US3699336A
Expired / Lapsed
US
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Biological cell analyzing system
Assignee: Hycel Inc
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Filing: 1969-08-15
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Granted: 1972-10-17
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Expires: 1989-08-15
Abstract
Abstract A biological cell analyzing system which is capable of automatically categorizing unstained biological cells as normal or non-normal. The cells are made to flow through a transparent tube in single file and are scanned with a mixture of ultraviolet and visible light. The cytoplasm and nucleus of each cell absorb ultra-violet radiation to different degrees, and the emergent light signal, as modulated by the scanned cells, is detected, amplified, and extended to a data processor which logically analyzes the signal from each cell on a real-time basis. The visible light signal is subtracted from the ultraviolet light signal to improve the signal/noise ratio of the latter, and to automatically cancel out non-biological debris. A number of acceptance tests are electronically performed on each cell, and if any of the tests is failed the cell is categorized as non-normal. Ambiguous conditions, resulting for example from the clumping of cells, are identified and separately counted. The system can process up to several thousand cells from a single sample during a one-minute run.
Inventors
- 👤 Melvin P Ehrlich
- 👤 Milton Stoller
- 👤 Stanley Grand
- 👤 Robert De Cote
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 12:14
CPC Classifications
G; G01; G01N; G01N15/00; G01N15/10; G01N15/14; G01N15/1468; G01N15/147
Claims Analysis
Total Claims: 36
Claim 1
Independent Claim
74 words
A system for analyzing biological cells comprising a capillary tube, means for controlling a substantially laminar flow through said capillary tube of a carrier solution containing biological cells therein, means for irradiating said capillary tube with a source of movable focused light of wavelengths which are absorbed by said biological cells, and means for detecting the light transmitted through said capillary tube to determine characteristics of the biological cells flowing through said capillary tube.
Claim 2
Independent Claim
74 words
A system for analyzing biological cells comprising a capillary tube, means for controlling a substantially laminar flow through said capillary tube of a carrier solution containing biological cells therein, means for irradiating said capillary tube with a source of movable focused light of wavelengths which are absorbed by said biological cells, and means for detecting the light transmitted through said capillary tube to determine characteristics of the biological cells flowing through said capillary tube.
Claim 3
Dependent Claim
46 words
A system in accordance with claim 1 wherein the inner diameter of said capillary tube and the rate of flow of said carrier solution through said capillary tube are such that said biological cells are constrained to flow in essentially single file through said capillary tube.
Claim 4
Dependent Claim
26 words
A system in accordance with claim 2 wherein a substantial portion of the energy of said light is contained in ultra-violet wavelengths lower than 300 millimicrons.
Claim 5
Dependent Claim
44 words
A system in accordance with claim 1 wherein a substantial portion of the energy of said light is contained in ultra-violet wavelengths lower than 300 millimicrons and said light is irradiated on said capillary tube in the form of line sweeps across said tube.
Claim 6
Dependent Claim
69 words
A system in accordance with claim 4 wherein said detecting means includes means responsive to the instantaneous intensity of the ultra-violet light at wavelengths Below 300 millimicrons transmitted through said capillary tube for deriving a signal proportional thereto and means for distinguishing between nuclear and cytoplasmic cellular material within said capillary tube along any line sweep across said tube in accordance with the instantaneous magnitude of the derived signal.
Claim 7
Dependent Claim
46 words
A system in accordance with claim 5 wherein said capillary tube has an inner diameter and the rate of flow of said carrier solution through said capillary tube are such that said biological cells are controlled to flow in essentially single file through said capillary tube.
Claim 8
Dependent Claim
82 words
A system in accordance with claim 6 wherein a portion of the total energy in said light is contained in wavelengths above 300 millimicrons, and said detecting means includes means for detecting the instantaneous intensity of the light at wavelengths above 300 millimicrons transmitted through said capillary tube and for generating a signal proportional thereto, and means for subtracting the generated signal from said derived signal such that the signal/noise ratio of the signal operated upon by said distinguishing means is increased.
Claim 9
Dependent Claim
80 words
A system in accordance with claim 5 wherein a portion of the total energy in said light is contained in wavelengths above 300 millimicrons, and said detecting means includes means for detecting the instantaneous intensity of the light at wavelengths above 300 millimicrons transmitted through said capillary tube for generating a signal proportional thereto and means for comparing the instantaneous intensity of said generated signal to a threshold value to determine the presence of a histiocyte in said capillary tube.
Claim 10
Dependent Claim
65 words
A system in accordance with claim 8 further including means for controlling a flow through said capillary tube of biological cells from different samples in succession, and means responsive to the determination of a number of histiocytes having flowed through said capillary tube which exceeds a predetermined number during the flow of cells from a particular sample for indicating that the sample contains lung cells.
Claim 11
Dependent Claim
109 words
A system in accordance with claim 5 further including means for inserting said capillary tube into different containers in succession, each container containing sample cells from a different person, means for controlling the flow of cells from each sample through said capillary tube for a predetermined time interval prior to the change of samples, means for categorizing the cells flowing through said capillary tube in accordance with the operation of said detecting means, and means for delaying the categorizing of cells until cells from each sample have flowed through said capillary tube for a predetermined time interval and have cleaned the capillary tube of cells from the previous sample.
Claim 12
Dependent Claim
34 words
A system in accordance with claim 3 wherein said capillary tube is made of quartz and said irradiating means includes quartz objective and condenser lenses disposed on opposite sides of said quartz capillary tube.
Claim 13
Dependent Claim
39 words
A system in accordance with claim 11 further including a quartz plate for supporting said quartz capillary tube adjacent to said quartz objective lens and a droplet of oil bridging said quartz objective lens and said quartz capillary tube.
Claim 14
Independent Claim
117 words
A system for analyzing biological cells comprising a scanning station, means for controlling the movement of biological cells in essentially single file past said scanning station, means for scanning said cells at the scanning station with line scans of ultra-violet light having a substantial portion of its energy at wavelengths below 300 millimicrons, means for detecting the instantaneous intensity of the ultra-violet light transmitted through said cells at the scanning station for deriving a signal proportional thereto, means for distinguishing between nuclear and cytoplasmic cellular material along any line scan through a cell in accordance with the derived signal, and means responsive to said distinguishing Means for categorizing a cell in one of at least two groups.
Claim 15
Independent Claim
117 words
A system for analyzing biological cells comprising a scanning station, means for controlling the movement of biological cells in essentially single file past said scanning station, means for scanning said cells at the scanning station with line scans of ultra-violet light having a substantial portion of its energy at wavelengths below 300 millimicrons, means for detecting the instantaneous intensity of the ultra-violet light transmitted through said cells at the scanning station for deriving a signal proportional thereto, means for distinguishing between nuclear and cytoplasmic cellular material along any line scan through a cell in accordance with the derived signal, and means responsive to said distinguishing Means for categorizing a cell in one of at least two groups.
Claim 16
Dependent Claim
58 words
A system in accordance with claim 13 wherein said distinguishing means is operative to indicate the scanning of cytoplasmic cellular material responsive to the magnitude of said derived signal exceeding a first threshold level and is operative to indicate the scanning of nuclear cellular material responsive to the magnitude of said derived signal exceeding a second threshold level.
Claim 17
Dependent Claim
36 words
A system in accordance with claim 14 further including means for maintaining said derived signal below said first threshold level at time periods corresponding to the leading and trailing portions of each of said line scans.
Claim 18
Dependent Claim
51 words
A system in accordance with claim 14 further including means for characterizing each scanned cell as having one or more of a predetermined group of non-normal characteristics in accordance with the time intervals during each line scan through the cell when said derived signal exceeds said first and second threshold levels.
Claim 19
Dependent Claim
61 words
A system in accordance with claim 16 further including means for deriving an annotation signal representative of the non-normal characteristics of each scanned cell, and means for combining said annotation signal and said derived signal in a form suitable for imaging the cell represented by said derived signal on a television display together with a code representative of its non-normal characteristics.
Claim 20
Dependent Claim
69 words
A system in accordance with claim 14 further including means for deriving an annotation signal indicative of the groups in which each cell has been categorized, and means for combining said annotation signal and said derived signal in a form suitable for imaging the cell represented by said derived signal on a television display together with a code representative of the groups in which said cell has been categorized.
Claim 21
Dependent Claim
93 words
A system in accordance with claim 13 further including means for scanning said cells with line scans of light having a portion of its energy at wavelengths above 300 millimicrons, means for detecting the instantaneous intensity of the light at wavelengths above 300 millimicrons transmitted through said cells for generating a signal proportional thereto, means for comparing the instantaneous magnitude of said generated signal to a threshold level, and means responsive to the instantaneous magnitude of said generated signal exceeding said threshold level for registering that the cell being scanned is a histiocyte.
Claim 22
Dependent Claim
36 words
A system in accordance with claim 13 wherein said scanning station includes a quartz capillary tube through which said cells move, and quartz objective and condenser lenses disposed on opposite sides of said quartz capillary tube.
Claim 23
Dependent Claim
39 words
A system in accordance with claim 20 further including a quartz plate for supporting said quartz capillary tube adjacent to said quartz objective lens, and a droplet of oil bridging said quartz objective lens and said quartz capillary tube.
Claim 24
Dependent Claim
80 words
A system in accordance with claim 13 wherein a portion of the total energy in said light is contained in wavelengths above 300 millimicrons, and said detecting means includes means for detecting the instantaneous intensity of the light at wavelengths above 300 millimicrons transmitted through said cells for generating a signal proportional thereto, and means for subtracting the generated signal from said derived signal such that the signal/noise ratio of the signal operated upon by said distinguishing means is increased.
Claim 25
Dependent Claim
113 words
In a system for scanning biological cells at a scanning station the improvement comprising a capillary tube disposed at said scanning station, and means for controlling a flow through said capillary tube of a carrier solution containing therein the biological cells to be scanned, said capillary tube having an inner diameter and the rate of flow of said carrier solution being such that said biological cells flow in essentially single file through said capillary tube wherein said cells are scanned by a source of movable ultra-violet light and said capillary tube is made of quartz, said system further including quartz objective and condenser lenses disposed on opposite sides of said quartz capillary tube.
Claim 26
Dependent Claim
113 words
In a system for scanning biological cells at a scanning station the improvement comprising a capillary tube disposed at said scanning station, and means for controlling a flow through said capillary tube of a carrier solution containing therein the biological cells to be scanned, said capillary tube having an inner diameter and the rate of flow of said carrier solution being such that said biological cells flow in essentially single file through said capillary tube wherein said cells are scanned by a source of movable ultra-violet light and said capillary tube is made of quartz, said system further including quartz objective and condenser lenses disposed on opposite sides of said quartz capillary tube.
Claim 27
Dependent Claim
38 words
A system in accordance with claim 23 further including a quartz plate for supporting said quartz capillary tube adjacent said quartz objective lens, and a droplet of oil bridging said quartz objective lens and said quartz capillary tube.
Claim 28
Independent Claim
104 words
A system for line scanning biological cells comprising means for irradiating said biological cells with ultra-violet light of wavelengths below 300 millimicrons in the form of line scans, means for deriving a signal dependent upon the ultra-violet light absorption characteristics of a scanned cell, means for simultaneously irradiating said biological cells with light of wavelengths above 300 millimicrons in the form of lines scans, means for generating a signal dependent upon the above 300 millimicron light absorption characteristics of a scanned cell, and means for processing the derived signal in accordance with the generated signal to increase the signal/noise ratio of said derived signal.
Claim 29
Independent Claim
104 words
A system for line scanning biological cells comprising means for irradiating said biological cells with ultra-violet light of wavelengths below 300 millimicrons in the form of line scans, means for deriving a signal dependent upon the ultra-violet light absorption characteristics of a scanned cell, means for simultaneously irradiating said biological cells with light of wavelengths above 300 millimicrons in the form of lines scans, means for generating a signal dependent upon the above 300 millimicron light absorption characteristics of a scanned cell, and means for processing the derived signal in accordance with the generated signal to increase the signal/noise ratio of said derived signal.
Claim 30
Dependent Claim
79 words
A system in accordance with claim 25 wherein the nucleus and cytoplasm of the biological cells which are scanned absorb above 300-millimicron and below 300-millimicron light to different degrees, and further including means for distinguishing between nuclear and cytoplasmic regions of a cell in accordance with said derived signal exceeding first and second threshold levels, said processing means including means for subtracting said generated signal from said derived signal to facilitate the distinguishability of nuclear and cytoplasmic cell regions.
Claim 31
Independent Claim
57 words
A system for detecting histiocytes comprising means for controlling the line scanning of biological cells with light of wavelengths above 300 millimicrons, means for generating a signal dependent upon the light absorption characteristics of a scanned cell, and means responsive to the generated signal exceeding a predetermined threshold level for characterizing a scanned cell as a histiocyte.
Claim 32
Independent Claim
57 words
A system for detecting histiocytes comprising means for controlling the line scanning of biological cells with light of wavelengths above 300 millimicrons, means for generating a signal dependent upon the light absorption characteristics of a scanned cell, and means responsive to the generated signal exceeding a predetermined threshold level for characterizing a scanned cell as a histiocyte.
Claim 33
Dependent Claim
103 words
A system in accordance with claim 27 wherein said line scanning controlling means includes a capillary tube and means for controlling a flow through said capillary tube of a carrier solution containing biological cells therein, said capillary tube having an inner diameter and the rate of flow of said carrier solution through said capillary tube being such that biological cells are controlled to flow in essentially single file, the flow rate of said biological cells through said capillary tube and the speed of said line scanning being such that said cells are scanned along lines approximately perpendicular to the direction of cell movement.
Claim 34
Independent Claim
92 words
A system for controlling line scans with focused ultra-violet light of flowing biological cells comprising a capillary tube, means for controlling a flow through said capillary tube of a carrier solution containing biological cells therein, means for generating successive ultra-violet light scans, an objective lens disposed on one side of said capillary tube for coupling said ultra-violet light to said capillary tube, a condenser lens disposed on the opposite side of said capillary tube, and means for generating an electrical signal in accordance with the ultra-violet light transmitted through said condenser lens.
Claim 35
Independent Claim
92 words
A system for controlling line scans with focused ultra-violet light of flowing biological cells comprising a capillary tube, means for controlling a flow through said capillary tube of a carrier solution containing biological cells therein, means for generating successive ultra-violet light scans, an objective lens disposed on one side of said capillary tube for coupling said ultra-violet light to said capillary tube, a condenser lens disposed on the opposite side of said capillary tube, and means for generating an electrical signal in accordance with the ultra-violet light transmitted through said condenser lens.
Claim 36
Dependent Claim
34 words
A system in accordance with claim 29 further including a plate for supporting said capillary tube adjacent to said objective lens and a droplet of oil bridging said objective lens and said capillary tube.
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) | 1975-10-17 | 1976-04-17 | 1976-10-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1979-10-17 | 1980-04-17 | 1980-10-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1983-10-17 | 1984-04-17 | 1984-10-17 | $7700.00 | Window Closed / Lapsed |