US5620854A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Method for identifying biochemical and chemical reactions and micromechanical processes using nanomechanical and electronic signal identification
Assignee: University of California, San Diego
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Filing: 1995-03-13
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Granted: 1997-04-15
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Expires: 2015-03-13
Abstract
Abstract A scanning probe microscope, such as an atomic force microscope (AFM) or a scanning tunneling microscope (STM), is operated in a stationary mode on a site where an activity of interest occurs to measure and identify characteristic time-varying micromotions caused by biological, chemical, mechanical, electrical, optical, or physical processes. The tip and cantilever assembly of an AFM is used as a micromechanical detector of characteristic micromotions transmitted either directly by a site of interest or indirectly through the surrounding medium. Alternatively, the exponential dependence of the tunneling current on the size of the gap in the STM is used to detect micromechanical movement. The stationary mode of operation can be used to observe dynamic biological processes in real time and in a natural environment, such as polymerase processing of DNA for determining the sequence of a DNA molecule.
Inventors
- 👤 John F. Holzrichter
- 👤 Wigbert J. Siekhaus
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 18:04
CPC Classifications
G; G01; G01Q; G01Q60/00; G01Q60/24; G01Q60/38; G01Q60/42; B; B82; B82Y; B82Y35/00; C; C12; C12Q; C12Q1/00; C12Q1/68; C12Q1/6869; G01Q60/02; G01Q60/04; Y; Y10; Y10S; Y10S977/00; Y10S977/84; Y10S977/849; Y10S977/852; Y10S977/853
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
121 words
A method for detecting time-varying motions created on a microscopic scale using a scanning probe microscope having a physical tip for mechanical signal identification, comprising: (a) locating a single site comprising a molecule or molecules of interest having microscopic dimensions by using the scanning probe microscope in a locator mode, wherein the molecule or molecules have time-varying motions due to a biological, chemical, mechanical, optical, or electrical process; (b) positioning the physical tip of the scanning probe microscope in a stationary mode at the single site; and (c) monitoring physical movements of the tip as a function of time as the process occurs by using the scanning probe microscope in a stationary, non-scanning mode, thereby detecting micromotions created at the site.
Claim 2
Independent Claim
121 words
A method for detecting time-varying motions created on a microscopic scale using a scanning probe microscope having a physical tip for mechanical signal identification, comprising: (a) locating a single site comprising a molecule or molecules of interest having microscopic dimensions by using the scanning probe microscope in a locator mode, wherein the molecule or molecules have time-varying motions due to a biological, chemical, mechanical, optical, or electrical process; (b) positioning the physical tip of the scanning probe microscope in a stationary mode at the single site; and (c) monitoring physical movements of the tip as a function of time as the process occurs by using the scanning probe microscope in a stationary, non-scanning mode, thereby detecting micromotions created at the site.
Claim 3
Dependent Claim
38 words
The method as recited in claim 1, further comprising positioning the tip in physical contact with at least one molecule at the site, and wherein the physical movements of the tip are caused by micromotions of the molecule.
Claim 4
Dependent Claim
55 words
The method as recited in claim 1, further comprising surrounding the site with a transmitting medium, and positioning the tip in physical contact with the medium, wherein the micromotions created at the site are transmitted through the medium as acoustic or pressure waves, and the physical movements of the tip are caused by the waves.
Claim 5
Dependent Claim
21 words
The method as recited in claim 1, further comprising attaching at least one molecule at the site to a supporting substrate.
Claim 6
Dependent Claim
26 words
The method as recited in claim 1, wherein the scanning probe microscope is selected from the group consisting of atomic force microscopes and scanning tunneling microscopes.
Claim 7
Dependent Claim
54 words
The method as recited in claim 1, further comprising attaching an intermediary body to at least one molecule at a site of interest, whereby the micromotions of the site of interest cause micromotions at the intermediary body, and wherein the physical movements of the tip are caused by micromotions created at the intermediary body.
Claim 8
Dependent Claim
35 words
The method as recited in claim 6, further comprising positioning the tip in physical contact with the intermediary body, and wherein the physical movements of the tip are caused by micromotions of the intermediary body.
Claim 9
Dependent Claim
57 words
The method as recited in claim 6, further comprising surrounding the intermediary body with a transmitting medium, and positioning the tip in physical contact with the medium, wherein the micromotions created at the intermediary body are transmitted through the medium as acoustic or pressure waves, and the physical movements of the tip are caused by the waves.
Claim 10
Dependent Claim
26 words
The method as recited in claim 6, wherein the intermediary body is selected from the group consisting of a membrane and a chemically inert metallic sphere.
Claim 11
Dependent Claim
16 words
The method as recited in claim 1, wherein the tip comprises a tip and cantilever assembly.
Claim 12
Dependent Claim
16 words
The method as recited in claim 1, wherein the site is an enzyme having polymerase activity.
Claim 13
Dependent Claim
14 words
The method as recited in claim 1, wherein the site is a living cell.
Claim 14
Independent Claim
136 words
A method for detecting time-varying motions created on a microscopic scale by an enzyme using a scanning probe microscope having a physical tip for mechanical signal identification, comprising: (a) attaching an enzyme to a supporting matrix, wherein the enzyme is in solution and has time-varying micromotions due to interaction with a substrate; (b) locating the enzyme and positioning the physical tip of the scanning probe microscope in a stationary mode at the enzyme; (c) introducing the substrate into the solution, wherein the solution is allowed to come to rest and the substrate and the enzyme interact; and (d) monitoring the physical movements of the tip as a function of time as the interaction occurs, by using the scanning probe microscope in a stationary, non-scanning mode, thereby detecting micromotions caused by the enzyme's interaction with the substrate.
Claim 15
Independent Claim
136 words
A method for detecting time-varying motions created on a microscopic scale by an enzyme using a scanning probe microscope having a physical tip for mechanical signal identification, comprising: (a) attaching an enzyme to a supporting matrix, wherein the enzyme is in solution and has time-varying micromotions due to interaction with a substrate; (b) locating the enzyme and positioning the physical tip of the scanning probe microscope in a stationary mode at the enzyme; (c) introducing the substrate into the solution, wherein the solution is allowed to come to rest and the substrate and the enzyme interact; and (d) monitoring the physical movements of the tip as a function of time as the interaction occurs, by using the scanning probe microscope in a stationary, non-scanning mode, thereby detecting micromotions caused by the enzyme's interaction with the substrate.
Claim 16
Dependent Claim
33 words
The method as recited in claim 13, further comprising positioning the tip in physical contact with the enzyme, and wherein the physical movements of the tip are caused by micromotions of the enzyme.
Claim 17
Dependent Claim
55 words
The method as recited in claim 13, further comprising surrounding the enzyme with a transmitting medium, and positioning the tip in physical contact with the medium, wherein the micromotions created at the enzyme are transmitted through the medium as acoustic or pressure waves, and the physical movements of the tip are caused by the waves.
Claim 18
Dependent Claim
45 words
The method as recited in claim 13, further comprising attaching an intermediary body to the enzyme, whereby the micromotions of the enzyme cause micromotions at the intermediary body, and wherein the physical movements of the tip are caused by micromotions created at the intermediary body.
Claim 19
Dependent Claim
34 words
The method as recited in claim 16, further comprising positioning the tip in physical contact with the intermediary body, and the physical movements of the tip are caused by micromotions of the intermediary body.
Claim 20
Dependent Claim
57 words
The method as recited in claim 16, further comprising surrounding the intermediary body with a transmitting medium, and positioning the tip in physical contact with the medium, wherein the micromotions created at the intermediary body are transmitted through the medium as acoustic or pressure waves, and the physical movements of the tip are caused by the waves.
Claim 21
Independent Claim
119 words
A method for detecting time-varying motions created on a microscopic scale using a scanning probe microscope having a physical tip for mechanical signal identification, comprising: (a) locating a single site comprising a molecule or molecules of interest having microscopic dimensions by using the scanning probe microscope in a locator mode, wherein the molecule or molecules have time-varying motions due to a biological, chemical, mechanical, optical, or electrical process; (b) attaching an intermediary body to the site of interest, whereby micromotions of the site of interest cause micromotions at the intermediary body; and (c) monitoring the physical movements of the intermediary as a function of time as the process occurs using laser interferometry, thereby detecting micromotions created at the site.
Claim 22
Independent Claim
119 words
A method for detecting time-varying motions created on a microscopic scale using a scanning probe microscope having a physical tip for mechanical signal identification, comprising: (a) locating a single site comprising a molecule or molecules of interest having microscopic dimensions by using the scanning probe microscope in a locator mode, wherein the molecule or molecules have time-varying motions due to a biological, chemical, mechanical, optical, or electrical process; (b) attaching an intermediary body to the site of interest, whereby micromotions of the site of interest cause micromotions at the intermediary body; and (c) monitoring the physical movements of the intermediary as a function of time as the process occurs using laser interferometry, thereby detecting micromotions created at the site.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-04-14 | 2000-10-14 | 2001-04-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-04-14 | 2004-10-14 | 2005-04-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-04-14 | 2008-10-14 | 2009-04-15 | $7700.00 | Window Closed / Lapsed |