US3710933A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Multisensor particle sorter
Assignee: United States Atomic Energy Commission
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Filing: 1971-12-23
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Granted: 1973-01-16
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Expires: 1991-12-23
Abstract
Abstract An apparatus for rapidly and automatically analyzing and sorting minute particles on the basis of certain preselected characteristics. Particles flow in suspension through a flow chamber having multiple sensing means to detect preselected physical or chemical characteristics of each particle and then are jetted between charging electrodes and deflection plates. Signals from the sensors for each particle are compared with preset standards, and those droplets containing particles having characteristics not meeting those standards are automatically charged by the charging electrodes. The deflection plates provide a constant electric field which deflects charged droplets away from uncharged droplets, thus sorting particles on the basis of their conformance or nonconformance to standards set for the preselected characteristics. This apparatus is particularly applicable to the rapid and automatic sorting of biological cells.
Inventors
- 👤 M Fulwyler
- 👤 J Steinkamp
- 👤 J Coulter
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 09:06
CPC Classifications
G; G01; G01N; G01N15/00; G01N15/10; G01N15/1031; G01N15/12; G01N15/14; G01N15/1456; G01N15/1459; B; B01; B01J; B01J2219/00; B01J2219/00274; B01J2219/00277; B01J2219/00497; B01J2219/005; G01N15/149; G01N2015/1019; G01N2015/1024; G01N2015/1028; G01N2015/103; G01N15/1404; G01N2015/1406; G01N2015/1477; G01N2015/1486
Claims Analysis
Total Claims: 19
Claim 1
Independent Claim
219 words
An apparatus for rapidly analyzing and sorting minute particles on the basis of preselected characteristics or combinations of preselected characteristics which comprises a. a flow chamber, b. a high-intensity light source, c. means for introducing particles in suspension in a fluid into said flow chamber, d. multiple sensing means for detecting preselected physical and chemical characteristics of said particles in said flow chamber and producing analog electrical quantities related to said characteristics, e. means for comparing said analog electrical quantities with preselected standards for said characteristics or combination of said characteristics and producing an electrical sort signal when said quantities or combinations of said quantities are outside said preselected standards, f. means for jetting said fluid from said flow chamber, g. means for periodically disturbing the jet or produce uniformly sized droplets sufficiently small that substantially each particle is isolated in a single droplet, h. electrical charging means adjacent to the jet path at the droplet separation zone, i. electrical delay means whereby said sorting signal activates said electrical charging means at a time when a particle having characteristics outside said preselected standards is in said droplet separation zone, said charging means remaining inactivated unless said sorting signal is received, and j. electrical deflecting means whereby charged droplets are deflected to a separate receptacle from that for uncharged droplets.
Claim 2
Independent Claim
219 words
An apparatus for rapidly analyzing and sorting minute particles on the basis of preselected characteristics or combinations of preselected characteristics which comprises a. a flow chamber, b. a high-intensity light source, c. means for introducing particles in suspension in a fluid into said flow chamber, d. multiple sensing means for detecting preselected physical and chemical characteristics of said particles in said flow chamber and producing analog electrical quantities related to said characteristics, e. means for comparing said analog electrical quantities with preselected standards for said characteristics or combination of said characteristics and producing an electrical sort signal when said quantities or combinations of said quantities are outside said preselected standards, f. means for jetting said fluid from said flow chamber, g. means for periodically disturbing the jet or produce uniformly sized droplets sufficiently small that substantially each particle is isolated in a single droplet, h. electrical charging means adjacent to the jet path at the droplet separation zone, i. electrical delay means whereby said sorting signal activates said electrical charging means at a time when a particle having characteristics outside said preselected standards is in said droplet separation zone, said charging means remaining inactivated unless said sorting signal is received, and j. electrical deflecting means whereby charged droplets are deflected to a separate receptacle from that for uncharged droplets.
Claim 3
Dependent Claim
20 words
The apparatus of claim 1 wherein said preselected chemical and physical characteristics comprise small angle light scatter, fluorescence and volume.
Claim 4
Dependent Claim
119 words
The apparatus of claim 1 wherein said flow chamber contains a. means whereby said particles are made to pass along a narrow stream of fluid, said stream passing through a first region having a Coulter volume sensing orifice wherein the change of impedance produced by the passage of each particle is measured and a second region, termed a viewing region, wherein said stream intersects a beam of light from said high-intensity light source, b. an access port whereby said beam of light enters said viewing region, and c. multiple viewing ports whereby optical properties of said particles may be viewed and measured, and said means for jetting said fluid is a nozzle at the base of said flow chamber.
Claim 5
Dependent Claim
13 words
The apparatus of claim 3 wherein said high-intensIty light source is a laser.
Claim 6
Dependent Claim
43 words
The apparatus of claim 3 having means for delaying the analog electrical signal produced by the passage of each particle through said volume sensing orifice and correlating it with the analog electrical signals produced for that same particle by the optical sensing means.
Claim 7
Dependent Claim
18 words
The apparatus of claim 5 wherein the optical sensing means consist of a photodiode and a photomultiplier tube.
Claim 8
Dependent Claim
149 words
The apparatus of claim 3 wherein said means for causing said particles to pass along a narrow stream of fluid consists of a. a sample inlet tube for introducing said particles in suspension in said fluid into said flow chamber, said sample inlet tube extending substantially into said flow chamber, and b. a first sheath liquid inlet tube concentrically surrounding said sample inlet tube and extending somewhat beyond it into said flow chamber, said first sheath liquid inlet tube having a nozzle at its lower end in which is located said volume sensing orifice, whereby said particles on leaving said sample inlet tube are surrounded by a coaxial laminar flow of sheath liquid, said sheath liquid having a velocity sufficiently high to narrow the flow of particles in suspension to a stream of desired diameter and surround said stream substantially coaxially as it passes through said volume sensing orifice.
Claim 9
Dependent Claim
25 words
The apparatus of claim 7 wherein said viewing region is surrounded by a reservoir of sheath liquid, said reservoir extending substantially above said viewing region.
Claim 10
Dependent Claim
17 words
The apparatus of claim 8 wherein said reservoir is fed by a second sheath liquid inlet tube.
Claim 11
Dependent Claim
44 words
The apparatus of claim 9 wherein said second sheath liquid inlet tube extends to near the base of said reservoir, and said reservoir has a flushing outlet tube as its top whereby gases produced in said reservoir may be periodically or continuously flushed therefrom.
Claim 12
Dependent Claim
34 words
The apparatus of claim 10 wherein said sample inlet tube serves as one electrode for said volume sensing orifice and said second sheath liquid inlet tube serves as the second electrode for said orifice.
Claim 13
Dependent Claim
36 words
The apparatus of claim 9 wherein means are provided for controlling the pressures of liquids entering said flow chamber through said sample inlet tube, said first sheath liquid inlet tube, and second sheath liquid inlet tube.
Claim 14
Dependent Claim
11 words
The apparatus of claim 12 wherein said pressures are controlled differentially.
Claim 15
Dependent Claim
29 words
The apparatus of claim 9 wherein said means for periodically disturbing said jet consists of a piezoelectric crystal coupled to said flow chamber and oscillated at a desired frequency.
Claim 16
Dependent Claim
43 words
The apparatus of claim 9 wherein said nozzle in the base of said flow chamber extends into said reservoir to near the plane of said viewing region, and means are provided for aligning said volume sensing orifice with the orifice in said nozzle.
Claim 17
Dependent Claim
44 words
The apparatus of claim 15 wherein said alignment means consists of a plurality of adjusting screws uniformly spaced around said first sheath liquid inlet outside said flow chamber whereby said first sheath inlet tube is rotated about an axis located partially within said reservoir.
Claim 18
Independent Claim
515 words
An apparatus for rapidly sorting biological cells failing to meet preset standards of normality from cells meeting such standards by imparting an electrical charge to fluid droplets containing the abnormal cells and passing the charged droplets through a static electrical field whereby the charged droplets are deflected into a separate receptacle from that of uncharged droplets containing normal cells, which comprises in combination a. means for introducing a suspension of cells in fluid into a flow chamber, b. a flow chamber containing (1) means for causing said cells to pass substantially singly and in spaced relationship along a narrow stream, said stream having a first region wherein cell volume is measured and a second region, termed a viewing region, wherein a beam of laser light intersects the flow of cells in suspension, (2) an access port whereBy said beam of laser light enters said viewing region, (3) a first viewing port whereby the laser light, after intersecting said flow of cells may be viewed and measured, (4) a second viewing port at a substantial angle to said first viewing port whereby light given off by the excitation of said laser light of fluorescent dyes or stains attached to a cell or constituents of a cell may be viewed and measured, and (5) a nozzle whereby said cells in suspension are jetted into air, c. means for generating a first electrical signal proportional to the volume of each cell as it passes through said first region of said channel in said flow chamber, d. laser means for illuminating each cell as it passes through said second region of said channel, e. means for measuring the scatter in the laser light as it emerges from said first viewing port and generating a second electrical signal proportional to the amount of scatter, f. means for collecting and measuring the fluorescent light emitted through said second viewing port and generating a third electrical signal proportional to the amount of fluorescent light, g. means for delaying said first electrical signal and correlating said signal for each cell with said second and third signals produced by that same cell, h. means for comparing said signals or combinations of said signals with predetermined value ranges for such signals for cells considered to be normal, and producing a sort electrical signal if any of said first, second, and third signals or combinations of said signals are outside said predetermined value ranges, i. means for periodically disturbing the jet of fluid emerging from said flow chamber to produce uniformly sized droplets sufficiently small that substantially each cell is isolated in a single droplet, j. electrical charging means adjacent to the jet path at the droplet separation zone, k. electrical delay means whereby said sort signal is used to activate the electrical charging means adjacent to the jet path at a time when the cell determined to be abnormal is in the droplet separation zone, said charging means remaining inactivated unless said sort signal is received, and l. electrical deflecting means whereby charged droplets are deflected to a separate receptacle from that for uncharged droplets.
Claim 19
Independent Claim
515 words
An apparatus for rapidly sorting biological cells failing to meet preset standards of normality from cells meeting such standards by imparting an electrical charge to fluid droplets containing the abnormal cells and passing the charged droplets through a static electrical field whereby the charged droplets are deflected into a separate receptacle from that of uncharged droplets containing normal cells, which comprises in combination a. means for introducing a suspension of cells in fluid into a flow chamber, b. a flow chamber containing (1) means for causing said cells to pass substantially singly and in spaced relationship along a narrow stream, said stream having a first region wherein cell volume is measured and a second region, termed a viewing region, wherein a beam of laser light intersects the flow of cells in suspension, (2) an access port whereBy said beam of laser light enters said viewing region, (3) a first viewing port whereby the laser light, after intersecting said flow of cells may be viewed and measured, (4) a second viewing port at a substantial angle to said first viewing port whereby light given off by the excitation of said laser light of fluorescent dyes or stains attached to a cell or constituents of a cell may be viewed and measured, and (5) a nozzle whereby said cells in suspension are jetted into air, c. means for generating a first electrical signal proportional to the volume of each cell as it passes through said first region of said channel in said flow chamber, d. laser means for illuminating each cell as it passes through said second region of said channel, e. means for measuring the scatter in the laser light as it emerges from said first viewing port and generating a second electrical signal proportional to the amount of scatter, f. means for collecting and measuring the fluorescent light emitted through said second viewing port and generating a third electrical signal proportional to the amount of fluorescent light, g. means for delaying said first electrical signal and correlating said signal for each cell with said second and third signals produced by that same cell, h. means for comparing said signals or combinations of said signals with predetermined value ranges for such signals for cells considered to be normal, and producing a sort electrical signal if any of said first, second, and third signals or combinations of said signals are outside said predetermined value ranges, i. means for periodically disturbing the jet of fluid emerging from said flow chamber to produce uniformly sized droplets sufficiently small that substantially each cell is isolated in a single droplet, j. electrical charging means adjacent to the jet path at the droplet separation zone, k. electrical delay means whereby said sort signal is used to activate the electrical charging means adjacent to the jet path at a time when the cell determined to be abnormal is in the droplet separation zone, said charging means remaining inactivated unless said sort signal is received, and l. electrical deflecting means whereby charged droplets are deflected to a separate receptacle from that for uncharged droplets.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1976-01-16 | 1976-07-17 | 1977-01-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1980-01-16 | 1980-07-17 | 1981-01-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1984-01-16 | 1984-07-17 | 1985-01-16 | $7700.00 | Window Closed / Lapsed |