Active solid-state devices (e.g. – transistors – solid-state diode – Field effect device – Having insulated electrode
Reexamination Certificate
2001-08-22
2004-03-09
Abraham, Fetsum (Department: 2826)
Active solid-state devices (e.g., transistors, solid-state diode
Field effect device
Having insulated electrode
Reexamination Certificate
active
06703660
ABSTRACT:
FIELD OF THE INVENTION
This invention is generally in the field of bio-molecular electronics, and relates to electrical devices with biological components.
BACKGROUND OF THE INVENTION
The following publications are believed to be relevant to the Background section of the specification.
1. Fromherz, P., “Interfacing Neurons and Silicon by Electrical Induction”,
Ber. Bunsenges. Phys. Chem.,
100:1093-1102 (1996).
2. Stett, A., Mÿller, B., Fromherz, P., “Two-way Neuron-Silicon Interface by Electrical Induction”, “
Phys. Rev. B.,
55:1779-1781 (1997).
3. Offenhaussser, A., et. al., “Neuronal Cells Cultured on Modified Microelectronic Device Surfaces”,
J. Vac. Soc. Technol. A.,
13(5):2606-2612 (1995).
4. Potomber, R. S., Matsuzawa, M., Leisi, P., “Conducting Networks from Cultured Cells on Self-assembled Monolayers”,
Synthetic Metals”,
71, 1997 (1995).
5. Stett, A., Mÿller, B., Fromherz, P., “Two-way Neuron-Silicon Interface by Electrical Induction”, “
Phys. Rev. B.,
55:1779-1781 (1997).
6. Matsuzawa, M., Umemura, K., Beyer, D., Sugioka, K., Knoll, W., “Micropatterning of Neurons using Organic Substances in Culture”,
Thin Solid Films,
305:74-79 (1997).
7. Dulcey, C. S., Georger, J. H., Krauthamer, V., Stenger, D. A., Fare, T. L., Calvert, J. M.,
Science,
252:551 (1991).
8. (a) Cohen, R., Zenou, N., Cahen, D., Yitchaik, S., “Molecular Electronic Tuning of Si Surfaces”
Chem. Phys. Lett.,
279:270-274 (1997);
(b) Zenou, N., Zelichenok, A., Yitzchaik, S., Cohen, R., Cahen, D., “Tuning the electronic properties of silicon via molecular self-assembly” in “Thin Organic Films”, C. W. Frank—Ed,
ACS Symp. Ser.,
695:57-66 (1998).
9. Yitzchaik, S., Marks, T. J., “Chromophoric Self-Assembled Superlattices”,
Acc. Chem. Res.,
29:197-202 (1996) and references therein.
10. 08/857,769 of May 1997.
11. U.S. Pat. No. 5,156,918.
12. Surplice, N. A.; D'Archy, R. J. J. Phys. E: Sc. Instr. 1970, 3, 477-482.
Interaction between neurons and electronic devices have been in existence for several decades for a plurality of purposes. During the past decades, these interactions were usually achieved by inserting an electrode or an array of electrodes into the neurons or placing an electrode or an array of electrodes in the vicinity of the neurons' membranes so as to detect voltage changes. The detection electrode or array of electrodes can also be used for the stimulation of neurons.
With the growing body of knowledge concerning transistors and semi-conductors there have been several attempts directed at the coupling the two types of information flow: electron conduction in solids (achieved by the transistor), and ion conduction in aqueous environments (carried out by the neurons). However, the coupling between the transistors and the neurons suffered from a series of problems including basic scientific problems as well as technological difficulties. Direct coupling of neurons to enhancement type MOS transistors requires the application of a DC bias between the biological solution and the transistor substrate in order to create a conducting channel. The combination of the DC bias, the biological ionic solution and the transistor, is a potential source for a series of degradation processes resulting from leakage currents, heat generation, electrochemical corrosion and ionic drift instabilities. All this will eventually lead to damage of the neuron and/or the transistor.
The publication of Stett et al. (Ref. 2) describes a nerve cell which is placed on a combined microstructure of an insulated spot of doped silicon and an insulated-gate field effect transistor. The neuron was placed on the transistor without any adhesive material. Voltage pulses are applied by the insulated spot to the neuron through capacitive coupling. They elicit neuronal activity which in turn can be detected by the transistor. The article describes a bi-directional interface between the ionics of the neuron and the electronics of the silicon, achieved by two separate modalities. Here, however two separate locations on the silicon chip spaced-apart in a horizontal plane are used, namely, one for sensing of neuronal activity achieved by an insulated-gate field effect transistor, and the other for capacitive simulation of neuron activity achieved by an insulated spot of doped silicon. This approach of two separate locations, one for the neuron activation and one for sensing its activity, imposes several limitations in multi neuron multi transistor systems, as follows:
it requires accurate positioning of each neuron on the electronic circuit;
it increases the number of electronic connections to a given neuron system; and
it requires larger area of the electronic system.
It is highly desirable to provide coupling between neurons, (and other voltage sensitive cells) and electrical devices both for the purpose of detecting electrical activity in these cells, and for stimulating the cells via said electrical devices. The coupling should be such which allows the detection and stimulation by use of a relatively simple electronic structure, and in addition, the electrical structure should be bio-compatible and the mode of its coupling should be such as not to produce the electrochemical changes and toxic substances which are harmful to live cells.
The term “chemical synapses”, refers to a junction between two neurons wherein the axon terminals of a pre-synaptic cell, containing a vesicle filled with a particular neurotransmitter substance, are in close vicinity to the membranes of a post synaptic cell. When the nerve impulse reaches the axon terminal the vesicles are exocytosed releasing their neurotransmitter components into the synaptic cleft which is the narrow space between the pre-synaptic and the post synaptic cell. The transmitter diffuses across the synaptic cleft, and then binds to receptors on the post synaptic cells. Upon binding, the neurontransmitter induces a change in the ionic permeability of the post synaptic membrane that results in the disturbance of the electrical potential at this point. If the electrical disturbance is sufficiently high it can induce an action potential, or a muscle contraction (where the cell is a muscle), or alternatively, may be sufficient to trigger release of hormones from gland cells.
Although the chemical synapse site is a major component in the modulation of neuronal activity, said modulation effecting properties such as memory, learning, degradation due to various neurodegenerative diseases, the physiological phenomena of the synapse was studied and utilized mainly in biological systems.
Possible means for communication between nerve cells and transistors may be polarizable molecules. Such molecules are described in Ref. 9. Furthermore, U.S. patent application Ser. No. 08/857,769, May 1997, and U.S. Pat. No. 5,156,918 concern methods for forming a polymeric structure composed of two or more discrete monolayers wherein at least one layer is composed of polycyclic aromatic molecules with a defined Z-axis oriented substantially normal to the plane or at an angle close to normal, up to ca. 45°. Ref. 8 further addresses the effects of polarizable molecules on the electronic properties of silicon.
Glossary
“Voltage sensitive cell (VSC)”—a cell in which normal physiological activity is modulated by voltage changes across its membrane. Typical examples are neurons, muscle cells and cells of glands which secrete hormones as a result of voltage change.
“Electrical junction”—a functional connection between a single transistor and at least one VSC enabling signal transfer in at least one direction, either from the transistor to the VSC, or from the VSC to the transistor through capacitive coupling.
“DC bias”—the voltage applied between the biological solution in which the VSC is embedded and the transistor substrate, which sets the transistor ready for sensing the VSC activity (i.e., “opens” the transistor).
“External surface of the transistor”—the outer surface of an uppermost, insulating layer covering the active component of the transistor.
“Binding moieties”—refers to molecules which may
Shappir Joseph
Spira Micha
Yitzchaik Shlomo
Abraham Fetsum
Browdy and Neimark , P.L.L.C.
Yissum Research Development Company of the Hebrew University of
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