US 12,618,765 B2Granted

Cytometer and a method of cytometry

AssigneeCity University of Hong Kong

InventorsHiu-wai Raymond Lam, Wei Huang

Life of this patent

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Abstract

A cytometer includes a plurality of measurement sections, each comprising first and second sidewalls and a base therebetween, the sidewalls and base defining a channel portion extending from an entrance to an exit; an electrode group arranged on the opposite sides of the base and part way between the entrance and exit, the electrode group comprising an upstream electrode, a centre electrode and a downstream electrode in the way of a trajectory between the entrance and exit, and in respective order; the measurement sections being connected together to form at least one measurement channel comprising a plurality of the channel portions connected together in series; and, a lock-in amplifier; the central electrode of each group connected to the excitation signal port of the lock-in amplifier, and the upstream and downstream electrodes connected to the voltage differential input ports of the lock-in amplifier.

Claims14

Dependent claims

A cytometer comprising

a plurality of measurement sections, each measurement section comprising
first and second sidewalls and a base extending therebetween, the first and second sidewalls and base defining a channel portion therebetween, the sidewalls and base extending from an entrance to an exit;
an electrode group arranged on the opposite side of the base to the channel portion and part way between the entrance and exit, the electrode group comprising an upstream electrode, a downstream electrode and a center electrode, the electrodes being arranged such that as one travels from the entrance to the exit one passes over the upstream electrode, then the center electrode and then the downstream electrode;
the channel portion having a width measured in a direction normal to the sidewalls;
the measurement sections being connected together to form at least one measurement channel comprising a plurality of the channel portions connected together in series, with each channel portion of the measurement channel having a different width;
and,
at least one lock-in amplifier;
the electrode groups being configured such that for each group the central electrode is connected to the excitation signal port of a lock-in amplifier and the upstream and downstream electrodes are connected to the voltage differential input ports of the lock-in amplifier.

5 more elements

A method of cytometry comprising the steps of

(a) providing a cytometer, the cytometer comprising a
plurality of measurement sections, each measurement section comprising first and second sidewalls and a base extending therebetween, the first and second sidewalls and base defining a channel portion therebetween, the sidewalls and base extending from an entrance to an exit;
an electrode group arranged on the opposite side of the base to the channel portion and part way between the entrance and exit, the electrode group comprising an upstream electrode, a downstream electrode and a center electrode, the electrodes being arranged such that as one travels from the entrance to the exit one passes over the upstream electrode, then the center electrode and then the downstream electrode;
the channel portion having a width measured in a direction normal to the sidewalls;
the measurement sections being connected together to form at least one measurement channel comprising a plurality of the channel portions connected together in series, with each channel portion of the measurement channel having a different width;
and,
at least one lock-in amplifier;
the electrode groups being configured such that for each group the central electrode is connected to the excitation signal port of a lock-in amplifier and the upstream and downstream electrodes are connected to the voltage differential input ports of the lock-in amplifier;
(b) identifying the set of ripples in the output which are produced by passage of a cell along different channel portions of a single measurement channel;
(c) for at least two ripples α, β of the set of ripples which correspond to passage of the cell along channel portions ca and cp determining the peak-to-peak amplitudes Vppα and Vppβ of the ripples;
and,
(d) solving the simultaneous equations
Vppα=k(Ddeform2(Dcell,Wcα)+b)
Vppβ=k(Ddeform2(Dcell,Wcβ)+b)
to determine a cell surface charge k and the undeformed diameter of the cell where b is a constant, Wcα and Wcβ are the widths of the channel portions cα and cβ and Ddeform(Dcell,W) is the diameter of a deformed cell of undeformed diameter in a channel of width and is related to Dcell and W by the relation
4
3
⁢
π
⁡
(
D
cell
2
)
3
=
2
⁢
π
⁡
(
D
deform
2
)
2
⁢
(
W
2
)
-
2
⁢
π
3
⁢
(
W
2
)
3

50 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/161,005Filed 27 Jan 2023 · us provisional application
Priority: 28 Jan 2022
Published: US 2023/0243732 A13 Aug 2023
Granted: 5 May 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

G01N 15/1031
Investigating individual particles: by measuring electrical or magnetic effects
G01N 15/1429
Optical investigation techniques, e.g. flow cytometry: signal processing
G01N 15/0266
Investigating particle size or size distribution: with electrical classification
G01N 2015/1006
Investigating individual particles: for cytology