Impedance flow cytometry apparatus

Patent metadata

Field	Value
Publication number	US-12025547-B2
Application number	US-201917276697-A
Country	US
Kind code	B2
Filing date	Sep 16, 2019
Priority date	Sep 17, 2018
Publication date	Jul 2, 2024
Grant date	Jul 2, 2024

Abstract

Impedance flow cytometry apparatus comprises: a flow channel for carrying a flow of fluid comprising particles suspended in an electrolyte from an inlet to an outlet; a first electrode group and a second electrode group, each electrode group providing first and second current paths through fluid flowing in the flow channel; wherein each electrode group comprises: a first signal electrode to provide to the first current path a first electrical signal of frequency, magnitude and phase; a second signal electrode to provide to the second current path a second electrical signal of substantially equal frequency and magnitude as the first electrical signal and of opposite phase to the first electrical signal; and one or more measurement electrodes to detect current flow in the first current path and the second current path and produce a summed signal representing the sum of the current flow in the first current path and the current flow in the second current path; wherein the first electrode group produces a first summed signal and the second electrode group produces a second summed signal; and circuitry to determine a differential signal representing the difference between the first summed signal and the second summed signal.

First claim

The invention claimed is:

1. Impedance flow cytometry apparatus comprising:
a flow channel for carrying a flow of fluid comprising particles suspended in an electrolyte from an inlet to an outlet;
a first electrode group and a second electrode group, each electrode group providing first and second current paths through fluid flowing in the flow channel;
wherein each electrode group comprises:
a first signal electrode to provide to the first current path a first electric signal of frequency, magnitude and phase;
a second signal electrode to provide to the second current path a second electrical signal of substantially equal frequency and magnitude as the first electrical signal and of opposite phase to the first electrical signal; and
one or more measurement electrodes to detect current flow in the first current path and the second current path and produce a summed signal representing the sum of the current flow in the first current path and the current flow in the second current path;
wherein the first electrode group produces a first summed signal and the second electrode group produces a second summed signal; and

circuitry to determine a differential signal representing the difference between the first summed signal and the second summed signal.

2. Impedance flow cytometry apparatus according to claim 1 , further comprising a processor configured to receive the differential signal, and calculate and output an impedance signal representing impedance properties of particles in fluid flowing in the flow channel.

3. Impedance flow cytometry apparatus according to claim 2 , in which the processor is configured to identify, within the impedance signal, impedance values arising from the particles in the fluid.

4. Impedance flow cytometry apparatus according to claim 1 , further comprising a processor configured to receive the differential signal, and identify within the differential signal occurrences of differential values arising from the presence of particles in the fluid flowing in the channel.

5. Impedance flow cytometry apparatus according to claim 2 , in which the processor is configured to calculate and output an impedance signal corresponding to each of one or more frequencies comprised in the first and second electrical signals.

6. Impedance flow cytometry apparatus according to claim 5 , in which the one or more frequencies comprises a low frequency and a high frequency larger than the low frequency.

7. Impedance flow cytometry apparatus according to claim 2 , in which the processor is further configured to correlate the impedance signal with measurements of optical properties of the particles.

8. Impedance flow cytometry apparatus according to claim 1 , in which, within an electrode group, the one or more measurement electrodes comprise a first measurement electrode to detect current flow in the first current path and a second measurement electrode to detect current flow in the second current path.

9. Impedance flow cytometry apparatus according to claim 1 , in which, within an electrode group, the one or more measurement electrodes comprises a single electrode to detect current flow in both the first current path and the second current path.

10. Impedance flow cytometry apparatus according to claim 1 , in which, within an electrode group, the one or more measurement electrodes are configured to produce a summed current, being the sum of the current flow in the first current path and the current flow in the second current path, and the electrode group has an associated current-to-voltage converter to convert the summed current to a voltage which is output as the summed signal from the electrode group.

11. Impedance flow cytometry apparatus according to claim 1 , in which an electrode group has associated current-to-voltage converters to convert the detected current flow in the first current path and the detected current flow in the second current path into voltages, which are summed to obtain the summed signal from the electrode group.

12. Impedance flow cytometry apparatus according to claim 1 , in which the first signal electrode of the first electrode group and the first signal electrode of the second electrode group, or the second signal electrode of the first electrode group and the second signal electrode of the second electrode group, comprise a single signal electrode shared by the first electrode group and the second electrode group.

13. Impedance flow cytometry apparatus according to claim 1 , in which the signal electrodes are located substantially opposite to the measurement electrodes to provide current paths substantially transverse to a direction of flow in the flow channel from the inlet to the outlet.

14. Impedance flow cytometry apparatus according to claim 13 , in which the signal electrodes and the measurement electrodes are arranged as electrode pairs each defining a current path, the electrode pairs having a substantially uniform spacing along the flow channel.

15. Impedance flow cytometry apparatus according to claim 1 , in which signal electrodes and measurement electrodes of each current path are located on a same side of the flow channel to provide current paths substantially along a direction of flow in the flow channel from the inlet to the outlet.

16. Impedance flow cytometry apparatus according to claim 1 , in which at least one current path is substantially transverse to a direction of flow in the flow channel from the inlet to the outlet, and at least one current path is substantially parallel to the direction of flow.

17. Impedance flow cytometry apparatus according to claim 16 , in which in each of the first electrode group and the second electrode group, one of the first current path and the second current path is substantially transverse to the direction of flow and the other of the first current path and the second current path is substantially parallel to the direction of flow.

18. Impedance flow cytometry apparatus according to claim 1 , in which, within an electrode group, the electrodes are arranged such that the first current path and the second current path are at different positions along a direction of flow in the flow channel from the inlet to the outlet.

19. Impedance flow cytometry apparatus according to claim 1 , in which each electrode group comprises additional signal electrodes and measurement electrodes to provide one or more further pairs of first and second current paths.

20. Impedance flow cytometry apparatus according to claim 1 , in which a cross-sectional size of the flow channel in a plane orthogonal to a direction of flow in the flow channel from the inlet to the outlet varies along the direction of flow.

21. Impedance flow cytometry apparatus according to claim 20 , in which the flow channel comprises a first region associated with the first electrode group and having a first cross-sectional size, and a second region associated with the second electrode group and having a second cross-sectional size different from the first cross-sectional size.

22. Impedance flow cytometry apparatus according to claim 1 , and further comprising one or more signal conditioning electrodes positioned and held at potential so as to minimise current flow between signal electrodes and measurement electrodes which are not associated with a same current path.

23. Impedance flow cytometry apparatus according to claim 1 , further comprising one or more electrical signal sources to supply the signal electrodes with the fi

Assignees

• Univ Southampton

Inventors

• Morgan Hywel
• Spencer Daniel

Classifications

• G01N2015/1006

  for cytology · CPC title

• G01N15/1436

  the optical arrangement forming an integrated apparatus with the sample container, e.g. a flow cell · CPC title

• B01L2300/0645

  Electrodes · CPC title

• B01L3/502761

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title

• B01L3/502715

  characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces · CPC title