Biological cell analysis

Claim 3

A method as defined in claim 1 wherein a series of at least three different discrete current values are produced within tHe test liquid, at least one value of which is below, and at least two other values of which are above, that at which a change in resistivity occurs.

Claim 4

A method as defined in claim 1 wherein said step of producing an electrical current within the test liquid is carried out by applying an electric potential between two electrodes.

Claim 5

A method as defined in claim 1 wherein said steps of producing an electrical current and of monitoring the resistance of the electrical current path are carried out as part of a Coulter measuring process during which said step of varying is carried out, a pulse analysis being effected for the resulting pulses for determining the resistivity of the test liquid, and in which the amplitude of each pulse is proportional to the current value corresponding to that pulse, and said step of monitoring includes determining the discrete current value at which the value of the proportional relationship between pulse amplitude and current value changes.

Claim 6

A method as defined in claim 4 for determining the physiological properties of the native cells, wherein said step of monitoring includes observing the change in he value of the proportional relationship between pulse amplitude and current value for measuring the conductivity of the cell plasma.

Claim 7

A method as defined in claim 4, further comprising the step of amplifying the pulses and varying the amplification of the pulses in at least an approximately inverse proportionality with changes in the current values.

Claim 8

An arrangement for observing native biological cells in a test liquid containing suspended biological cells, comprising, in combination: particle counting means for counting and classifying the cells suspended in the test liquid in accordance with the Coulter process, said counting means including two vessels for holding the test liquid, and having their interiors in communication with one another through a small measuring opening; means for producing a pressure difference between said vessels for causing the test liquid to flow through said measuring opening together with suspended biological cells from one vessel to the other; two electrodes, each immersed in the test liquid in a respective one of said vessels; electric potential applying means connected between said electrodes for producing a potential difference between said electrodes; electrical measuring means connected between said electrodes for measuring the current flowing between them; and means connected to said potential applying means for varying the magnitude of the electrical current in the test liquid, while the test liquid and suspended cells are passing through said opening, between a series of discrete values over a range encompassing a current value at which a change in the resistivity of native biological cells occurs, whereby the measurement produced by said measuring means provides an indication of the occurrence of such change in resistivity.

Claim 9

An arrangement for observing native biological cells in a test liquid containing suspended biological cells, comprising, in combination: particle counting means for counting and classifying the cells suspended in the test liquid in accordance with the Coulter process, said counting means including two vessels for holding the test liquid, and having their interiors in communication with one another through a small measuring opening; means for producing a pressure difference between said vessels for causing the test liquid to flow through said measuring opening together with suspended biological cells from one vessel to the other; two electrodes, each immersed in the test liquid in a respective one of said vessels; electric potential applying means connected between said electrodes for producing a potential difference between said electrodes; electrical measuring means connected between said electrodes for measuring the current flowing between them; and means connected to said potential applying means for varying the magnitude of the electrical current in the test liquid, while the test liquid and suspended cells are passing through said opening, between a series of discrete values over a range encompassing a current value at which a change in the resistivity of native biological cells occurs, whereby the measurement produced by said measuring means provides an indication of the occurrence of such change in resistivity.

Claim 10

An arrangement as defined in claim 7 wherein the test liquid is an electrolyte solution.

Claim 11

An arrangement as defined in claim 8 wherein the electrolyte liquid in that one of said vessels which is at the highere pressure is substantially free of cell particles, and further comprising feeding means containing the cells to be counted and classified and having an exit opening disposed in that one of said vessels at the higher pressure, upstream of said measuring opening, for feeding cells into the flow of test liquid through said measuring opening.

Claim 12

An arrangement as defined in claim 9 wherein said electrical measuring means includes evaluating means for determining the amplitude of the pulses in dependence upon the various cell populations suspended in the test solution and providing an output signal indicative of the association of the pulse amplitudes with the electric current within the test liquid.

Claim 13

An arangement as defined in claim 10 wherein said means for varying the electrical current includes a transistor having its collector connected to one of said electrodes; and voltage means connected to the base electrode of said transistor for applying a variable voltage thereto.

Claim 14

An arrangement as defined in claim 11 wherein said voltage means include a voltage source and a voltage divider.

Claim 15

An arrangement as defined in claim 10 wherein said means for varying the electrical current includes: a transistor having its collector connected to one of said electrodes; and a variable resistance connected to the emitter of said transistor.

Claim 16

An arrangement as defined in claim 13 wherein said variable emitter resistance is a potentiometer connected to the emitter of said transistor.

Claim 17

An arrangement as defined in claim 14, further comprising a stepping motor for adjusting the setting of said potentiometer.

Claim 18

An arrangement as defined in claim 13 wherein said variable resistance comprises a plurality of resistors having respectively different resistance values and means for selectively connecting said resistors in the emitter circuit of said transistor.

Claim 19

An arrangement as defined in claim 10 wherein said means for varying the electrical current includes: a transistor having its collector connected to one of said electrodes; and voltage means connected for supplying a variable voltage to he emitter resistance of said transistor.

Claim 20

An arrangement as defined in claim 17 wherein said voltage means includes a voltage source and a variable voltage divider connected between said emitter and said voltage source.

Claim 21

An arrangement as defined in claim 10 wherein said means for varying the electrical current comprises: a differential amplifier having one input coupled to one of said electrodes; means for producing an adjustable reference voltage connected to a second input of said differential amplifier; and means connected to the output of said differential amplifier for providing a voltage to said one electrode which is regulated in response to the output of said differential amplifier.

Claim 22

An arrangement as defined in claim 19 wherein said means for producing a reference voltage includes a voltage source and a variable voltage divider connected between said source and said second input of said differential amplifier.

Claim 23

An arrangement as defined in claim 19 wherein said means for producing a reference voltage includes a voltage source, a potentiometer connected as a voltage divider across said voltage source and a stepping motor connected for driving the movable tap of said potentiometer.

Claim 24

An arrangement as defined in claim 10 wherein said electrical measuring means include amplifying means for amplifying the pulses in inverse proportion to variations in the electrical current in the test liquid, said amplifying means comprising: a preamplifier connected to one of said electrodes for receiving the pulses indicative of the cells passing through said measuring opening; a variable resistance voltage divider coupled to the output of the preamplifier; and means for varying the value of the resistance of said voltage divider in inverse proportion to variations in the electrical current in the test liquid.

Claim 25

An arrangement as defined in claim 22 wherein said electrical measuring means further include analyzing means coupled to the output of said preamplifier for analyzing the amplitude of the pulses.

Claim 26

An arrangement as defined in claim 10 wherein said electrical measuring means include amplifying means for amplifying the pulses in inverse proportion to variations in the electrical current in the test liquid, said amplifying means comprising: a preamplifier connected to one of said electrodes via a coupling capacitor for receiving the pulses indicative of the cells passing through the measuring opening; a variable resistance connected in the feedback path of said preamplifier; and means for varying the value of said variable resistance in inverse proportion to variations in the electrical current in the test liquid.

Claim 27

An arrangement as defined in claim 24 wherein said elEctrical measuring means further include analyzing means coupled to the output of said preamplifier for analyzing the amplitude of the pulses.