-02-23 1999-09-14 Natec, Reich, Summer Gmbh & Co. Kg Line connector with 90 degree rotation mechanism
US5837200A (en) * 1995-06-02 1998-11-17 Bayer Aktiengesellschaft Sorting device for biological cells or viruses
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US5906732A (en) * 1995-11-17 1999-05-25 Yazaki Corporation Apparatus for separating minute substances in liquid
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US8257666B2 (en) 2000-06-05 2012-09-04 California Institute Of Technology Integrated active flux microfluidic devices and methods
WO2002001189A1 (en) * 2000-06-26 2002-01-03 Gnothis Holding S.A. Method for selecting particles
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WO2003078065A1 (en) * 2002-03-14 2003-09-25 Micronics, Inc. Microfluidic channel network device
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US9943847B2 (en) 2002-04-17 2018-04-17 Cytonome/St, Llc Microfluidic system including a bubble valve for regulating fluid flow through a microchannel
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