# US 7,407,814 B2 · Active NEMS arrays for biochemical analyses > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,407,814 B2 - Document ID: US7407814B2 - Status: Granted - Kind: B2 - Application number: 09/927,779 - Filed: 2001-08-09 - Published: 2002-11-14 - Granted: 2008-08-05 - Earliest claimed: 2000-08-09 - Assignees: California Institute of Technology - Inventors: Michael L. Roukes; Scott E. Fraser; Jerry E. Solomon; Michael C. Cross - Web page: https://patentgrep.com/patent/US7407814B2 ## CPC - G01N 29/036: by measuring frequency or resonance of acoustic waves - G01N 33/54373: {involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings} - B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery - B82Y 35/00: Methods or apparatus for measurement or analysis of nanostructures - G01N 2291/0257: with a layer containing at least one organic compound - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES ## Abstract A biofunctionalized nanoelectromechanical device (BioNEMS) for sensing single-molecules in solution by measuring the variation in the mechanical displacement of the BioNEMS device during a binding event is provided. The biofunctionalized nanoelectromechanical device according to the invention generally comprises a nanomechanical mechanical resonator, a detector integral with the mechanical resonator for measuring the mechanical displacement of the resonator, and electronics connected to the detector for communicating the results to a user. A system of biofunctionalized nanoelectromechanical devices and a method for utilizing the biofunctionalized nanoelectromechanical device of the present invention are also provided. ## Claims ### Claim 1 A molecular detector capable of detecting an analyte in solution comprising: a solution reservoir; at least one first nanometer-scale mechanical resonator which is disposed within the reservoir, wherein the at least one first resonator is biofunctionalized with a first receptor or a first ligand; a substrate or a second mechanical resonator which is disposed within the reservoir, wherein the substrate or the second resonator is biofunctionalized with a second receptor or a second ligand, and wherein the first receptor or ligand and the second receptor or ligand are capable of binding to the analyte in solution such that the analyte binds to both the first receptor or ligand and to the second receptor or ligand at a same time; and a detector in signal communication with the at least one first resonator for measuring a mechanical displacement of the resonator for detection of the analyte. ### Claim 2 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator comprises a resonator selected from the group consisting of: vibrational resonators, rotational resonators, torsional resonators and composite resonators. ### Claim 3 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator is a notched vibrational cantilever. ### Claim 4 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator is biofunctionalized with the first receptor. ### Claim 5 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator is made from a material selected from the group consisting of: silicon oxide, silicon, silicon carbide and gallium arsenide. ### Claim 6 (depends on 1) A molecular detector as described in claim 1, wherein the detector is integral with the at least one first resonator. ### Claim 7 (depends on 1) A molecular detector as described in claim 1, wherein the detector is a piezoresistive transducer. ### Claim 8 (depends on 7) A molecular detector as described in claim 7, wherein the transducer is made of p+ doped silicon. ### Claim 9 (depends on 1) A molecular detector as described in claim 1, wherein the detector is an optical detector. ### Claim 10 (depends on 1) A molecular detector as described in claim 1, wherein the detector is a lock-in detector. ### Claim 11 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator has a thickness between about 10 nm and 1 μm, a width between about 10 nm and 1 μm, and a length between about 1 μm and 10 μm. ### Claim 12 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator has a resonance motion vacuum frequency between about 0.1 and 12 MHz. ### Claim 13 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator has a force constant between about 0.1 mN/m and 1 N/m. ### Claim 14 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator has a Reynolds number between about 0.00 1 and 2.0. ### Claim 15 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator has a mass loading coefficient between about 0.3 and 11. ### Claim 16 (depends on 1) A molecular detector as described in claim 1, having a force sensitivity of about 8fN/√Hz or greater. ### Claim 17 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator is biofunctionalized to detect a receptor/ligand interaction. ### Claim 18 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator is biofunctionalized to detect DNA hybridization. ### Claim 19 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator is biofunctionalized to detect a chemical bond. ### Claim 20 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator is biofunctionalized to detect protein unfolding. ### Claim 21 (depends on 1) A molecular detector as described in claim 1, wherein the detector is a detector which is adapted to measure a change in damping of resonance motion of the at least one first resonator in response to a molecular binding event on the at least one first resonator. ### Claim 22 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator comprises a cantilever having at least two dimensions of one micron or less. ### Claim 23 (depends on 1) A molecular detector as described in claim 1, wherein the at least one first resonator is biofunctionalized with the first receptor and the substrate is biofunctionalized with the second ligand. ### Claim 24 (depends on 1) A molecular detector as described in claim 1, further comprising a driving element capable of mechanically displacing the first resonator at a chosen frequency. ### Claim 25 (depends on 1) A molecular detector as described in claim 1, wherein the detector comprises a piezoresistive detector layer which is located on the at least one resonator. ### Claim 26 (depends on 1) A molecular detector as described in claim 1, wherein the substrate is disposed in the reservoir.