US4729949A
Expired / Lapsed
US
⏱️ 0.0 years remaining
System and methods for cell selection
Assignee: National Patent Development Corp
•
Filing: 1983-11-08
•
Granted: 1988-03-08
•
Expires: 2003-11-08
Abstract
Abstract A method for placing individual living cells at identifiable locations is provided comprising the steps of: (a) providing a carrier having a plurality of apertures, the apertures being arranged in an ordered array and being sized to hold individual cells; (b) applying a fluid containing living cells to the carrier; and (c) applying a force to the cells to move the cells into the apertures.
Inventors
- 👤 Arye Weinreb
- 👤 Mordechai Deutsch
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 13:32
CPC Classifications
C; C12; C12M; C12M3/00; G; G01; G01N; G01N15/00; G01N15/10; C12M23/00; C12M23/02; C12M23/12; C12M41/00; C12M41/46; C12M47/00; C12M47/04; B; B01; B01J; B01J2219/00; B01J2219/00274; B01J2219/00277; B01J2219/00279; B01J2219/00306; B01J2219/00313; B01J2219/00315; B01J2219/00317; C40; C40B; C40B60/00; C40B60/14; Y; Y10; Y10T; Y10T436/00; Y10T436/25; Y10T436/25375
Claims Analysis
Total Claims: 52
Claim 1
Independent Claim
338 words
A method for performing on a cell-by-cell basis one or more of the operations of (i) observing or measuring a property of a living cell, (ii) moving a living cell, or (iii) killing a living cell, comprising the steps of: (a) providing a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the positions on the carrier of the holes being identifiable and the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; (b) applying a fluid containing living cells to the first outer surface of the carrier; (c) applying a force to the living cells to move the living cells into the holes; (d) performing on an individual, first living cell located at a first hole having a first position on the carrier one or more of the operations of (i) observing or measuring a property of the first living cell, (ii) moving the first living cell, or (iii) killing the first living cell; and (e) performing on an individual, second living cell located at a second hole having a second position on the carrier one or more of the operations of (i) observing or measuring a property of the second living cell, (ii) moving the second living cell, or (iii) killing the second living cell.
Claim 2
Independent Claim
338 words
A method for performing on a cell-by-cell basis one or more of the operations of (i) observing or measuring a property of a living cell, (ii) moving a living cell, or (iii) killing a living cell, comprising the steps of: (a) providing a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the positions on the carrier of the holes being identifiable and the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; (b) applying a fluid containing living cells to the first outer surface of the carrier; (c) applying a force to the living cells to move the living cells into the holes; (d) performing on an individual, first living cell located at a first hole having a first position on the carrier one or more of the operations of (i) observing or measuring a property of the first living cell, (ii) moving the first living cell, or (iii) killing the first living cell; and (e) performing on an individual, second living cell located at a second hole having a second position on the carrier one or more of the operations of (i) observing or measuring a property of the second living cell, (ii) moving the second living cell, or (iii) killing the second living cell.
Claim 3
Independent Claim
284 words
A method for performing on a cell-by-cell basis the operation of observing or measuring a living cell at two different times, comprising the steps of: (a) providing a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the positions on the carrier of the holes being identifiable and the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; (b) applying a fluid containing living cells to the first outer surface of the carrier; (c) applying a force to the living cells to move the living cells into the holes; (d) observing or measuring at a first time a property of an individual living cell located at one of the holes of the carrier; and (e) observing or measuring at a second time a property of the same individual living cell which was observed or measured in step (d), the cell being located at the same hole of the carrier as in step (d).
Claim 4
Independent Claim
284 words
A method for performing on a cell-by-cell basis the operation of observing or measuring a living cell at two different times, comprising the steps of: (a) providing a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the positions on the carrier of the holes being identifiable and the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; (b) applying a fluid containing living cells to the first outer surface of the carrier; (c) applying a force to the living cells to move the living cells into the holes; (d) observing or measuring at a first time a property of an individual living cell located at one of the holes of the carrier; and (e) observing or measuring at a second time a property of the same individual living cell which was observed or measured in step (d), the cell being located at the same hole of the carrier as in step (d).
Claim 5
Independent Claim
234 words
A method for placing individual living cells at identifiable addresses within the holes of a carrier comprising the steps of: (a) providing: a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; and means for holding the carrier so that the individual addresses of the holes in the carrier are identifiable by means of a set of x and y coordinates; (b) applying a fluid containing living cells to the first outer surface of the carrier; and (c) applying a force to the living cells to move the living cells into the holes.
Claim 6
Independent Claim
234 words
A method for placing individual living cells at identifiable addresses within the holes of a carrier comprising the steps of: (a) providing: a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; and means for holding the carrier so that the individual addresses of the holes in the carrier are identifiable by means of a set of x and y coordinates; (b) applying a fluid containing living cells to the first outer surface of the carrier; and (c) applying a force to the living cells to move the living cells into the holes.
Claim 7
Dependent Claim
28 words
The method of claim 1, 2, or 3 wherein the level of the second cross section is intermediate between the first and second outer surfaces of the carrier.
Claim 8
Dependent Claim
16 words
The method of claim 1, 2, or 3 wherein the holes are sized to contain lymphocytes.
Claim 9
Dependent Claim
27 words
The method of claim 1, 2, or 3 wherein the force in step (c) is produced by a pressure differential between said first and second outer surfaces.
Claim 10
Dependent Claim
30 words
The method of claim 1, 2, or 3 wherein the force in step (c) is produced by an electric field oriented perpendicular to the first outer surface of the carrier.
Claim 11
Dependent Claim
45 words
The method of claim 1, 2, or 3 wherein the force in step (c) is produced by an electric field parallel to the first outer surface of the carrier in conjunction with a crossed magnetic field parallel to the first outer surface of the carrier.
Claim 12
Dependent Claim
30 words
The method of claim 1, 2, or 3 further including a step after step (c) of washing the first outer surface of the carrier to remove excess cells or debris.
Claim 13
Dependent Claim
51 words
The method of claim 9 wherein the step of washing the first outer surface of the carrier is accompanied by a step of applying an electromagnetic force to the living cells and the ions in the fluid surrounding the living cells to enhance the rate of fluid exchange around the cells.
Claim 14
Dependent Claim
28 words
The method of claim 9 further including a subsequent step of adjusting the osmolarity of the fluid surrounding the cells so as to cause the cells to swell.
Claim 15
Dependent Claim
26 words
The method of claim 1, 2, or 3 further including a step after step (c) of applying a substance to the living cells on the carrier.
Claim 16
Dependent Claim
46 words
The method of claim 12 wherein the step of applying a substance is accompanied by a step of applying an electromagnetic force to the living cells and the ions in the fluid surrounding the living cells to enhance the rate of fluid exchange around the cells.
Claim 17
Dependent Claim
21 words
The method of claim 12 further including a subsequent step of observing the response of a living cell to the substance.
Claim 18
Dependent Claim
21 words
The method of claim 18 further including a subsequent step of removing the substance from the living cells on the carrier.
Claim 19
Dependent Claim
20 words
The method of claim 1, 2, or 3 further including a step of removing a living cell from a hole.
Claim 20
Dependent Claim
18 words
The method of claim 16 wherein the living cell is removed from a hole by an electromagnetic force.
Claim 21
Dependent Claim
41 words
The method of claim 17 wherein the living cell is removed from a hole by charging a probe and subjecting the living cell to the local electric field produced by he charged probe to move the cell out of the hole.
Claim 22
Dependent Claim
51 words
The method of claim 1, 2, or 3 further including a step of removing a group of living cells from their holes by charging an array of probes and subjecting the cells to the local electric fields produced by the array of probes to move the cells out of their holes.
Claim 23
Dependent Claim
28 words
The method of claim 1 further including a step of selecting living cells at specific positions on the carrier and multiplying those living cells to increase their number.
Claim 24
Dependent Claim
28 words
The method of claim 2 further including a step of selecting living cells at specific positions on the carrier and multiplying those living cells to increase their number.
Claim 25
Dependent Claim
28 words
The method of claim 3 further including a step of selecting living cells at specific addresses on the carrier and multiplying those living cells to increase their number.
Claim 26
Dependent Claim
21 words
The method of claim 20, 21 or 22 wherein the living cells are multiplied after having been removed from the carrier.
Claim 27
Dependent Claim
17 words
The method of claim 20, 21 or 22 wherein the living cells are multiplied on the carrier.
Claim 28
Dependent Claim
25 words
The method of claim 1 further including a step of selecting living cells at specific positions on the carrier and killing those selected living cells.
Claim 29
Dependent Claim
25 words
The method of claim 2 further including a step of selecting living cells at specific positions on the carrier and killing those selected living cells.
Claim 30
Dependent Claim
25 words
The method of claim 3 further including a step of selecting living cells at specific addresses on the carrier and killing those selected living cells.
Claim 31
Dependent Claim
29 words
The method of claim 25, 26, or 27 further including a subsequent step of multiplying the cells on the carrier which have not been killed to increase their number.
Claim 32
Dependent Claim
28 words
The method of claim 1 wherein the operation of moving the first living cell or moving the second living cell is performed by means of an electromagnetic force.
Claim 33
Dependent Claim
281 words
Apparatus for performing on a cell-by-cell basis one or more of the operations of (i) observing or measuring a property of a living cell, (ii) moving a living cell, or (iii) killing a living cell, comprising: (a) a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the positions on the carrier of the holes being identifiable and the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; (b) means for applying a fluid containing living cells to the first outer surface of the carrier; (c) means for applying a force to the living cells to move the living cells into the holes; and (d) means for performing on an individual living cell located in one of the holes in the carrier one or more of the operations of (i) observing or measuring a property of the living cell, (ii) moving the living cell, or (iii) killing the living cell.
Claim 34
Dependent Claim
281 words
Apparatus for performing on a cell-by-cell basis one or more of the operations of (i) observing or measuring a property of a living cell, (ii) moving a living cell, or (iii) killing a living cell, comprising: (a) a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the positions on the carrier of the holes being identifiable and the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; (b) means for applying a fluid containing living cells to the first outer surface of the carrier; (c) means for applying a force to the living cells to move the living cells into the holes; and (d) means for performing on an individual living cell located in one of the holes in the carrier one or more of the operations of (i) observing or measuring a property of the living cell, (ii) moving the living cell, or (iii) killing the living cell.
Claim 35
Dependent Claim
25 words
The apparatus of claim 30, wherein the level of the second cross section is intermediate between the first and second outer surfaces of the carrier.
Claim 36
Dependent Claim
13 words
The apparatus of claim 30, wherein the holes are sized to contain lymphocytes.
Claim 37
Dependent Claim
24 words
The apparatus of claim 30, wherein the carrier comprises a base made of a first material and a coating made of a second material.
Claim 38
Dependent Claim
17 words
The apparatus of claim 33 wherein the base is a conductor and the coating is a non-conductor.
Claim 39
Dependent Claim
17 words
The apparatus of claim 34 wherein the base is metal and the coating is an inorganic glass.
Claim 40
Dependent Claim
29 words
The apparatus of claim 34 wherein the base is metal and the coating is Si, SiO 2 , or a mixture of Si and Si 2 O 3 .
Claim 41
Dependent Claim
15 words
The apparatus of claim 36 wherein the base is metal and the coating is Si.
Claim 42
Dependent Claim
29 words
The apparatus of claim 30, wherein the carrier is made of metal and has a configuration which localizes electrolysis effects at points distant from the positions of the holes.
Claim 43
Dependent Claim
23 words
The apparatus of claim 38 wherein the carrier includes projections which extend away from the portion of the carrier which includes the holes.
Claim 44
Dependent Claim
275 words
Apparatus for selecting particular living cells from among other living cells comprising: (a) a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the addresses on the carrier of the holes being identifiable by means of a set of x and y coordinates, the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; (b) means for applying a fluid containing living cells to the first outer surface of the carrier; (c) means for applying a force to the living cells to move the living cells into the holes; (d) means for observing or measuring one or more properties of the living cells while the cells are in the holes; and (e) means associated with the means for observing or measuring for recording the addresses on the carrier of particular living cells based on the results of observing or measuring the one or more properties.
Claim 45
Dependent Claim
275 words
Apparatus for selecting particular living cells from among other living cells comprising: (a) a carrier defining first and second outer surfaces and comprising an ordered array of holes therethrough, the addresses on the carrier of the holes being identifiable by means of a set of x and y coordinates, the holes being sized to contain individual living cells therewithin in that the holes have (i) a first cross section at the first outer surface of the carrier of such dimensions that the living cell can pass through the first cross section without suffering substantial damage, (ii) a second cross section at a level spaced from the first outer surface of such dimensions that the living cell cannot pass through the second cross section, and (iii) a height between the first outer surface and the level of the second cross section such that either the entire living cell or substantially the entire living cell is contained within the hole so that the living cell is not washed out of the hole by the passage of a fluid across the first outer surface of the carrier; (b) means for applying a fluid containing living cells to the first outer surface of the carrier; (c) means for applying a force to the living cells to move the living cells into the holes; (d) means for observing or measuring one or more properties of the living cells while the cells are in the holes; and (e) means associated with the means for observing or measuring for recording the addresses on the carrier of particular living cells based on the results of observing or measuring the one or more properties.
Claim 46
Dependent Claim
95 words
The apparatus of claim 40 wherein the means for observing or measuring includes: (a) first structure means for supporting said carrier at a defined location thereon; (b) instrument means for observing or measuring the one or more properties; and (c) control means for controlling the relative locations of the instrument means and the carrier so that the instrument means is directed to a particular one of said holes in the carrier based on the address of the hole to observe or measure the one or more properties of a living cell located in the hole.
Claim 47
Dependent Claim
21 words
The apparatus of claim 41 wherein the instrument means comprises optical scanning means for determining optical properties of the living cells.
Claim 48
Dependent Claim
62 words
The apparatus of claim 41 wherein the first structure means includes means for supporting a plurality of carriers spaced-apart from one another, the spaced-apart carriers having living cells in the holes thereof, and wherein the apparatus includes second structure means positionable with respect to said first structure means for simultaneously applying a substance to the living cells on the plurality of carriers.
Claim 49
Dependent Claim
31 words
The apparatus of claim 43 wherein the second structure means includes means for applying the substance to the living cells from either the first or second outer surfaces of the carriers.
Claim 50
Dependent Claim
96 words
The apparatus of claim 4 wherein the first structure means includes means for supporting a plurality of carriers spaced-apart from one another, the spaced-apart carriers having living cells in the holes thereof, and wherein the apparatus includes second structure means positionable with respect to said first structure means for simultaneously applying first and second substances to the living cells, the first substance being applied to the living cells in a first carrier of the plurality of carriers and the second substance being applied to the living cells in a second carrier of the plurality of carriers.
Claim 51
Dependent Claim
42 words
The apparatus of claim 40 wherein the carrier includes force producing means for expelling any individual living cell from the hole in which it is located or for attracting any individual cell to a hole in which it is to be located.
Claim 52
Dependent Claim
23 words
The apparatus of claim 46 wherein the force producing means comprises electromagnetic means arranged in a predetermined pattern with respect to the holes.
References Cited (Backward Citations)
US1915568A
Cited
US2923669A
Cited
US2910406A
Cited
US3190827A
Cited
US3177945A
Cited
US3303254A
Cited
US3368963A
Cited
US3207684A
Cited
US3445152A
Cited
US3719583A
Cited
US3888770A
Cited
US3726597A
Cited
US3768914A
Cited
US4288330A
Cited
US3947121A
Cited
US3851972A
Cited
US3924947A
Cited
US4009435A
Cited
US3874851A
Cited
US4089765A
Cited
US4055799A
Cited
US4052163A
Cited
US3929583A
Cited
US4162850A
Cited
US4025306A
Cited
JPS5423993A
Cited
US4231660A
Cited
US4326934A
Cited
US4374644A
Cited
US4415405A
Cited
US4395397A
Cited
US4441972A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-03-08 | 1991-09-07 | 1992-03-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-03-08 | 1995-09-07 | 1996-03-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-03-08 | 1999-09-07 | 2000-03-08 | $7700.00 | Window Closed / Lapsed |