1. A method of obtaining an optical lens from a polymerizable material, comprising:
providing a mold (1) that is formed of two facing and spaced shells (2, 3) and an annular seal (4) comprising means (10, 11) for cooperating with the periphery of said shells (2, 3) to define a molding cavity, said seal (4) being adapted to be compressed elastically when said shells (2, 3) are moved toward each other;
filling said molding cavity with said polymerizable material;
polymerizing the material filling the molding cavity;
prior to the polymerizing the material filling the molding cavity, applying an external mechanical force to move said shells toward each other; and
prior to the polymerizing, releasing said force, the force producing a compression of the seal (4) and the shells (2, 3), wherein
a filling hole (19) is provided in said annular seal (4), away from said means (10, 11) for cooperating with the periphery of the shells (2, 3), in that during said filling stage said material is introduced into the cavity through said filling hole (19), and in that said material is introduced after said step of applying a mechanical external force to move said shells toward each other and before said step of releasing said force,
wherein a plug (5) is provided for plugging said filling hole (19) in said seal (4) and said filling step comprises, after introducing said material and before said step of releasing said force, a step of plugging said filling hole (19) with said plug (5),
the only hole in said annular seal (4) is said filling hole (19), and
said filling hole comprises a first section (21) and a second section (22), the first section (21) extending between a first end opening into said molding cavity and a second end at which it is joined to a first end of said second section (22), in that said plug (5) is provided for plugging said filling hole and comprises a body (25) having a first portion adapted to fit tightly into said first section (21) of the filling hole (19) to plug the filling hole (19), and the body (25) of the plug (5) has a second portion to define with said second section (22) of the filling hole (19) a chamber (26) around said second portion of the body (25), with said first portion of the body (25) having a free end, and in that said cavity and said first section (21) of the hole (19) are filled during said step of introducing the polymerizable material into the cavity.
2. The method according to claim 1, wherein said molding cavity and said first section (21) of the filling hole (19) are filled during said filling step to the level of the junction between the first section (21) and the second section (22).
3. The method according to claim 2, wherein the volume of said chamber (26) around the body (25) of the plug (5) is greater than the volume of said first section (21) of the filling hole (19).
4. The method according to claim 1, wherein said filling hole (19) further comprises a third section (23) that extends between a first end at which it is joined to the second end of the second section (22) and a second end that opens to the exterior of said seal (4), and in that said plug (5) comprises a head (24) adapted to fit tightly into said third section (23) of the filling hole (19) to plug it, so that said chamber (26) is then entirely closed.
5. The method according to claim 1, wherein a boss (20) is provided around said filling hole (19) and projects relative to the lateral surface (15) of the seal (4).
6. The method according to claim 1, wherein said filling hole (19) is oriented in a radial direction.
7. The method according to claim 1, wherein said filling hole (19) is halfway or substantially halfway between said means (10, 11) adapted to cooperate with a first shell (2) and with the second shell (3), respectively.
8. The method according to claim 1, wherein said step of applying a mechanical external force to move said shells toward each other is adapted to move said shells toward each other until a predetermined force is reached.
9. The method according to claim 8, wherein said force to move said shells toward each other is produced by an actuator (37) connected to a control center (40).
10. The method according to claim 8, wherein, during said step of applying a force to move said shells toward each other, said force is applied to said shells by way of respective sleeves (34, 35) having a diameter slightly less than that of said shells (2, 3).
11. The method according to claim 1, wherein a unit (31) is provided for receiving said mold (1) and in that said step of applying a force to move said shells toward each other and said step of releasing said force are effected by means of said receiving unit (31).
12. The method according to claim 11, wherein centering means (32) and angular positioning means (33) are provided in said unit (31) for receiving the mold (1).
13. The method according to claim 12, wherein said centering means comprise two fingers (32) oriented longitudinally and adapted to cooperate with the lateral surface (15) of said seal (4) and said angular positioning means comprise a fork (33) adapted to cooperate with a boss (20) projecting relative to the lateral surface (15) of said seal.
14. The method according to claim 11, wherein, for effecting said filling step, there are provided a station (41) for introducing said polymerizable material into the cavity of said mold (1) and a station (42) for plugging said filling hole, said introduction station (41) and said plugging station (42) being disposed side by side, and in that said unit (31) for receiving the mold (1) is movable between a first position in which it is vertically aligned with the plugging station (42) and a second position in which it is vertically aligned with the introduction station (41).
15. The method according to claim 1, wherein said step of introducing the polymerizable material is effected by means of a station (41) that comprises a nozzle (48) for introducing said material and a nozzle (49) for aspirating surplus material.
16. The method according to claim 15, wherein said nozzle (48) for introducing said material is inclined.
17. The method according to claim 15, wherein the distal end of said nozzle (48) for introducing said material is below the distal end of said aspiration nozzle (49).
18. The method according to claim 1, wherein the plug (5) is provided for plugging said filling hole (19) and comprises a blind hole (51) and in that a step of plugging said filling hole with said plug is effected at a plugging station (42) comprising a canula (50) adapted to be engaged in said blind hole (51) of said plug (5).
19. The method according to claim 18, wherein said canula (50) is connected to a vacuum system to hold said plug in place on said canula and said canula (50) is vented to the atmosphere to release said plug (5).
20. The method according to claim 18, wherein said plug (5) is pressed into said filling hole (19) by driving said plugging station (42).
21. The method according to claim 1, wherein there is provided a relatively narrow lug (17) projecting relative to the lateral surface (15) of said seal (4) and having a transverse end surface (18) incorporating a predetermined location relative to the remainder of the seal.
22. The method according to claim 21, wherein, for effecting said filling step, there are provided a station (41) for introducing said polymerizable material into the cavity of said mold (1) and a station (42) for plugging said filling hole (19), said introduction station (41) and said plugging station (42) being disposed side by side, in that a unit (31) is provided for receiving said mold (1) in a predetermined position and said receiving unit (31) is mobile between a first position in which it is vertically aligned with the plugging station (42) and a second position in which it is vertically aligned with the introduction station (41).
23. The method according to claim 22, wherein at least one optical cell (46, 47) is provided for detecting the position of the mold (1) relative to said filling station (41) or said plugging station (42) and in that said unit (31) for receiving the mold is placed in vertical alignment with said filling station (41) or in vertical alignment with said plugging station (42) in conjunction with said optical cell (46, 47).
24. The method according to claim 23, wherein respective optical cells (46, 47) are provided for said filling station (41) and said plugging station (42).
25. An annular seal, comprising:
means (10, 11) for cooperating with a periphery of two facing first and second molding shells (2, 3) to define a molding cavity, adapted to be compressed elastically by a force for moving the shells toward each other that is applied between the means (10, 11) adapted to cooperate with the periphery of the first shell (2) and the means (10, 11) adapted to cooperate with the periphery of the second shell (3);
a filling hole (19) away from said means (10, 11) and adapted to cooperate with the periphery of the shells (2, 3), the filling hole comprising a first section (21) and a second section (22), the first section (21) extending between a first end opening into said molding cavity and a second end by which it is joined to a first end of the second section (22),
the only hole in said seal is said filling hole (19), and
a plug (5) comprising a body (25) having a first portion adapted to fit tightly into said first section (21) of the filling hole (19) to plug it and a second portion to define with said second section (22) of the filling hole (19) a chamber (26) around said body (25) of the plug, with said first portion of the body (25) having a free end,
wherein the annular seal is adapted for obtaining an optical lens from a polymerizable material by:
filling said molding cavity with said polymerizable material by a filling means(41, 42);
polymerizing the material filling the molding cavity;
prior to the polymerizing the material filling the molding cavity, applying an external mechanical force to move said shells toward each other by a means(34-40) for applying a force; and
prior to the polymerizing, releasing said force, the force producing a compression of the seal (4) and the shells (2, 3), wherein
in that during said filling stage said material is introduced into the cavity through said filling hole (19), and in that said material is introduced after said step of applying the external mechanical force to move said shells (2, 3) toward each other before said step of releasing said force.
26. The seal according to claim 25, wherein a the volume of said chamber (26) around the body (25) of the plug (5) is greater than a volume of said first section (21) of the filling hole (19).
27. The seal according to claim 25, wherein said filling hole (19) further comprises a third section (23) that extends between a first end at which it is joined to the second end of the second section (22) and a second end that opens to the exterior of said seal (4) and in that said plug (5) comprises a head (24) adapted to fit tightly into said third section (23) of the filling hole (19) to plug it so that said chamber (26) is then entirely closed.
28. The seal according to claim 25, wherein the seal further comprises a boss (20) around said filling hole (19) and projecting relative to its lateral surface (15).
29. The seal according to claim 25, wherein said filling hole (19) is oriented in a radial direction.
30. The seal according to claim 25, wherein said filling hole (19) is halfway or substantially halfway between said means (10, 11) adapted to cooperate with a first shell (2) and with the second shell (3), respectively.
31. The seal according to claim 25, wherein the seal further comprises a relatively narrow lug (17) projecting relative to the lateral surface (15) of said seal (4) and having a transverse edge surface (18) at a predetermined location relative to the remainder of the seal.
32. The seal according to claim 31, wherein an the angular distance between said filling hole (19) and said relatively narrow lug (17) is such that said lug (17) is visible above said seal (14) when said mold (1) is placed with said filling hole (19) at the top.
33. The seal according to claim 25, wherein said plug (5) for plugging said filling hole (19) comprises a blind hole (51) having its closed end inside said body (25).
34. The seal according to claim 25, wherein the seal further comprises a belt (8) to the inside of which is joined a bead (9) narrower than said belt (8), said bead (9) having a dovetail-shaped cross section whose narrower side is that by which said bead (9) is joined to said belt (8), so that there exists on either side of said bead (9) a recess adapted to receive one of said shells (2, 3).
35. The seal according to claim 25, wherein said plug (5) and said seal (4) are made from the same material.
36. A device for obtaining an optical lens from a polymerizable material, the device comprising:
a mold (1) formed of two facing and spaced molding shells (2, 3); and
an annular seal (4) comprising means (10, 11) for cooperating with the periphery of said shells (2, 3) to define a molding cavity, said seal (4) being adapted to be, prior to polymerizing said polymerizable material filling the molding cavity, compressed elastically by a force for moving said shells toward each other to produce a compression of the seal (4) providing a seal between the seal (4) and the shells (2, 3); and
means (41, 42) for filling said molding cavity with said polymerizable material and means (34-40) for applying a force for moving said shells (2, 3) toward each other, wherein
said seal (4) comprises a filling hole (19) away from said means (10, 11) for cooperating with a periphery of the shells (2, 3), in that said filling means (41, 42) are adapted to introduce said material into the molding cavity through said filling hole (19), and in that said means (34-40) applying a force for moving said shells toward each other are adapted to apply and release said force respectively before and after the use of said filling means (41, 42), wherein
the device adapted for obtaining the optical lens from the polymerizable material by:
filling said molding cavity with said polymerizable material;
polymerizing the material filling the molding cavity;
prior to the polymerizing the material filling the molding cavity, applying the force to move said shells toward each other; and
prior to the polymerizing, releasing said force, the force producing the compression of the seal (4) and the shells (2, 3), wherein
in that during said filling stage said material is introduced into the cavity through said filling hole (19), and in that said material is introduced after said step of applying the force to move said shells toward each other before said step of releasing said force, and wherein
the filling hole comprises a first section (21) and a second section (22), the first section (21) extending between a first end opening into said molding cavity and a second end by which it is joined to a first end of the second section (22); said seal (4) further comprising a plug (5) having a body (25) with a first portion adapted to fit tightly into said first section (21) of the filling hole (19) to plug the filling hole (19), and the body (25) has a second portion to define with the second section (22) of the filling hole (19) a chamber (26) around said second portion of the body (25), with said first portion of the body (25) having a free end.
37. The device according to claim 36, wherein said means (34-40) for applying a force for moving said shells (2, 3) toward each other comprise means (37, 40) for moving said shells toward each other until a predetermined force is reached.
38. The device according to claim 37, wherein said means for applying a force for moving said shells toward each other comprise an actuator (37) connected to a control center (40).
39. The device according to claim 36, wherein said means for applying a force for moving said shells toward each other comprise, for applying said force to said shell, respective sleeves (34, 35) whose diameter is slightly less than that of said shells (2, 3).
40. The device according to claim 36, wherein the device further comprises a unit (31) for receiving said mold (1) provided with said means (34-40) for applying a force for moving said shells toward each other.
41. The device according to claim 40, wherein said unit (31) for receiving the mold (1) comprises centering means (32) and angular positioning means (33).
42. The device according to claim 41, wherein said centering means comprise two longitudinally oriented fingers (32) adapted to cooperate with the lateral surface (15) of said seal (4) and said angular positioning means comprise a fork (33) adapted to cooperate with a boss (20) projecting relative to the lateral surface (15) of said seal.
43. The device according to claim 36, wherein said filling means comprise a station (41) for introducing said polymerizable material into the cavity of said mold (1) and a station (42) for plugging said filling hole, said introduction station (41) and said plugging station (42) being disposed side by side, in that said device (30) comprises a unit (31) for receiving said mold in a vertical position with said filling hole (19) situated at the top of said seal (4), and in that said unit (31) for receiving the mold (1) is movable between a first position in which it is vertically aligned with the plugging station (42) and a second position in which it is vertically aligned with the introduction station (41).
44. The device according to claim 43, wherein said introduction station (41) comprises a nozzle (48) for introducing said material and a nozzle (49) for aspirating surplus material.
45. The device according to claim 44, wherein said material introduction nozzle (48) is inclined.
46. The device according to claim 44, wherein a the distal end of said introduction nozzle (48) is below a distal end of said aspiration nozzle (49).
47. The device according to claim 44, wherein said plug (5) for plugging said filling hole (19) comprises a blind hole (51) and in that said plugging station (42) comprises a canula (50) adapted to be engaged in said blind hole (51) of said plug (5).
48. The device according to claim 47, wherein the device further comprises means for connecting said canula (50) to a vacuum system to hold said plug in place on said canula and for venting said canula (50) to the atmosphere to release said plug (5).
49. The device according to claim 47, wherein the device further comprises means for driving said plugging station (42) to push said plug (5) into said filling hole (19).
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A nanoscale nucleic acid sequence detection apparatus comprising:
a) a hydrophilic nonconductive substrate serving as a sample plate;
b) a cathode macroelectrode located on one surface of said substrate;
c) an anode macroelectrode located on said surface of said substrate such that the spacing between said cathode macroelectrode and said anode macroelectrode is greater than the length of one nucleic acid molecule, the spacing between said cathode macroelectrode and said anode macroelectrode defining a nucleic acid loading and delivery path;
d) a molecular transport liquid located on said surface of said substrate;
e) an injection device capable of introducing a sample nucleic acid molecule into said molecular transport liquid;
f) a programmable pulse generator connected to said cathode macroelectrode and said anode macroelectrode, said programmable pulse generator capable of controllably moving a nucleic acid molecule contained in said liquid along the nucleic acid loading and delivery path between said cathode macroelectrode and said anode macroelectrode by means of a programmable electrophoresis electric field;
g) a first nanoelectrode located on said surface of said substrate;
h) a second nanoelectrode located on said surface of said substrate such that the gap between said first nanoelectrode and said second nanoelectrode crosses the nucleic acid loading and delivery path, the gap between said first nanoelectrode and said second nanoelectrode defining a nanometer-size nucleic acid detection gate on said hydrophilic nonconductive substrate;
i) a first nonhydrophilic and nonconductive protective insulating shield constructed on said surface of said substrate along the sides of said first nanoelectrode, the construction of said first protective insulating shield such that only a tip of said first nanoelectrode remains exposed on said surface of said substrate;
j) a second nonhydrophilic and nonconductive protective insulating shield constructed on said surface of said substrate along the sides of said second nanoelectrode, the construction of said second protective insulating shield such that only a tip of said second nanoelectrode remains exposed on said surface of said substrate; and
k) a nucleic acid nucleotide base detection means located at said nucleic acid detection gate.
2. The apparatus of claim 1, further comprising:
two parallel spaced-apart electrically conductive plates, said plates arranged such that said sample plate is located between said electrically conductive plates; and
a second programmable pulse generator connected to said electrically conductive plates, said second programmable pulse generator capable of applying a holding electric field across said conductive plates in order to orient the nucleic acid molecule contained in said liquid with respect to said sample plate and said conductive plates.
3. The apparatus of claim 1 wherein said injection device is a micropipette, a microfluidic injection device, or a nanofluidic injection device.
4. The apparatus of claim 2 wherein the movement and orientation of a sample nucleic acid molecule is precisely controlled by coordinated action of said programmable electrophoresis electric field and said holding electric field.
5. The apparatus of claim 1 wherein the moving direction and step size of a sample nucleic acid molecule at said detection gate is controlled by adjusting the direction, amplitude, and duration of the programmable electrophoresis electric field.
6. The apparatus of claim 2 wherein a sample nucleic acid molecule is oriented with its negatively charged chain of phosphate groups pointing downward toward the surface of the sample plate, and its nucleotide bases pointing upward as desired for detection by using the holding electric field at the proper strength and in the correct direction, i.e., the electrically conductive plate beneath the sample plate positively charged.
7. The apparatus of claim 2 wherein a sample nucleic acid molecule is held at said detection gate for a period by a holding electric pulse from said second programmable pulse generator delivered through said parallel electrically conductive plates so as to ensure reliable detection of the nucleotides.
8. The apparatus of claim 1 wherein the passage of a single nucleic acid molecule is achieved by use of detection gate spacing in the range of 1-10 nm.
9. The apparatus of claim 1 wherein the passage of a single nucleic acid molecule is achieved by use of detection gate spacing in the range of 2-6 nm.
10. The apparatus of claim 1 wherein the detection of a single nucleic acid molecule and reading of its nucleotide base sequence is achieved by use of a detection gate spacing in the range of 1-10 nm.
11. The apparatus of claim 1 wherein the detection of a single nucleic acid molecule and reading of its nucleotide base sequence is achieved by use of a detection gate spacing in the range of 2-6 nm.
12. The apparatus of claim 1 wherein said molecular transport liquid is provided and controlled by a relative humidity control system.
13. The apparatus of claim 1 further comprising a hydrophilic and nonconductive cover placed on the top sides of said macroelectrodes, said nanoelectrodes, and said protective shields to control the thickness of said molecular transport liquid on said hydrophilic nonconductive substrate.
14. The apparatus of claim 1 wherein said nucleic acid nucleotide base detection means is a tunneling current detector.
15. The apparatus of claim 1 wherein said nucleic acid nucleotide base detection means is a tunneling current spectroscope.
16. The apparatus of claim 1 wherein said nucleic acid nucleotide base detection means is a dielectric molecular detector.
17. The apparatus of claim 1 wherein said nucleic acid nucleotide base detection means is a high-resolution atomic force microscopic (AFM) probe.
18. The apparatus of claim 1 wherein said nucleic acid nucleotide base detection means is an electrostatic force microscopic (EFM) probe.
19. The apparatus of claim 1 wherein said molecular transport liquid is a chemical solution.
20. The apparatus of claim 1 wherein the passage of a single nucleic acid molecule and detection of its nucleotides is enhanced by use of appropriate solvent conditions such as pH and ionic strengths.
21. The apparatus of claim 2 wherein the actions of said nucleic acid nucleotide base detection and said electrophoresis and holding electric fields are coordinated and synchronized.
22. The apparatus of claim 1 wherein the apparatus is calibrated with standard nucleic acid samples of known sequences, and signal profiles of said sequences are established for each of the four distinct nucleotide bases: adenine (A), guanine (G), thymine (T) (uracil (U) if RNA), and cytosine (C).
23. The apparatus of claim 22 wherein the nucleotide sequence information of an unknown nucleic acid sample molecule is obtained by comparing its nucleotide base detection signals with said established signal profiles of said four distinct nucleotides with computer-assisted data fitting.
24. A nanoscale nucleic acid sequence detection apparatus comprising:
a) a hydrophobic and nonconductive substrate serving as a sample plate;
b) a cathode macroelectrode located on one surface of said substrate;
c) an anode macroelectrode located on said surface of said substrate such that the spacing between said cathode macroelectrode and said anode macroelectrode is greater than the length of one nucleic acid molecule, the spacing between said cathode macroelectrode and said anode macroelectrode defining a nucleic acid loading and delivery path;
d) a first nanoelectrode located on said surface of said substrate;
e) a second nanoelectrode located on said surface of said substrate such that the gap between said first nanoelectrode and said second nanoelectrode crosses the nucleic acid loading and delivery path, the gap between said first nanoelectrode and said second nanoelectrode defining a nanometer-size nucleic acid detection gate on said hydrophobic and nonconductive substrate;
f) a hydrophilic sample loading and delivery area on said hydrophobic and nonconductive substrate, said hydrophilic area extending along said nucleic acid loading and delivery path from said cathode macroelectrode to said anode macroelectrode, said hydrophilic sample loading and delivery area constructed so as to taper gradually less from said cathode macroelectrode to said nucleic acid detection gate;
g) a molecular transport liquid located on said hydrophilic sample loading and delivery area, said molecular transport liquid preferentially tending to form a funnel liquid delivery path on said hydrophilic sample loading and delivery area;
h) an injection device capable of introducing a sample nucleic acid molecule into said molecular transport liquid;
i) a nucleic acid nucleotide base detection means located at said nucleic acid detection gate;
j) a first programmable pulse generator connected to said cathode macroelectrode and to said anode macroelectrode, said first programmable pulse generator capable of controllably moving a nucleic acid molecule contained in said liquid along the nucleic acid loading and delivery path between said cathode macroelectrode and said anode macroelectrode by means of a programmable electrophoresis electric field;
k) two parallel spaced-apart electrically conductive plates, said electrically conductive plates arranged such that said sample plate is located between said electrically conductive plates; and
l) a second programmable pulse generator connected to said electrically conductive plates, said second programmable pulse generator capable of applying a holding electric field across said electrically conductive plates in order to orient the nucleic acid molecule contained in said liquid with respect to said sample plate and said electrically conductive plates.
25. The apparatus of claim 24 wherein said injection device is a micropipette, a microfluidic injection device, or a nanofluidic injection device.
26. The apparatus of claim 24 wherein the movement and orientation of a sample nucleic acid molecule is precisely controlled by coordinated action of said programmable electrophoresis electric field and said holding electric field.
27. The apparatus of claim 24 wherein the moving direction and step size of a sample nucleic acid molecule at said detection gate is controlled by adjusting the direction, amplitude, and duration of the programmable electrophoresis electric field.
28. The apparatus of claim 24 wherein a sample nucleic acid molecule is oriented with its negatively charged chain of phosphate groups pointing downward toward the surface of the sample plate, and its nucleotide bases pointing upward as desired for detection by using the holding electric field in the proper strength and in the correct direction, i.e., the electrically conductive plate beneath the sample plate positively charged.
29. The apparatus of claim 24 wherein a sample nucleic acid molecule is held at said detection gate for a period by a holding electric pulse from said second programmable pulse generator delivered through said parallel electrically conductive plates so as to ensure reliable detection of the nucleotides.
30. The apparatus of claim 24 wherein the passage of a single nucleic acid molecule is achieved by use of detection gate spacing in the range of 1-10 nm.
31. The apparatus of claim 24 wherein the passage of a single nucleic acid molecule is achieved by use of detection gate spacing in the range of 2-6 nm.
32. The apparatus of claim 24 wherein the detection of a single nucleic acid molecule and reading of its nucleotide base sequence is achieved by use of a detection gate spacing in the range of 1-10 nm.
33. The apparatus of claim 24 wherein the detection of a single nucleic acid molecule and reading of its nucleotide base sequence is achieved by use of a detection gate spacing in the range of 2-6 nm.
34. The apparatus of claim 24 wherein said molecular transport liquid is provided and controlled by a relative humidity control system.
35. The apparatus of claim 24 wherein said nucleic acid nucleotide base detection means is a tunneling current detector.
36. The apparatus of claim 24 wherein said nucleic acid nucleotide base detection means is a tunneling current spectroscope.
37. The apparatus of claim 24 wherein said nucleic acid nucleotide base detection means is a dielectric molecular detector.
38. The apparatus of claim 24 wherein said nucleic acid nucleotide base detection means is a high-resolution atomic force microscopic (AFM) probe.
39. The apparatus of claim 24 wherein said nucleic acid nucleotide base detection means is an electrostatic force microscopic (EFM) probe.
40. The apparatus of claim 24 wherein said molecular transport liquid is a chemical solution.
41. The apparatus of claim 24 wherein the passage of a single nucleic acid molecule and detection of its nucleotides is enhanced by use of appropriate solvent conditions such as pH and ionic strengths.
42. The apparatus of claim 24 wherein the actions of said nucleic acid nucleotide base detection and said electrophoresis and holding electric fields are coordinated and synchronized.
43. The apparatus of claim 24 wherein the apparatus is calibrated with standard nucleic acid samples of known sequences, and signal profiles of said sequences are established for each of the four distinct nucleotide bases: adenine (A), guanine (G), thymine (T) (uracil (U) if RNA), and cytosine (C).
44. The apparatus of claim 43 wherein the nucleotide sequence information of an unknown nucleic acid sample molecule is obtained by comparing its nucleotide base detection signals with said established signal profiles of said four distinct nucleotides with computer-assisted data fitting.