Measuring and testing – Liquid analysis or analysis of the suspension of solids in a... – Viscosity
Patent
1992-08-21
1994-07-12
Williams, Hezron E.
Measuring and testing
Liquid analysis or analysis of the suspension of solids in a...
Viscosity
73 5409, G01N 1104
Patent
active
053277775
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the measurement of biological cell rheological properties and to apparatus for use in such measurement.
The rheology of biological cells is of considerable interest to workers in the medical and pharmaceutical fields. Of particular interest is the sub-discipline of microrheology. This concerns inter alia the flow of cells in channels having dimensions approaching those of the cells themselves. One example of this is the flow of human red and white blood cells in the capillary networks of the human body. In these vessels cells transit serially while undergoing deformation due to the capillary diameter being less than the cell diameter. The degree of the cells' deformability is related to the elastic constants of the cells which are, in turn, related to biochemical properties of the cells. It is suggested that some disease states can affect the biochemistry and hence deformability of the cell, and in doing so symptoms of circulatory disease result. For example, the disease "Diabetes Mellitus" can result in progressive circulatory dysfunction; this is believed to be contributed to by a change in erythrocyte cellular deformability.
Due to the extreme difficulty of in-vivo measurement of these properties recourse is made to in-vitro techniques. Unfortunately the rheological properties of cell suspensions make it impossible to determine accurately microrheological characteristics from macrorheological measurements. In an attempt to overcome this, several techniques have been developed to measure cells passing through fabricated microchannels. Potentially the most accurate of these existing techniques is to pass cells individually through glass micropipettes while measuring their flow properties.
Micropipettes have offered the most physiologically analogous technique, but several problems have restricted their application. These fall into two groups. Firstly, fabrication and utilization related factors limit measurement accuracy. Secondly, due to several factors the number of cells of one sample that can be measured is statistically too small for detailed analysis. The latter limitation precludes the use of this technique, in its current implementation, for the identification of small sub-populations of cells with aberrant rheological properties.
Macroscopic filtration techniques have been recognized as an alternative, and have been developed in parallel, but there have been problems of reproducibility of results, due to the differences in diameter between different pores of the same membrane and between different membranes. Some refined forms of filtrometer, the Single Erythrocyte Rigidometer (SER) and its lineal development, the Cell Transit Analyser (CTA) overcome the intra analysis reproducibility problem by means of a continuous flow technique through one or more pores in a membrane. Furthermore, operator effects are virtually removed by automating the erythrocyte transit measurement. We categorize the CTA as a Multi Channel Non Concurrent Transit device (MCNCT). The CTA and SER do, however, suffer from the drawback that it is impossible in current devices to differentiate between the steady state flow of an erythrocyte within a pore in the membrane and entrance effects as the erythrocyte initially deforms to enter the pore: only a global `occlusion time` is measured, i.e. the time taken for a cell to pass through the pore and re-appear on the other side. This drawback is related to the difficulty of fabricating a device of this form that offers a means of monitoring the cells' "velocity profile" during the "transit" as distinct from measuring the global "occlusion time".
A further disadvantage of MCNCT devices is that they do not offer a higher cell throughput than an SER. This is due to the potential ambiguities that would result from concurrent transits being monitored as a composite signal. As a result only one pore of the MCNCT can contain a cell at given time. This is achieved by using a low haematrocrit of about 10 and attempting to reject occasional multiple transits by an a
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Kaye Paul H.
Tracey Mark
Francies Valerie
University of Hertfordshire
Williams Hezron E.
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