Multi-Agent AFM Probe for Simultaneous Molecular Mapping
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Solution Overview
Problem
Current atomic force microscopes (AFMs) are limited in differentiating between molecular targets of the same molecular weight and determining the relative spatial arrangement of multiple chemical entities in complex samples, as they can only detect one target per image, making it difficult to analyze the spatial relationship between different participants in biological processes.
Innovation Solution
An AFM with a scanning probe that oscillates with a low mechanical Q factor and is sensitive to multiple properties of a surface, equipped with two or more sensing agents tethered to the tip, allowing for simultaneous recording of topographic and recognition data to map the location of multiple targets, and a method to remove and re-image with different sensing agents to determine relative locations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If a single sensing agent is used on the probe tip, then the system can detect one target type, but it cannot determine the relative spatial arrangement of multiple chemical entities
Solution Approach 1:
The patent combines multiple sensing agents (e.g., different antibodies or receptor proteins) on a single probe tip to simultaneously detect multiple target molecules. This merging approach enables the probe to recognize and map the spatial arrangement of different chemical entities in one imaging operation, resolving the contradiction between detecting multiple targets and maintaining simple probe configuration.
Solution Approach 2:
The probe tip is designed with multi-functionality by attaching multiple types of sensing agents that can recognize different target molecules. This universal probe configuration allows a single probe to perform multiple detection functions across different target types, eliminating the need for separate probes for each target and enabling simultaneous multi-target detection with spatial information.
2Measurement precision
If the probe tip is changed to detect a different target, then a second image can be recorded, but the time required makes it difficult to determine relative locations
Solution Approach 1:
By merging multiple sensing agents onto a single probe tip, the system can simultaneously detect multiple target types in one imaging session. This eliminates the need to change probes between different targets, thereby eliminating the time loss associated with probe changes while maintaining precise spatial information about the relative positions of all detected targets.
Solution Approach 2:
The multi-sensing agent probe enables continuous detection of multiple targets without interruption for probe changes. The useful action of detecting different target types can proceed continuously in a single imaging operation, eliminating the discontinuities and time delays inherent in sequential probe changes, thus preserving spatial relationship information.
3Loss of information
If statistical analysis is used to estimate relative positions from separate images, then computational complexity increases, but the results remain only estimated rather than definitive
Solution Approach 1:
The patent merges the detection of multiple target types into a single imaging operation, capturing spatial relationship information directly during the imaging process itself. This approach eliminates the need for subsequent statistical analysis of separate images, as the relative positions are directly recorded in the single image containing all target types simultaneously, thereby avoiding both computational complexity and estimation limitations.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables high spatial resolution imaging of multiple targets and their relative positions, providing rapid quantitative measurement of molecular binding and improving the analysis of complex biological systems by allowing simultaneous detection and mapping of multiple targets.
Implementation Method 1
The antibody tethered to an oscillating AFM sensing probe, binds to its antigen and changes the pattern of oscillation as the probe is scanned over the surface
Implementation Method 2
The sensing agent 102 binds to a target on the surface 103
Data Source
AI summary
An atomic force microscope and a method for detecting interactions between a probe and two or more sensed agents on a scanned surface and determining the relative location of two or more sensed agents is provided. The microscope has a scanning probe with a tip that is sensitive to two or more sensed agents on said scanned surface; two or more sensing agents tethered to the tip of the probe; and a device for recording the displacement of said probe tip as a function of time, topographic images, and the spatial location of interactions between said probe and the two or more sensed agents on said surface.