Electricity: measuring and testing – Determining nonelectric properties by measuring electric...
Patent
1995-04-07
1997-11-25
O'Shea, Sandra L.
Electricity: measuring and testing
Determining nonelectric properties by measuring electric...
G01N 3348
Patent
active
056916337
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This application is a .sctn.371 of PCT/GB93/01544
This invention relates in general to a method of and apparatus for determining an electrical property of a sample and more particularly to a method of and apparatus for determining the impedance of particles such as biological cells (for example, white or red blood cells).
BACKGROUND OF RELATED ART
An increased awareness of the altered cell structure in vascular diseases and cancers has led to the development of techniques for the analysis of cell structure parameters. Changes in the characteristics of the cell membrane or nucleus are characteristic of several disorders. It has been found that the electrical properties of a cell can provide details of the composition and dimensions of the cell and more particularly of changes in the characteristics of the cell membrane and nucleus. Electrical activity in cells is due to the exchange of ions across cell membranes, which gives rise to potential differences and characteristic impedances. An advantage of determining the properties of cells from their electrical characteristics is that the characteristics of individual cells can be determined.
It is known from a paper by Schmukler, R. et al. ("A New Transient Technique for Measurement of Isolated Cell Impedance", Proc. 10th N.E. Bioenging. Conf., IEEE Press, 213-216) to determine the impedance characteristics of blood cells by embedding them in a polycarbonate filter, applying a current step stimulus to the system including the filter and cells embedded therein, and detecting the transient response to the step. The impedance characteristics (and hence various properties of the cells) are then determined from the transient response.
This known technique suffers from the drawbacks firstly that data processing of the transient response to a step stimulus can be complicated, secondly that it does not permit continuous tests to be carried out on a population of cells, and thirdly that it is time-consuming and expensive (in particular, the filter requires frequent replacement). Thus the technique is basically a laboratory technique, incapable of use in clinical tests.
International Patent Application WO 88/03267 describes a device which uses multiple AC sources to determine impedance of a sample at several frequencies. The orifice through which the samples flows, forms part of the oscillator tuning circuit. Therefore the oscillator output is dependant upon the orifice impedance. To allow multiple oscillators and a DC current source a novel method of coupling to the orifice must be used. The device described suffers from two main drawbacks. Firstly cells are measured at discrete frequencies therefore the frequency response of the cell is poor. Secondly the design is very complex. This complexity results from the requirement for a multichannel front-end and the coupling mechanism.
U.S. Pat. No. 3,887,868 describes a simple device which counts the number of particles and uses a logic circuit to determine the average cell volume. There is no provision for measuring the AC characteristics of the cells.
EP 022,568 describes what appears to be a modification to the counter previously described and produces a new flow chamber which can prevent bubbles entering the orifice. This device does not measure the AC characteristics of the cell.
U.S. Pat. No. 4,296,373, indicates that the changes to the basic counter are to facilitate different particulate sensing zones for different size particles.
EP 0,435,166 describes a particle counting and size device which attempts to solve the problem of the coincident passage of cells. This is achieved by using a laser as the sensing element. No High Frequency measurements are made.
U.S. Pat. No. 4,438,390 describes a simple extension of an existing counter to improve the Signal to Noise Ratio mechanically. Summing several pulses together is a well known averaging technique for improving low level signal in signal processing. As the cell can only be used once several sets of electrodes allow the same effect as repea
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Abel Eric William
Belch Jill Janette Freda
Liu Ying
Tweedie Richard John
British Technology Group Limited
O'Shea Sandra L.
Phillips Roger
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