Method for identifying biochemical and chemical reactions and micromechanical processes using nanomechanical and electronic signal identification
First Claim
1. 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.
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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.
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Citations
19 Claims
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1. 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:
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(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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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13. 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:
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(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. - View Dependent Claims (14, 15, 16, 17, 18)
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19. 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:
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(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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Specification