Surgery – Diagnostic testing – Structure of body-contacting electrode or electrode inserted...
Patent
1998-03-24
2000-02-29
Dvorak, Linda C. M.
Surgery
Diagnostic testing
Structure of body-contacting electrode or electrode inserted...
600373, 607 54, 607116, 607148, A61N 104
Patent
active
060320621
DESCRIPTION:
BRIEF SUMMARY
The invention concerns a microelectrode arrangement for locally-resolved, in particular extracellular, leakage measurement of electrical cell potentials or for electrical stimulation of networks of biological cells.
Biological cells or networks of biological cells such as for example cell cultures, tissue slices "in vitro" or biological tissue "in vivo" in electrophysiology are usually contacted by glass microelectrodes with electrolyte filling, or by metal microelectrodes. The electrodes are inserted into a cell by means of a so-called micromanipulator (intracellular process), brought into close contact with a cell membrane (patch clamp process), or brought into the vicinity of the cell membrane (extracellular process) so that the microelectrodes are connected in an electrically-conductive way to the biological cells of the network by way of an electrolyte solution. The disadvantage of these contacting processes is that only one, or with great expense, only a few cells can be contacted simultaneously and as a result, no network characteristics can be examined.
For this reason attempts have been made in recent times to contact a network of biological cells at many places concurrently, by means of microstructured microelectrodes deposited onto a substrate (carrier) by methods known from microelectronics, to leak electrical cell potentials in an extracellular way or to be able to electrically stimulate the cells. In this, the microelectrodes should be arranged in the highest possible density in order to achieve high local resolution. Furthermore, the electrical potentials of the cells should be leaked as far as possible simultaneously, i.e. in a parallel way, or electrical potentials for stimulating the network should be able to be applied to these cells simultaneously, in order to achieve a high temporal resolution.
There is however the problem that electrical leads from the individual microelectrodes have to be conducted in an insulated way right up to an electronic device for measuring or stimulation, or similar. The multitude of parallel leads insulated from each other limits the local resolution of the microelectrode arrangement.
Another option is, for each microelectrode to accommodate an integrated electronic switch on the substrate and to connect (select) the microelectrodes to the measuring or stimulation electronics by multiplex operation individually or in groups, in time sequence. This necessitates very great expense in integrated circuit engineering (VLSI technology) and thus considerably increases the cost of the microelectrode arrangement. In addition, the local resolution remains limited, due to the electronic switches which need to be accommodated on the substrate. Furthermore, the microelectrodes can no longer be selected concurrently, but only individually or in groups in sequence; the temporal resolution of the leakage or stimulation is reduced. Interference voltages are a further disadvantage; when switching, they can be transmitted by the electronic switches to the microelectrodes and to their connecting leads and can be superimposed on the measuring signal. Such interference voltages negatively influence the measurement result and the signal-to-noise ratio. Interference voltages can exceed the measuring signal many times, therefore their decay must be awaited after switching, before any measurements or stimulation can take place at all. This further reduces the temporal resolution of the microelectrode arrangement.
The number of microelectrodes of known microelectrode arrangements is therefore limited (less than 100 microelectrodes).
It is thus the object of the invention to provide a microelectrode arrangement of the type mentioned in the introduction, with a very large number of microelectrodes which as a result of small dimensions of the microelectrodes and small spacing from each other allows a high local resolution and in addition a high temporal resolution.
This task is solved by the characteristics of claims 1 and 9. Each microelectrode of the microelectrode arrangement accordin
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Dvorak Linda C. M.
NMI Naturwissenschaftliches und Medizinisches Institut
Ruddy David M.
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