Apparatus for automatically measuring minute membrane potential

Details Apparatus for automatically measuring minute membrane potential Apparatus for automatically measuring minute membrane potential

2000-12-28

2003-03-25

Beisner, William H. (Department: 1744)

Chemistry: molecular biology and microbiology

Apparatus

Including measuring or testing

C435S285200, C204S403130

Reexamination Certificate

active

06537800

ABSTRACT:

TECHNICAL FIELD
The present invention relates to an apparatus for measuring minute membrane potential, which measures a difference in potential between areas separated by a membrane or different positions on a membrane, such as an interior and exterior of a cell membrane, as well as an electrode constituting this apparatus.
BACKGROUND ART
To deal with an aging society, a technical research area for directly supporting human lives is being expanded. This is called a “barrier-free technology” which supports deteriorated or lost functions of human bodies by improving the physical structures of social infrastructures such as towns and houses or developing new personally available equipment. Technical developments based on this concept contribute to creating an environment where human beings live easy social lives whether or not they are physically handicapped.
The barrier-free technology initially concentrated on electronics, machinery, and construction but is being gradually expanded; some recent studies for the barrier-free technology are directly related to medicine. Typical examples include research on advanced medical equipment such as functional artificial hands or legs which supplement the functions of the bodies of handicapped people or the like. Such equipment is now controlled using methods such as electromyographic detection or detection of motions of the eyes or tongue, but information obtained by these input means is quantitatively significantly insufficient in terms of the amount of information required for motor and sensory functions of living bodies. If, for example, a person has lost his hand or leg due to a traffic accident, or a war wound, he must have an artificial hand or leg. However, to control the operation of the artificial hand or leg as if it were an actual hand or leg and to feed back senses for temperature or contacts to the human body, a certain interface is required which can simultaneously measure action potential generated by individual nerves of a bundle of several hundred peripheral nerves and then input a corresponding signal. Already developed such interfaces, however, are all insufficient.
One of the most successful examples in the field of direct exchange of information between nerves and electronic equipment is equipment called artificial inner ear [Rehabilitation Medicine, 31, 233-239 (1994)]. If an auditory defect occurs such that a portion between the tympanic membrane and the inner ear is prevented from functioning, the artificial inner ear executes the function of this portion by directly stimulating auditory nerves in the cochlear organ. The artificial inner ear processes a sound input through a microphone depending on the auditory characteristic of this person to generate a digital signal in order to electrically stimulate terminals of the auditory nerves, that is, cochlear nerves. Spherical electrodes are generally arranged at about 22 locations inside the cochlea, where about 30,000 auditory nerves are located, to input a sound signal to the nerves through the electrodes. For some time after the artificial inner ear has been implanted, most subjects feel that they hear very strange sounds, but once information processing in the brain has been adapted to the artificial inner ear, the subjects can distinguish sounds. Analysis and improvements of electrodes for the artificial inner ear is a large research area.
A substantial reduction in input auditory information from an inherent input through 30,000 nerves to an artificial input through about 22 electrodes means that auditory information received by the brain also decreases down to 0.1% or less. Thus, regeneration of the sound listening ability depends on whether the brain can supplement and understand a substantially reduced amount of information. Several months are required to optimally adapt the auditory processing function of the brain to the artificial inner ear. The artificial inner ear suggests possibilities of nerve interfaces.
With the artificial inner ear, however, the electrodes are installed in the cochlear organ, where nerve terminals are exposed and lie over several centimeters. The nerve stimulating electrodes may be installed at nerve terminals exposed to the interior of the organ, so that it is not physically difficult to arrange the electrodes. In addition, in inputting a sound signal, it is very easy to analyze and determine those of the nerves which receive the signal and the frequency of the signal that can be received by these nerves. In this manner, the reasons why the artificial inner ear has successfully been put to practical use include many appropriate conditions for transmission of signals to the nerves through the electrodes. In other words, it is virtually impossible to directly apply the electrode technology for the artificial inner ear to nerves other than the cochlear nerves.
Many research institutes in the world are developing interfaces for exchanging information between nerve cells and electronic equipment; these studies can be roughly classified into two aspects.
One of them is a medical technological approach where minute electrodes are implanted in a nerve bundle or the brain [IEEE Trans. Biomed. Eng., 39, 893-902 (1992)] [IEEE Trans. Biomed. Eng. 41, 567-577 (1994)] [IEEE Trans. Biomed. Eng., 41, 305-313 (1994)]. This approach attempts to provide terminals for obtaining a control signal for rehabilitation equipment directly from nerves or multichannel connection terminals for inputting a signal to nerves.
The other aspect is based on a long-term prospect for application of the information processing ability of nerve cells to computers [Bioelectrochemistry and Bioenergetics, 29, 193-204 (1992)] [Brain Research, 446, 189-194 (1988)]. This approach pursues the possibilities of what is called “biocomputers” that use living cells as operation elements.
Conventional nerve interfaces are roughly classified into the following three types:
(a) Aggregate needle-shaped metal electrodes and needle point holder-shaped aggregate metal needle electrodes [IEEE Trans. Biomed. Eng., 41, 1136-1146 (1994)]
(b) Axon regenerated matrix electrodes [IEEE Trans. Biomed. Eng., 39, 893-902 (1992)] [IEEE Trans. Biomed. Eng., 41, 567-577 (1994)] [IEEE Trans. Biomed. End., 41, 305-313 (1994)]
Flat cultured-nerve-cell electrodes on a substrate [Bioelectrochemistry and Bioenergetics, 29, 193-204 (1992)] [Brain Research, 446, 189-194]
Needle-shaped electrodes for measuring nerves have been used since the initial period of research on nerves, but the study of microneurography was the first to record the action potential of a single human peripheral nerve in situ [Clinical Electroencephalogram, 25, 493-500, 564-571, 629-638 (1983)]. The needle point holder-shaped electrode is one of the aggregate types in which this electrode is formed at a tip of a needle or on a side thereof and which is struck to a severed nerve bundle or a tissue in the brain [IEEE Trans. Biomed. Eng., 41, 1136-1146 (1994)]. That is, the needle point holder-shaped electrode is obtained by three-dimensionally expanding the needle-shaped electrode using a micromachine technology. In a basic design, the needle-shaped electrode records a faint extracellular current from a nerve that is accidentally located close to the electrode section. Although the needle-shaped electrode can be used to measure a single nerve cell, this method is evidently not accurate enough to simultaneously measure a large number of nerves even if the degree of integration of needle-shaped electrodes is increased to enhance spatial resolution, because the relative distance between each nerve and the electrode depends on accidents.
The axon regenerated matrix electrode in 2 is a field that has been expanded since 1992 when Stanford University conducted a relevant study, and many reports have recently been made on this electrode [IEEE Trans. Biomed. Eng. 39, 893-902 (1992)] [IEEE Trans. Bi

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