Chemistry: molecular biology and microbiology – Apparatus – Differentiated tissue perfusion or preservation apparatus
Patent
1996-12-10
1998-06-02
Horlick, Kenneth R.
Chemistry: molecular biology and microbiology
Apparatus
Differentiated tissue perfusion or preservation apparatus
4352871, 4352883, 4352972, 422 8201, 422104, C12M 300
Patent
active
057598460
DESCRIPTION:
BRIEF SUMMARY
SUMMARY
The present invention relates to the domain of electrophysiology and biochemistry and to the measuring devices in these domains.
The present invention relates to a new device which enables tissular explants or organotypic cultures to be kept alive, allowing the electrophysiological and biochemical activity of the tissue studied to be continuously measured and analyzed.
The invention relates more particularly to the manufacture of an interface between the biological tissue and a suitable electronic module. The complete system allows the study of the electrical phenomena which are produced in excitable tissue cultures and in particular in central nervous tissues during the culture, the regeneration or the differentiation of cells.
Subject matter of the biological/electronic interface is a study device. It is constituted by two half-cards forming the upper part and the lower part respectively of the interface.
A permeable and transparent membrane is fixed on to the lower part of the device. One or several slice cultures rest on it which can be continuously or discontinuously perfused with a liquid nutrient.
PRIOR ART
Various extracellular recordings of the electrophysiological activity have been previously performed using micro electrode arrays. Most of the technologies used were microphotolithography on different types of material, like silicon (Kovacs et al., 1992; Curtis et al., 1992), glass (Thomas et al., 1972; Pine et al., 1980; Novak et al., 1988; Gross et al., 1982 & 1993). From these microelectrode arrays, simultaneous stimulations and recording of neuronal activity were performed on monolayer networks (Gross et al., 1993).
So far, the longest recording periods on nervous slices did not exceed 14 hours. In order to improve the survival conditions of the tissue, perforation of the stand was performed by some authors (Boppart et al., 1992).
Usually two methods were used. The first, is an exterior stimulation and recording by the micro electrode array; the second, is a stimulation by the network and recording by a conventional glass micro pipette. All those systems involved a recording chamber placed in a Faraday cage and most of them needed a classical electrophysiological set-up (antivibration table, head stage, amplifier, stimulation unit, isolation unit, oscilloscope, micro manipulator, . . . ). In most cases the biological material used were dissociated neurones or acute slices. Cells or tissue were laid down onto a planar electrode array and most of the time, glia cells were in between neurons and the recording site, impeding correct recordings (Janossy et al., 1990).
So far, no available system provides the possibility to simultaneously stimulate and get multirecordings of electrophysiological activity on organotypic slice cultures from mammals central nervous system (CNS), outside a Faraday cage during several days.
This prior art may be well illustrated by the following references: (1992) p. 893--902
Most of these references relate to micro-electrode array, using microphotolithography technology.
The two following references may also be cited:
Ch. Reese and l. Giaever IEEE Engineering in Medicine and Biology 13 (1994) no.3 p.402-408 who describes biosensors made of a small gold electrode immersed in a cell culture medium. This sensor is devised to detect changing impedance consecutive to the attachment of the cells and their growth on the gold electrode, but does not allow the recording of activity of excitable cells.
P. Acquint and al. (Clinical Chemistry 40-1994-p. 1895-1809) disclose a silicon chip micromachined analyser. This system uses silicon technology to produce a pH and CO.sub.2 detector in biological fluids, but is not appropriate for the cell culture. This device is made to be implanted and not to study the survival or the growth of slices of culture tissue.
None of these systems allows the study of electrophysiological activity of nervous tissue slices. They cannot deliver any electrical stimulation nor collect the electrophysiological responses, evoked or spontaneous,
REFERENCES:
patent: 4889691 (1989-12-01), Argentieri
patent: 5064618 (1991-11-01), Baker et al.
patent: 5126034 (1992-06-01), Carter et al.
Keese et al., I.E.E.E. Eng. Med. Biol. 13(3), 402-408 (1994).
Correges Philippe
Stoppini Luc
Chemodyne S.A.
Horlick Kenneth R.
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