Semiconductor for measuring biological interactions
Inventors
Rasooly, Avraham • Yang, Minghui • Bruck, Hugh A. • Kostov, Yordan
Assignees
University of Maryland Baltimore County UMBC • University of Maryland College Park • US Department of Health and Human Services
Publication Number
US-8614466-B2
Publication Date
2013-12-24
Expiration Date
2029-11-18
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Abstract
An apparatus and method are disclosed for electrically directly detecting biomolecular binding in a semiconductor. The semiconductor can be based on electrical percolation of nanomaterial formed in the gate region. In one embodiment of an apparatus, a semiconductor includes first and second electrodes with a gate region there between. The gate region includes a multilayered matrix of electrically conductive material with capture molecules for binding target molecules, such as antibody, receptors, DNA, RNA, peptides and aptamer. The molecular interactions between the capture molecules and the target molecules disrupts the matrix's continuity resulting in a change in electrical resistance, capacitance or impedance. The increase in resistance, capacitance or impedance can be directly measured electronically, without the need for optical sensors or labels. The multi-layered matrix can be formed from a plurality of single-walled nanotubes, graphene, or buckeyballs or any kind of conductive nanowire, such as metal nanowires or nanowires made from conductive polymers.
Core Innovation
An apparatus and method are disclosed for electrically detecting biomolecular binding in a semiconductor, leveraging a physical principle called electrical percolation. The device includes first and second electrodes with a gate region between them, where the gate region is a multi-layered three-dimensional matrix of electrically conductive material with capture biomolecules. Binding between capture biomolecules and target biomolecules disrupts the network's continuity, causing measurable changes in electrical resistance, capacitance, or impedance. These changes can be directly detected electronically without optical sensors or labels.
The multi-layered matrix can be formed from nanomaterials such as single-walled carbon nanotubes, graphene, buckyballs, metallic nanowires, or conductive polymer nanowires. The semiconductor is fabricated near the percolation threshold so that small molecular interactions cause large changes in conductivity, thereby increasing detection sensitivity. This approach contrasts with prior field-effect transistor (FET) designs that require complex fabrication and on-chip nanowire synthesis.
The problem being solved stems from limitations of existing biosensors, particularly FET-based devices using single- or submonolayer carbon nanotubes. Such devices require complex, expensive, and specialized chemical vapor deposition fabrication methods unsuitable for multi-FET chip fabrication. The disclosed invention addresses the need for a biological semiconductor that is simpler, lower cost, and easily fabricated, especially for multi-gate devices, while maintaining sensitivity and supporting multi-analyte detection.
Claims Coverage
The patent includes independent claims directed to the semiconductor device structure, methods for detecting molecular interactions using the semiconductor, a system incorporating the semiconductor for detection, and methods of manufacturing the semiconductor. There are five independent claims illustrating inventive features related to device architecture, detection method, system integration, and fabrication processes.
Three-dimensional matrix with capture biomolecules disrupting electrical continuity
The semiconductor includes first and second electrodes with a gate region made of a three-dimensional matrix of electrical conductors having capture biomolecules bound within the matrix. Molecular binding between capture biomolecules and target molecules disrupts the three-dimensional electrical network, severing some conductors and modulating resistivity, impedance, or capacitance.
Method for detecting molecular interactions by resistance measurement
A method using the semiconductor comprising applying a specimen with target molecules to the gate region and automatically measuring resistance between electrodes to detect binding events. The method includes comparing measured resistance to control measurements to quantify target molecule binding.
System for detecting molecular interactions with automated specimen delivery and monitoring
A system comprising the semiconductor with a three-dimensional network and capture biomolecules, a resistivity measurement device coupled to the electrodes, a computer for continuous monitoring, and valves controlled by the computer to supply specimens automatically to the gate region.
Manufacturing method using immobilized capture biomolecules on multilayered electrical conductors
A method of manufacturing the semiconductor by providing a multilayered electrical conductor material, immobilizing capture biomolecules via electrostatic absorption to form a solution, depositing this solution into a well to form the gate region, and then depositing electrode material at opposing ends.
The independent claims encompass the semiconductor device featuring a three-dimensional matrix with capture biomolecules that modulate electrical properties upon molecular binding, methods for detecting such interactions via resistance measurements, automated systems integrating specimen delivery and measurement, and manufacturing approaches enabling simple fabrication with immobilized biomolecules in multilayered conductor networks.
Stated Advantages
Supports simultaneous multi-sample or multi-target analysis on the same chip, enabling multiplexed biomolecular detection.
Does not require specialized fabrication facilities or expertise, reducing cost and broadening practical applications.
Offers long-term stability allowing storage for extended periods before use.
Enables fast, continuous, and near-instantaneous detection of biological interactions.
Documented Applications
Scientific, medical, and industrial applications for directly measuring biological interactions such as protein-protein interactions, DNA-protein binding, nucleic acid binding, and hormone-receptor binding.
Detection of biochemical analytes including antibodies, antigens, nucleic acids, peptides, hormones, and small molecule analytes in liquid biological samples such as blood, serum, saliva, urine, and other fluids.
Food safety testing, demonstrated by detection of staphylococcal enterotoxin B (SEB) in food matrices with partial sample purification to reduce background.
Biosensing platforms for multi-analyte detection, forming basis for biological central processing units capable of processing and sorting multiple biological signals simultaneously.
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