Method and apparatus for controlled instrumentation of particles with a filter device

• US 6,225,125 B1
• Filed: 10/14/1999
• Issued: 05/01/2001
• Est. Priority Date: 03/02/1990
• Status: Expired due to Fees

• Current Assignee: Cytyc Corporation (Hologic Incorporated)
• Original Assignee: Cytyc Corporation (Hologic Incorporated)
• Inventors: Lapidus, Stanley N.
• Primary Examiner(s): SNAY, JEFFREY R
• Application Number:
  US09/417,785
• Time in Patent Office: 565 Days
• Field of Search: 422/111, 422/112, 422/73, 422/82, 422/101, 436/10, 436/63, 436/177, 436/178, 73/61.72, 73/61.73, 210/87, 210/90, 210/321.65
• US Class Current: 436/63
• CPC Class Codes: C12M 41/36 of biomass, e.g. colony counters or by turbidity measurements electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404
• CPC Class Codes: G01N 1/2813 Producing thin layers of samples on a substrate, e.g. smearing, spinning-on G01N1/30 takes precedence
• CPC Class Codes: G01N 1/4077 by other techniques involving separation of suspended solids
• CPC Class Codes: G01N 15/0272 with screening; with classification by filtering B01D takes precedence
• CPC Class Codes: G01N 2015/0662 Comparing before/after passage through filter
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

A method and apparatus for the controlled instrumentation processing of cells and other particles with a filter device measures a parameter of the flow through the filter device of fluid carrying the particles. A measure of the change of the fluid flow through the filter device yields desired information for quantifying the particles and for quantifying the obstruction of the filter device by the particles. The method and apparatus typically operate automatically.

Claims

1. A method for collecting for image analysis a selected quantity of particles having a known average size above a threshold size and that are in a fluid medium, comprising the steps of

A. providing a flow path for the fluid medium, with the particles carried therein, across a filter device having a substantially uniform distribution of apertures of substantially uniform size for blocking particles above said threshold size and passing smaller particles,

B. applying a selected fluid signal to the flow path for producing flow of the liquid medium through said filter device, said signal-applying step including applying a succession of signal pulses to the fluid, including across said filter device,

C. measuring a parameter responsive to fluid flow through said filter device due to said applied fluid signal and which changes according to blockage of said filter device by particles above said threshold size,

D. terminating said fluid signal in response to a selected change in said measured parameter, and

E. transferring the particles collected on said filter device, after said selected change in said measured parameter, to an optical element for image analysis.

2. A method according to claim 1 wherein the parameter in the measuring step is fluid pressure.

3. A method according to claim 1 wherein the parameter in the measuring step is flow velocity.

4. A method for determining a measure responsive to the number of particles in a liquid medium, said method comprising the steps of

A. providing a flow path for a liquid medium with particles carried therein across a filter device that blocks particles larger than a selected threshold size and passes smaller particles,

B. applying a selected fluid signal to the flow path for at least a selected time, for producing flow of the liquid medium through said filter device, said signal-applying step including applying a succession of signal pulses to the fluid,

C. measuring, in response to each of selected ones of said signal pulses, a parameter responsive to the change in flow through said filter device, and

D. determining a selected change in said measured parameter responsive to the change in obstruction of said filter device by particles larger than said threshold size, during said selected time.

5. A method according to claim 4 wherein the parameter in the measuring step is fluid pressure.

6. A method according to claim 4 wherein the parameter in the measuring step is flow velocity.

7. A method according to claim 4 wherein the measuring step measures, for each of selected ones of said applied signal pulses, the time for a parameter of flow of the liquid through said filter device to equilibrate by a selected amount.

10. An apparatus according to claim 6 further comprising

D. means for determining a selected quantitative change in said measured parameter responsive to the change in obstruction of said filter means by particles larger than said threshold size, during said selected time.

8. Apparatus for collecting for image analysis a selected quantity of particles having a known average size above a threshold size and that are in a fluid medium, said apparatus comprising

A. filter means having a substantially uniform distribution of apertures of substantially uniform size for blocking particles above said threshold size and for passing smaller particles and means for providing a flow path for the fluid medium, with the particles carried therein, across said filter means,

B. means for applying a known fluid signal to the flow path for at least a selected time, for producing flow of the liquid medium through said filter device, said signal-applying step including applying a succession of signal pulses to the fluid, including across said filter means,

C. means for measuring a parameter responsive to fluid flow through said filter means due to said applied fluid signal and which changes according to blockage of said filter means by particles above said threshold size,

D. means for terminating said fluid signal in response to a selected change in said measured parameter, and

E. means for transferring particles collected on said filter means, after said selected change in said measured parameter, to an optical element for image analysis.

9. An apparatus for determining a quantitative measure responsive to the number of particles in a liquid medium, said apparatus comprising

A. filter means for blocking particles larger than a selected threshold size and for passing smaller particles and means for providing a flow path for a liquid medium with the particles carried therein across said filter means,

B. means for applying a selected fluid signal to the flow path for a least a selected time, for producing flow of the liquid medium through said filter means, said signal-applying means including means for applying a succession of signal pulses to the fluid, and

C. means for measuring in response to each of selected ones of said signal pulses, a parameter responsive to the change in flow of the liquid medium through said filter means.

11. An apparatus according to claim 9 in which said means for measuring includes means for measuring, for each of selected ones of said applied signal pulses, the time for a parameter of flow of the liquid through said filter means to equilibrate by a selected amount.

12. A method for collecting a selected quantity of particles having a known average size above a threshold level and that are dispersed in a fluid medium, said method comprising the steps of

A. flowing the fluid medium, with the particles carried therein, across a filter device that has a substantially uniform distribution of apertures of substantially uniform size for blocking cells above a threshold size and for passing smaller by applying a signal including a succession of signal pulses,

B. measuring a parameter responsive to obstruction of said filter device by the particles above said threshold size, for thereby counting the number of particles above said threshold size collected on said filter,

C. terminating flow of the fluid medium across the filter device in response to a selected change in said measured parameter, and

D. transferring the particles collected on said filter to cytological examination apparatus.

13. An apparatus for determining a quantitative measure responsive to the number of particles in a liquid medium, said apparatus comprising

A. filter means for blocking particles above a threshold size and passing smaller particles and means for providing a flow path for the fluid medium, with the particles carried therein, across said filter means,

B. means for applying a known fluid signal to the flow path for producing flow of the liquid medium through said filter device, said signal-applying including a succession of signal pulses to the fluid, including across said filter means,

C. means for measuring a parameter responsive to fluid flow through said filter means due to said applied fluid signal,

D. means for terminating said fluid signal in response to a selected change in said measured flow-responsive parameter, and

E. means for transferring particles collected on said filter means, after said selected change in said measured flow-responsive parameter, to cytological examination apparatus.