Flow cell device for monitoring blood or other cell suspension under flow

• US 5,656,501 A
• Filed: 06/06/1995
• Issued: 08/12/1997
• Est. Priority Date: 08/11/1993
• Status: Expired due to Fees

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: Chen, Shuqi, Yedgar, Saul, Gavish, Benjamin
• Primary Examiner(s): Le, Long V.
• Application Number:
  US08/466,026
• Time in Patent Office: 798 Days
• Field of Search: 436/63, 436/69, 436/174, 436/70, 436/180, 436/183, 436/807, 422/55, 422/58, 422/73, 422/99, 422/100, 422/104, 435/291, 356/39, 356/244, 356/246
• US Class Current: 436/63
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: Y10T 436/25 including sample preparation
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A flow cell for monitoring blood or any other cell suspension under flow prises a rigid transparent base having a pair of holes with inlets and outlets. One hole transfers the cell suspension from a supply to a flow channel and the other hole transfers the tested suspension back from the flow channel to a receiver. A flow plate is sandwiched between the base and a transparent plate. The flow channel is a wide hole in the middle of the flow channel plate which can be an integral part of either the base or the transparent plate. The transparent plate covers the flow channel plate and a rigid cover covers the transparent plate with a hole enabling a microscope objective to approach the flow channel plate. The transparent plate and the cover are attached to each other firmly by any conventional method or the transparent plate can be an integral part of the cover.

Claims

1. A flow cell device for monitoring blood or a cell suspension under flow, comprising:

a rigid transparent base having a pair of holes;

a transparent plate and a flow channel plate of a constant thickness sandwiched between the base and the transparent plate to define a flow channel of a constant depth in the form of a hole in a center portion of the flow channel plate, said flow channel depth allowing the flow of only a single layer of blood or cell suspension aggregates;

wherein each of said pair of holes is formed with an inlet and outlet, one said hole for transferring the cell suspension from a supply to the flow channel and the other hole for transferring said blood or suspension back from the flow channel to a receiver; and

a rigid cover covering the transparent plate and being formed with a hole enabling a microscope objective to approach the flow channel plate.

2. A flow cell device according to claim 1, wherein the flow cell is disposable.

3. A flow cell device according to claim 1, wherein the flow channel has a depth to enable detection of aggregation and disaggregation, cell deformability and shape, and cell-wall, cell-to-cell, and cell-to-extracellular-matrix interaction of blood and cell suspension.

4. A flow cell device according to claim 1, wherein a thickness of the flow channel plate is 20-40 microns to establish said flow channel depth.

5. A flow cell device according to claim 1 wherein the flow channel plate has a constant depth.

6. A flow cell device according to claim 1 wherein the flow channel plate has a constant cross section.

7. A flow cell device according to claim 3 wherein the flow channel plate has a variable width.

8. A flow cell device according to claim 1 wherein the flow channel plate has a polygonal cross-section.

9. A flow cell device according to claim 1 wherein the flow channel plate has a variable cross-section.

10. A flow cell device according to claim 7 wherein the flow channel plate hole has a rectangular or trapezoidal cross-section.

11. A flow cell device according to claim 1 wherein the base, the flow channel plate, the transparent plate and the cover are attached to each other by at least one of glue and screws.

12. A flow cell device according to claim 1 wherein said supply and receiver are at least one of syringes and flexible caps.

13. The flow cell device of claim 1, wherein said flow channel plate is of integral construction with the base.

14. The flow cell device of claim 1, wherein said flow channel plate is of integral construction with the transparent plate.

15. The flow cell device of claim 1, wherein said transparent plate is of integral construction with the cover.

16. A method for monitoring the behavior of cell suspensions under flow using a flow cell including a flow cell device for monitoring blood or a cell suspension under flow, comprising a rigid transparent base having a pair of holes, a transparent plate and a flow channel plate of a constant thickness sandwiched between the base and the transparent plate to define a flow channel of a constant depth in the form of a hole in a center portion of the flow channel plate, said flow channel depth allowing the flow of only a single layer of blood or cell suspension aggregates, wherein each of said pair of holes is formed with an inlet and outlet, one said hole for transferring the cell suspension from a supply to the flow channel and the other hole for transferring said blood or suspension back from the flow channel to receiver, and a rigid cover covering the transparent plate and being formed with a hole enabling a microscope objective to approach the flow channel plate, comprising the steps of:

(a) fixing a syringe with a cell suspension to be tested to the inlet hole of the rigid transparent base;

(b) fixing an empty syringe to the outlet hole of the said base; and

(c) pushing the piston of the syringe with the cell suspension and simultaneously pulling the piston of the empty syringe to move the single layer of blood or cell suspension aggregates back and forth through the flow channel.

17. A method according to claim 16, comprising the further steps of repeatedly reversing the roles of the receiver and supply to enable prolonged detection of the cell suspension under flow.

18. A method according to claim 16 wherein said syringes are flexible caps.

19. A computerized image analyzer system for detection and visualization of suspension cells under flow, comprising:

a flow cell device including a rigid transparent base having a pair of holes, a transparent plate, a flow channel plate of a constant thickness sandwiched between the base and the transparent plate to define a flow channel of a constant depth in the form of a hole in a center portion of the flow channel plate, and a rigid cover covering the transparent plate and being formed with a hole, said flow channel depth allowing the flow of only a single layer of blood or cell suspension aggregates, each of said pair of holes being formed with an inlet and outlet, one said hole for transferring the cell suspension from a supply to the flow channel and the other hole for transferring said blood or suspension back from the flow channel to a receiver;

a microscope being movably mounted to approach the flow channel through the cover hole;

a video camera mechanically connected to said microscope;

a computer and an image monitor both connected to each other and to the video camera; and

a pump force or generator that operates said supply or receiver, and being connected to the computer and to the flow cell device to direct the suspension back and forth in the flow cell device.