System and method for collecting data from individual cells

1. An automated system for loading individual cells from a population of cells in suspension into individual discrete locations within an array of individual discrete locations located in a cell carrier grid contained in a cell carrier grid holder, the system comprising:

(a) the cell carrier grid, the grid held in the cell carrier grid holder such that a lower surface of the grid is in communication with a space within the holder;

(b) the cell carrier grid holder, the holder comprising:

(i) said space in communication with said lower surface of the grid;

(ii) at least one port for introduction of a liquid into said space;

(iii) said at least one port further serving for removal of said liquid from said space;

(c) a vacuum source connectable to said port;

(d) at least one liquid reservoir for bringing at least one liquid into contact with the individual cells from a population of cells in suspension while the individual cells reside in the individual discrete locations; and

(e) a loading device facilitating communication between the grid holder containing the grid, said vacuum source, the population of cells in suspension, and said at least one liquid reservoir;

wherein application of vacuum via said port causes the individual cells from the population of cells in suspension to move into the individual discrete locations; and

wherein said at least one liquid may be applied to the individual cells from a location selected from the group consisting of said space and an upper surface of the cell carrier grid.

2. The system of claim 1, wherein said grid holder is constructed of at least one material selected from the group consisting of Lucite, plastic, and glass, silicon metal.

3. The system of claim 1, further comprising at least one robotic mechanism.

4. The system of claim 3, wherein said at least one robotic mechanism is designed and configured for performing at least one function selected from the group consisting of:

(i) placing the grid holder into said loading device;

(ii) removing the grid holder from said loading device

(iii) transferring the grid holder to a scanning assay device;

(iv) removing the grid holder from said scanning assay device.

5. The system of claim 3, wherein said robotic mechanism includes at least one item selected from the group consisting of at least one robotic arm, at least one conveyor belt, at least one pneumatic tube, at least one piston and at least one rotating plate.

6. The system of claim 1, wherein said port comprises a first port serving for introduction of a liquid into said space and a second port serving for removal of said liquid from said space.

7. The system of claim 1, further comprising a computerized control mechanism designed and configured to co-ordinate the actions of said vacuum source, the at least one population of cells in suspension, said loading device and said at least one liquid reservoir.

8. The system of claim 3, further comprising a computerized control mechanism designed and configured to co-ordinate the actions of said vacuum source, the at least one population of cells in suspension, said loading device, said at least one liquid reservoir, and said at least one robotic mechanism.

9. The system of claim 1, wherein at least one reagent contained within said at least one liquid is capable of imparting a measurable degree of fluorescence to the cells in the suspension at at least one wavelength.

10. The method of claim 9, wherein said at least one reagent capable of imparting a measurable degree of fluorescence is selected from the group consisting of:

(a) a substance that differentially stains living cells;

(b) a precursor of a fluorescent substance that differentially stains living cells;

(c) a fluorophore that stains nucleic acids; and

(d) a flourescently labeled antibody.

11. An automated method for loading individual cells from a population of cells in suspension into individual discrete locations within an array of individual discrete locations located in a cell carrier grid contained in a cell carrier grid holder, the method comprising the steps of:

(a) placing the grid holder into a loading device;

(b) automatically filling a space in the cell carrier grid holder with a liquid such that said liquid fills the individual discrete locations;

(c) automatically adding a portion of the cells in suspension to an upper surface of the grid; and

(d) automatically applying a force to said portion of the cells in suspension so that individual cells enter at least some of the individual discrete locations.

12. The method of claim 11, further comprising the step of:

(e) bringing the cells in the individual discrete locations into contact with at least one liquid.

13. The method of claim 11, wherein said step of placing the grid holder into a loading device is further automated.

14. The method of claim 11, wherein said grid holder is constructed of at least one material selected from the group consisting of Lucite, plastic, glass, silicon and metal.

15. The method of claim 11, wherein said step of placing the grid holder into said loading device is accomplished with the aid of at least one robotic mechanism.

16. The method of claim 11, wherein at least one additional step selected from the group consisting of:

(i) removing the grid holder from said loading device;

(ii) transferring the grid holder to a scanning assay device; and

(iii) removing the grid holder from said scanning assay device;

is performed by said at least one robotic mechanism which is further designed and configured for performing said at least one additional step.

17. The method of claim 15, wherein said robotic mechanism includes at least one item selected from the group consisting of at least one robotic arm, at least one conveyor belt, at least one pneumatic tube, at least one piston and at least one rotating plate.

18. The method of claim 16, wherein said robotic mechanism includes at least one item selected from the group consisting of at least one robotic arm, at least one conveyor belt, at least one pneumatic tube, at least one piston and at least one rotating plate.

19. The method of claim 11, wherein said steps of automatically filling a space, and automatically applying a force are accomplished by causing a liquid to flow through at least one port in said grid holder.

20. The method of claim 19, wherein causing said liquid to flow includes causing said liquid to flow through:

(i) a first port serving for introduction of said liquid into said space; and

(ii) a second port serving for removal of said liquid from said space.

21. The method of claim 11, wherein said steps of automatically filling a space, automatically adding a portion of the cells, and automatically applying a force are co-ordinated by a computerized control mechanism.

22. The method of claim 17, wherein said steps of automatically filling a space, automatically adding a portion of the cells, and automatically applying a force are co-ordinated by a computerized control mechanism which further controls said at least one robotic mechanism.

23. The method of claim 16, wherein said steps of automatically filling a space, automatically adding a portion of the cells, and automatically applying a force are co-ordinated by a computerized control mechanism which further controls said at least one robotic mechanism.

24. The method of claim 11, wherein at least one reagent contained within said liquid is capable of imparting a measurable degree of fluorescence to the cells in the suspension at at least one wavelength.

25. The method of claim 24, wherein said at least one reagent capable of imparting a measurable degree of fluorescence is selected from the group consisting of:

(a) a substance that differentially stains living cells;

(b) a precursor of a fluorescent substance that differentially stains living cells;

(c) a fluorophore that stains nucleic acids; and

(d) a flourescently labeled antibody.

26. An automated system useful for collection of data from a plurality of individual cells belonging to a population of cells in suspension, the system comprising:

(a) a cell carrier grid including a plurality of individual discrete locations arranged in an array such that each of said individual discrete locations is capable of engaging and retaining one of the individual cells, said grid held in a grid holder such that a lower surface of the grid is in communication with a space within said holder;

(b) said cell carrier grid holder comprising:

(i) said space in communication with said lower surface of the grid;

(ii) at least one port for introduction of a liquid into said space;

(iii) said at least one port further serving for removal of said liquid from said space;

(c) a vacuum source connectable to said port;

(d) at least one liquid reservoir for bringing at least one liquid into contact with the individual cells from the population of cells in suspension while the individual cells reside in the individual discrete locations; and

(e) a loading device facilitating communication between said grid holder containing said grid, said vacuum source, the population of cells in suspension, and said at least one liquid reservoir;

wherein application of vacuum via said port causes the individual cells from the population of cells in suspension to move into the individual discrete locations; and

wherein said at least one liquid may be applied to the individual cells from a location selected from the group consisting of said space and an upper surface of the cell carrier grid;

(f) an electro-optical scanner capable of illuminating the individual cells residing in said individual discrete locations and collecting at least a portion of photons emanating from the individual cells residing in said individual discrete locations; and

(g) a computerized control mechanism designed and configured to co-ordinate actions of said cell carrier grid holder, said vacuum source, the at least one population of cells in suspension, said at least one liquid reservoir, said loading device and said electro-optical scanner.

27. The system of claim 26, wherein said electro-optical scanner comprises:

(i) an optical unit, said optical unit comprising a camera, a light source, a photomultiplier, an optical shutter, and at least one optical filter; and

(ii) a scanning unit capable of exposing said discrete locations to light from said light source;

wherein said optical unit and components thereof and said scanning unit are controlled by said computerized control mechanism.

28. The system of claim 26, wherein said grid holder is constructed of at least one material selected from the group consisting of Lucite, plastic, glass, silicon and metal.

29. The system of claim 26, further comprising at least one robotic mechanism.

30. The system of claim 29, wherein said at least one robotic mechanism is designed and configured for performing at least one function selected from the group consisting of:

(i) placing the grid holder into said loading device;

(ii) removing the grid holder from said loading device

(iii) transferring the grid holder to a scanning assay device;

(iv) removing the grid holder from said scanning assay device.

31. The system of claim 29, wherein said robotic mechanism includes at least one item selected from the group consisting of at least one robotic arm, at least one conveyor belt, at least one pneumatic tube, at least one piston and at least one rotating plate.

32. The system of claim 26, wherein said port comprises a first port serving for introduction of a liquid into said space and a second port serving for removal of said liquid from said space.

33. The system of claim 26, wherein said electro-optical scanner further comprises a cell manipulation device selected from the group consisting of a micropipette, a needle, and an electrode;

wherein said control unit further co-ordinates actions of said cell manipulation device.

34. The system of claim 33, wherein said micropipette is capable of an action selected from the group consisting of removing at least a portion of an organelle from an individual cell, removing at least a portion of the individual cell's cytoplasm, and removing the individual cell from one of said discrete locations.

35. The system of claim 33, wherein said needle is capable of an action selected from the group consisting of injecting a substance into an individual cell residing in said discrete location and extracting a substance from an individual cell residing in said discrete location.

36. The system of claim 33, wherein said electrode is capable of an action selected from the group consisting of applying an electric current to an individual cell residing in said discrete location, measuring a potential difference across a membrane of an individual cell residing in said discrete location, and creating a potential difference across a membrane of an individual cell residing in said discrete location.

37. The system of claim 26, wherein at least one reagent contained within said at least one liquid is capable of imparting a measurable degree of fluorescence to the cells in the suspension at at least one wavelength.

38. The system of claim 37, wherein said at least one reagent capable of imparting a measurable degree of fluorescence is selected from the group consisting of:

(a) a substance that differentially stains living cells;

(b) a precursor of a fluorescent substance that differentially stains living cells;

(c) a fluorophore that stains nucleic acids; and

(d) a flourescently labeled antibody.

39. The system of claim 26, wherein said electro-optical scanner capable of collecting at least a portion of photons emanating from the individual cells residing in said individual discrete locations is further capable of gathering polarization data pertaining to said photons.

40. The system of claim 39, wherein said polarization data is useful in making a medical diagnosis.

41. An automated method of collection of data from a plurality of individual cells belonging to a population of cells in suspension, the method comprising the steps of:

(a) providing a cell carrier grid including a plurality of individual discrete locations arranged in an array such that each of said individual discrete locations is capable of engaging and retaining one of the individual cells, and holding said grid held in a grid holder such that a lower surface of the grid is in communication with a space within said holder;

(b) allowing at least one liquid to enter and leave said space in said grid holder via at least one port;

(c) causing the individual cells from the population of cells in suspension to move into the individual discrete locations by means of a vacuum source connectable to said port;

(d) supplying the population of cells in suspension;

(e) allowing communication between said at least one liquid in at least one liquid reservoir and the individual cells from the population of cells in suspension while the individual cells reside in said individual discrete locations wherein said at least one liquid may communicate with the individual cells from a location selected from the group consisting of said space and an upper surface of the cell carrier grid; and

(f) employing a loading device to facilitate communication between said grid holder containing said grid, said vacuum source, the population of cells in suspension, and said at least one liquid reservoir;

(g) illuminating the individual cells residing in said individual discrete locations and collecting at least a portion of photons emanating from the individual cells residing in said individual discrete locations by means of an electro-optical scanner; and

(h) co-ordinating actions of said cell carrier grid holder, said vacuum source, the population of cells in suspension, said at least one liquid reservoir, said loading device and said electro-optical scanner by means of a computerized control mechanism.

42. The method of claim 41, wherein said electro-optical scanner comprises:

(a) an optical unit, said optical unit comprising a camera, a light source, a photomultiplier, an optical shutter, and at least one optical filter; and

(b) a scanning unit capable of exposing said discrete locations to light from said light source;

wherein said optical unit and components thereof and said scanning unit are controlled by said computerized control mechanism.

43. The method of claim 41, wherein said grid holder is constructed of at least one material selected from the group consisting of Lucite, plastic, glass, silicon and metal.

44. The method of claim 41, comprising the additional step of providing at least one robotic mechanism.

45. The method of claim 44, wherein said at least one robotic mechanism performs at least one function selected from the group consisting of:

(i) placing said grid holder into said loading device;

(ii) removing said grid holder from said loading device

(iii) transferring said grid holder to a scanning assay device;

(iv) removing said grid holder from said scanning assay device.

46. The method of claim 44, wherein said robotic mechanism includes at least one item selected from the group consisting of at least one robotic arm, at least one conveyor belt, at least one pneumatic tube, at least one piston and at least one rotating plate.

47. The method of claim 41, wherein said at least one port comprises a first port serving for introduction of a liquid into said space and a second port serving for removal of said liquid from said space.

48. The method of claim 41, comprises the additional step of including within said electro-optical scanner a cell manipulation device selected from the group consisting of a micropipette, a needle, and an electrode;

wherein said control unit further co-ordinates actions of said cell manipulation device.

49. The method of claim 48, wherein said micropipette is capable of performing at least one step selected from the group consisting of removing at least a portion of an organelle from an individual cell, removing at least a portion of the individual cell's cytoplasm, and removing the individual cell from one of said discrete locations.

50. The method of claim 48, wherein said needle is capable of performing at least one step selected from the group consisting of injecting a substance into an individual cell residing in said discrete location and extracting a substance from an individual cell residing in said discrete location.

51. The method of claim 48, wherein said electrode is capable of performing at least one step selected from the group consisting of applying an electric current to an individual cell residing in said discrete location, measuring a potential difference across a membrane of an individual cell residing in said discrete location, and creating a potential difference across a membrane of an individual cell residing in said discrete location.

52. The method of claim 41, wherein at least one reagent contained within said at least one liquid is capable of imparting a measurable degree of fluorescence to the cells in the suspension at at least one wavelength.

53. The method of claim 52, wherein said at least one reagent capable of imparting a measurable degree of fluorescence is selected from the group consisting of:

(i) a substance that differentially stains living cells;

(ii) a precursor of a fluorescent substance that differentially stains living cells;

(iii) a fluorophore that stains nucleic acids; and

(iv) a flourescently labeled antibody.

54. The method of claim 41, wherein said step of illuminating the individual cells residing in said individual discrete locations and collecting at least a portion of photons emanating from the individual cells residing in said individual discrete locations further includes gathering polarization data pertaining to said photons.

55. The system of claim 54, wherein said polarization data is useful in making a medical diagnosis.

56. An article of manufacture useful for collection of data from a plurality of individual cells belonging to a population of cells in suspension in a clinical setting, the article of manufacture comprising:

(a) a cell carrier grid including a plurality of individual discrete locations arranged in an array such that each of said individual discrete locations is capable of engaging and retaining one of the individual cells, said grid held in a grid holder such that a lower surface of the grid is in communication with a space within said holder;

(b) said cell carrier grid holder comprising:

(i) said space in communication with said lower surface of the grid;

(ii) at least one port for introduction of a liquid into said space;

liquid from said space;

(c) a vacuum source connectable to said port;

(d) at least one liquid reservoir for bringing at least one liquid into contact with the individual cells from the population of cells in suspension while the individual cells reside in the individual discrete locations; and

(e) a loading device facilitating communication between said grid holder containing said grid, said vacuum source, the population of cells in suspension, and said at least one liquid reservoir;

wherein application of vacuum via said port causes the individual cells from the population of cells in suspension to move into the individual discrete locations; and

wherein said at least one liquid may be applied to the individual cells from a location selected from the group consisting of said space and an upper surface of the cell carrier grid.

(f) an electro-optical scanner capable of illuminating the individual cells residing in said individual discrete locations and collecting at least a portion of photons emanating from the individual cells residing in said individual discrete locations; and

(g) a computerized control mechanism designed and configured to co-ordinate actions of said cell carrier grid holder, said vacuum source, the population of cells in suspension, said at least one liquid reservoir, said loading device and said electro-optical scanner, said computerized control mechanism operable with a graphical user interface.

57. The article of manufacture of claim 56, further comprising instructions for performing specific analyses therewith, said instructions reducing the need for calibration thereof.

58. The article of manufacture of claim 56, further comprising a cell manipulation device.

59. An improved electro-optical scanner capable of individually collecting data from a plurality of individual cells residing in predefined locations, the scanner comprising:

(a) an optical unit, said optical unit comprising a camera, a light source, a photomultiplier, an optical shutter, and at least one optical filter;

(b) a cell carrier grid, said grid comprising an array of discrete locations, each of said discrete locations capable of engaging and retaining a single living cell;

(c) a scanning unit capable of exposing said discrete locations to light from said light source;

(d) a cell manipulation device selected from the group consisting of a micropipette, a needle, and an electrode and

(e) a control unit, said control unit comprising a computer designed and configured for co-ordinating actions of said optical unit, said cell carrier grid, said scanning unit and said cell manipulation device.

60. The electro-optical scanner of claim 59, wherein said micropipette is capable of an action selected from the group consisting of removing at least a portion of an organelle from an individual cell, removing at least a portion of the individual cell's cytoplasm, and removing the individual cell from one of said discrete locations.

61. The electro-optical scanner of claim 59, wherein said needle is capable of an action selected from the group consisting of injecting a substance into an individual cell residing in said discrete location and extracting a substance from an individual cell residing in said discrete location.

62. The electro-optical scanner of claim 59, wherein said electrode is capable of an action selected from the group consisting of applying an electric current to an individual cell residing in said discrete location, measuring a potential difference across a membrane of an individual cell residing in said discrete location, and creating a potential difference across a membrane of an individual cell residing in said discrete location.

63. A method of collecting data from individual cells belonging to a plurality of individual cells residing in predefined locations by means of an improved electro-optical scanner, the method comprising the steps of:

(a) causing individual cells from the plurality of individual cells to be engaged and retained in discrete locations belonging to an array of discrete locations in a cell carrier grid;

(b) exposing said discrete locations to light from a light source by employing a scanning unit;

(c) generating the data from an an optical unit, said optical unit comprising a camera, said light source, a photomultiplier, an optical shutter, and at least one optical filter;

(d) manipulating individual cells from the plurality of individual cells with a cell manipulation device selected from the group consisting of a micropipette, a needle, and an electrode; and

(e) co-ordinating actions of said optical unit, said cell carrier grid and said cell manipulation device and said scanning unit from a control unit, said control unit comprising a computer.

64. The method of claim 63, wherein said micropipette is capable of performing an additional step selected from the group consisting of removing at least a portion of an organelle from the individual cell, removing at least a portion of the individual cell's cytoplasm, and removing the individual cell from one of said discrete locations.

65. The method of claim 63, wherein said needle is capable of performing an additional step selected from the group consisting of injecting a substance into an individual cell residing in said discrete location and extracting a substance from an individual cell residing in said discrete location.

66. The method of claim 63, wherein said electrode is capable performing an additional step selected from the group consisting of applying an electric current to an individual cell residing in said discrete location, measuring a potential difference across a membrane of an individual cell residing in said discrete location, and creating a potential difference across a membrane of an individual cell residing in said discrete location.