Interactive transparent individual cells biochip processor

• US 20070105089A1
• Filed: 12/28/2006
• Published: 05/10/2007
• Est. Priority Date: 10/25/2001
• Status: Abandoned Application

• Current Assignee: BAR ILAN University
• Original Assignee: BAR ILAN University
• Inventors: Deutsch, Mordechai
• Application Number:
  US11/646,317
• Publication Number:
  US 20070105089A1
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 3/5027 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 25/08 electrically charged
• CPC Class Codes: C12M 41/46 of cellular or enzymatic activity or functionality, e.g. cell viability
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/1475 using image analysis for extracting features of the particle
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1472 with colour
• CPC Class Codes: G01N 2015/1497 Particle shape
• CPC Class Codes: G01N 2035/00158 Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 2035/0429 Sample carriers adapted for special purposes
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G02B 21/34 Microscope slides, e.g. mounting specimens on microscope slides

Abstract

An Interactive Transparent Individual Cells Biochip Processor (ITICBP) device is described, which is useful for assessing a single, individual living cell at identifiable location or assessing group of cells each at identifiable location.

Claims

1. A chip-device for holding living cells, the device comprising a carrier having a plurality of individually addressable wells disposed on an upper surface each well configured to hold at least one living cell, and a lower surface, the device characterized in having at least one feature from amongst the four features:

(a) at least one of said wells is defined by an intersection of at least two channels on said upper surface;

(b) said carrier is provided with a transport channel configured to transport fluids from one location of said carrier to another location of said carrier;

(c) having at least one well microelectrode associated with at least one of said wells; and

(d) wherein said wells are juxtaposed.

2. The device of claim 1, wherein said wells are configured to hold no more than one living cell of a certain type.

3. The device of claim 1, wherein the dimensions of said wells are less than about 200 microns.

4. The device of claim 1, further comprising channels for transporting fluids from said upper surface to said lower surface through said carrier.

5. The device of claim 1, wherein said carrier is substantially transparent.

6. The device of claim 1, wherein said upper surface is substantially transparent and said lower surface is substantially not transparent.

7. The device of claim 1, wherein said lower surface is substantially transparent and said upper surface is substantially not transparent.

8. The device of claim 1, wherein at least one of said wells is defined by an intersection of at least two channels on said upper surface.

9. The device of claim 1, further comprising at least one transport channel on said upper surface configured to transport fluids from one location of said carrier to another location of said carrier.

10. The device of claim 1, wherein said wells are enclosures of dimensions such that substantially an entire cell of a certain type is containable within a said enclosure, each said enclosure having an opening at said upper surface, said opening defined by a first cross section of a size allowing passage of a cell of a certain size.

11. The device of claim 1, wherein said wells are juxtaposed.

12. The device of claim 11, having at least seven said wells, wherein the total interstitial area between said seven wells is less than or equal to about 0.35 the sum of the areas of said seven wells.

13. The device of claim 11, wherein said wells are hexagonally packed.

14. The device of claim 11, wherein a rim of a said well is substantially knife-edged.

15. The device of claim 11, further comprising at least one protuberance protruding from said upper surface between two adjacent wells.

16. The device of claim 1, further comprising at least one well microelectrode associated with a said well.

17. The device of claim 16, comprising a plurality of independently activatable well microelectrodes, each one of said plurality of well microelectrodes associated with a different said well

18. The device of claim 16, wherein said well microelectrode is transparent.

19. The device of claim 16, wherein said well microelectrode is configured to apply an electrical stimulus to a cell found within said associated well.

20. The device of claim 16, wherein said well microelectrode is configured to apply a repulsive force to a cell found within said associated well.

21. The device of claim 16, wherein said well microelectrode is configured to apply an attractive force to a cell found within said associated well.

22. The device of claim 16, wherein associated with at least one said well are at least two well microelectrodes.

23. The device of claim 22, wherein said two well microelectrodes are configured to simultaneously each apply a force on a cell found within said associated well so as to generate torque on said cell.

24. The device of claim 16, wherein said well microelectrode is a biosensor electrode.

25. The device of claim 1, further comprising at least one wall protruding from said upper surface, said at least one wall circumscribing at least one area of said upper surface where the points of the top edge of said wall define a plane.

26. The device of claim 1, further comprising a cover slip, said cover slip and said carrier configured so as to allow said cover slip to removeably rest above said upper surface substantially in parallel to said upper surface.

27. The device of claim 26, wherein said cover slip further comprises at least one cover slip microelectrode.

28. The device of claim 1, further comprising a flow generator, configured to generate a flow of fluid substantially parallel to said upper surface.

29. A method for rotating a living cell, comprising:

(a) providing at least two microelectrodes; and

(b) simultaneously applying a force from said at least two microelectrodes on the cell so as to generate torque on the cell.

30. A method for agitating a living cell, comprising repetitively:

(a) producing a first force having a first direction using a first microelectrode; and

(b) producing a second force having a second direction using a second microelectrode

wherein said second direction is substantially opposite said first direction.

31. A method for studying living cells, comprising:

(a) providing a group of cells;

(b) isolating cells from said group of cells each of said cells in an individual well, each said well being individually addressable;

(c) lysing at least one said isolated cell so that said lysates remain in said individual well; and

(d) examining said lysates.

32. A method for selecting cells, comprising:

(a) providing a group of cells;

(b) isolating cells from said group of cells each of said cells in an individual well, each said well provided with a force generator;

(c) examining each isolated cell; and

(d) selecting isolated cells fulfilling at least one criterion.