Multiple capillary biochemical analyzer
First Claim
1. An analyzer for analyzing an organic sample, the analyzer comprising:
- a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample;
a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity;
means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes;
an electrophoretic voltage source connected across said capillary tubes to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes, said flow chamber being held essentially at ground potential;
a detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes; and
an outlet for draining said sheath flow fluid and entrained streams directly from said flow chamber to waste, said outlet having a substantially larger flow area than said capillary tubes to thereby permit non-capillary flow therethrough.
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Accused Products
Abstract
A multiple capillary analyzer allows detection of light from multiple capillaries with a reduced number of interfaces through which light must pass in detecting light emitted from a sample being analyzed, using a modified sheath flow cuvette. A linear or rectangular array of capillaries is introduced into a rectangular flow chamber. Sheath fluid draws individual sample streams through the cuvette. The capillaries are closely and evenly spaced and held by a transparent retainer in a fixed position in relation to an optical detection system. Collimated sample excitation radiation is applied simultaneously across the ends of the capillaries in the retainer. Light emitted from the excited sample is detected by the optical detection system. The retainer is provided by a transparent chamber having inward slanting end walls. The capillaries are wedged into the chamber. One sideways dimension of the chamber is equal to the diameter of the capillaries and one end to end dimension varies from, at the top of the chamber, slightly greater than the sum of the diameters of the capillaries to, at the bottom of the chamber, slightly smaller than the sum of the diameters of the capillaries. The optical system utilizes optic fibres to deliver light to individual photodetectors, one for each capillary tube. A filter or wavelength division demultiplexer may be used for isolating fluorescence at particular bands.
224 Citations
63 Claims
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1. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; an electrophoretic voltage source connected across said capillary tubes to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes, said flow chamber being held essentially at ground potential; a detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes; and an outlet for draining said sheath flow fluid and entrained streams directly from said flow chamber to waste, said outlet having a substantially larger flow area than said capillary tubes to thereby permit non-capillary flow therethrough. - View Dependent Claims (13, 14, 52, 53)
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2. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; an electrophoretic voltage source to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes;
said electrophoretic voltage source being connected across the length of the capillary tubes whereby said flow chamber is held essentially at ground potential; anda detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes.
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3. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; a detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes; an exit port in said flow chamber for draining said sheath flow fluid and entrained streams directly from said flow chamber to waste, said exit port having a substantially larger flow area than said capillary tubes to thereby permit non-capillary flow therethrough; and means to prevent drop formation at said exit port. - View Dependent Claims (33)
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4. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes;
said means including an electrophoretic voltage source connected across the length of the capillary tubes;a detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes; an exit port in said flow chamber for drawing sheath fluid from said chamber; and means to prevent drop formation at said exit port.
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5. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; a detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes, said detector being selected from the group comprising thermo-optical absorption detectors and electrochemical detectors; and an outlet for draining said sheath flow fluid and entrained streams directly from said flow chamber to waste, said outlet having a substantially larger flow area than said capillary tubes to thereby permit non-capillary flow therethrough.
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6. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes;
said means including an electrophoretic voltage source connected across the length of the capillary tubes; anda detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes, said detector being selected from the group comprising thermo-optical absorption detectors and electrochemical detectors.
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7. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes, said means to force being selected from the group comprising pumps and gas pressure; a detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes; and an outlet for draining said sheath flow fluid and entrained streams directly from said flow chamber to waste, said outlet having a flow area substantially larger than that of the capillary tubes to thereby permit non-capillary flow therethrough.
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8. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; a detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes; an outlet for draining said sheath flow fluid and entrained streams directly from said flow chamber to waste, said outlet having a flow area substantially larger than that of the capillary tubes to thereby permit non-capillary flow therethrough; and wherein said plurality of capillary tubes is arranged in a two-dimensional array and wherein said detector comprises a mass spectrometer having an ionization chamber, the second ends of said capillary tubes being disposed within said ionization chamber.
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9. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes;
said means including an electrophoretic voltage source connected across the length of the capillary tubes;a detector positioned to detect organic sample in the individual sample streams emerging from the capillary tubes; and wherein said plurality of capillary tubes is arranged in a two-dimensional array and wherein said detector comprises a mass spectrometer having an ionization chamber, the second ends of said capillary tubes being disposed within said ionization chamber.
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10. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent to and abutting each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the second ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that organic sample from the capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; and a detector to detect organic sample emerging in the individual sample streams from the capillary tubes. - View Dependent Claims (11, 12, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 61, 62)
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45. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source a flow chamber having an interior cavity, the seconds ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force said organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; and a detector, including a source of collimated electromagnetic radiation having a wavelength that may excite the sample to emit radiation to detect organic sample emerging in the individual sample streams from the capillary tubes;
said source being aligned to provide collimated light through the organic sample drawn from the capillary tubes by the sheath fluid, said detector further comprising an optical system aligned to receive emitted radiation from the organic sample, said optical system including plural photodetectors, one for each capillary tube. - View Dependent Claims (51, 54)
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46. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the second ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force the organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; and a detector including a first source of collimated electromagnetic radiation having a wavelength that may excite the sample to emit radiation to detect organic sample emerging in the individual sample streams from the capillary tubes, said source being aligned to provide collimated light through organic sample drawn from the capillary tubes by the sheath fluid, said detector further comprising a second source of collimated electromagnetic radiation aligned to direct a beam of radiation at each of said sample streams, further comprising an optical system aligned to detect radiation from said sample streams.
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47. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the second ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in said capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force the organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; a detector including a source of collimated electromagnetic radiation having a wavelength that may excite the sample to emit radiation to detect organic sample emerging in the individual sample streams from the capillary tubes;
said source being aligned to provide collimated light through the organic sample drawn from the capillary tubes by the sheath fluid; andwherein the means to force sample through the capillary tubes comprises a pump and the capillary tubes are filled with chromatographic packing material.
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48. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the second ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in the capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; a detector to detect organic sample emerging in the individual sample streams from the capillary tubes; and wherein said plurality of capillary tubes are arrayed in a two-dimensional array formed of plural rows of capillary tubes, each row of capillary tubes terminating at a different level from any other row of capillary tubes. - View Dependent Claims (55, 56, 57, 58, 59)
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49. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the second ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in the capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; a detector, including a source of collimated electromagnetic radiation having a wavelength that may excite the sample to emit radiation to detect organic sample emerging in the individual sample streams from the capillary tubes, said source being aligned to provide collimated light through the organic sample drawn from the capillary tubes by the sheath fluid, and; wherein said capillary tubes are arrayed in a two-dimensional array formed of plural rows of capillary tubes, each row of capillary tubes terminating at a different level from any other row of capillary tubes. - View Dependent Claims (63)
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50. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity, the second ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid into the interior cavity of said flow chamber to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in the capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; a detector, including a source of collimated electromagnetic radiation having a wavelength that may excite the sample to emit radiation to detect organic sample emerging in the individual sample streams from the capillary tubes, said source being aligned to provide collimated light through the organic sample drawn from the capillary tubes by the sheath fluid, and; wherein said means to supply sheath fluid includes; a reservoir of sheath fluid; a sheath fluid supply tube connected between the reservoir and the chamber; and means to prevent bubbles in the sheath fluid supply tube from entering into the chamber.
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60. An analyzer for analyzing an organic sample, the analyzer comprising:
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a plurality of capillary tubes arrayed side by side, each capillary tube having first and second ends, the second ends of the capillary tubes terminating adjacent each other and the first ends being connectable to a source of organic sample; a flow chamber having an interior cavity and a side wall encircling the interior cavity, the second ends of the capillary tubes terminating inside the interior cavity; means to supply sheath fluid between the side wall and the capillary tubes to provide a flow of sheath fluid past the second ends of the capillary tubes such that any organic sample in the capillary tubes is drawn by the flow of sheath fluid in individual sample streams from the second ends of the capillary tubes; means to force organic sample through the capillary tubes from the first ends of the capillary tubes to the second ends of the capillary tubes; a detector to detect organic sample emerging in the individual sample streams form the capillary tubes; and wherein the encircling side wall including wall portions which taper towards each other from a separation that is greater than the sum of the capillary tube diameters to a separation that is less than the sum of the capillary tube diameters.
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Specification