Centrifuge Force Microscope Module for Single-Molecule Analysis

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Solution Overview

Problem

Current methods for measuring molecular interactions, such as atomic force microscopes and optical traps, are costly, time-consuming, and limited in their ability to provide detailed, high-throughput measurements of single molecules under controlled mechanical stress, often requiring serial measurements and averaging that obscure rare or fleeting events.

Innovation Solution

A centrifuge force microscope module that integrates an electronics module and optical module within a centrifuge bucket, allowing for the application of centrifugal forces to samples and simultaneous measurement of multiple molecules, enabling high-throughput, parallel, and cost-effective single-molecule force measurements with real-time observation and precise force control.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional single-molecule force probes (AFM, optical traps) are used, then measurement precision is improved, but device complexity and cost increase significantly

Engineering Contradiction:
Improvesingle-molecule measurement capabilityVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical force probe systems (AFM, optical traps) with a centrifugal force-based system. By using centrifugal force generated by rotating the sample container, the system achieves single-molecule force measurements without requiring complex mechanical scanning probes or optical trapping apparatus, thereby reducing device complexity while maintaining measurement precision

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The centrifugal force microscope system is designed to perform multiple functions: it can measure force-dependent kinetics, observe rare events, and characterize molecular interactions under mechanical stress. The same basic apparatus (centrifuge with detection system) can study various types of molecular interactions by simply changing the rotational speed and sample configuration, eliminating the need for multiple specialized instruments

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If serial single-molecule measurements are performed, then measurement precision is improved, but productivity decreases due to time-consuming sequential analysis

Engineering Contradiction:
Improvesingle-molecule measurement accuracyVSAvoidmeasurement throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent combines multiple single-molecule measurements into a single parallel experiment. By attaching multiple ligand-coated beads to a surface and exposing them to receptor molecules simultaneously in a flowing solution, the system performs hundreds of single-molecule force measurements in parallel within one experimental run, dramatically increasing productivity while maintaining the precision of individual molecule analysis

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system uses continuous solution flow to maintain constant replenishment of molecules and remove dissociated complexes, allowing measurements to proceed continuously without interruption. This continuous operation enables high-throughput data collection while maintaining the sensitivity required for single-molecule detection

Inventive Principle:
Principle #20Continuity of useful action

3Productivity

If bulk solution measurements are used, then productivity is improved, but measurement precision decreases due to ensemble averaging that obscures rare events

Engineering Contradiction:
Improvemeasurement efficiencyVSAvoiddetection of rare events
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments the bulk solution into numerous individual measurement sites, each containing single molecules or small numbers of molecules. By attaching ligands to multiple discrete beads distributed across the measurement surface, the system creates many isolated observation points where single-molecule events can be detected individually, preventing ensemble averaging while maintaining high measurement throughput

Inventive Principle:
Principle #1Segmentation

4Ease of operation

If molecular interactions are measured in solution without mechanical stress, then ease of operation is improved, but measurement precision decreases for force-dependent interactions

Engineering Contradiction:
Improvemeasurement simplicityVSAvoidforce-dependent interaction characterization
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The system dynamically controls the mechanical stress applied to molecular interactions by varying the centrifugal force through changes in rotational speed. This allows the same simple apparatus to measure interactions under different force conditions, providing comprehensive characterization of force-dependent kinetics without requiring multiple static measurement setups

Inventive Principle:
Principle #15Dynamics

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

This approach significantly reduces experimental time, enables detailed characterization of molecular interactions, and allows for the study of metastable states and population heterogeneity, providing accurate force-dependent measurements across a wide range of forces and directions, while being more accessible and cost-effective than traditional methods.

Implementation Method 1

measuring a characteristic of a sample under a centrifugal force

Methodology Applied
Scientific EffectCentrifugal force: Centrifugal Force

Implementation Method 2

The optical module is operable to receive and direct light from the sample

Methodology Applied
Scientific EffectLight: Light

Implementation Method 3

at least one optical lens for focusing the light from the sample onto the detector

Methodology Applied
Scientific EffectFocusing: Focusing

Data Source

PatentUS9869851B2Centrifuge force microscope modules and systems for use in a bucket of a centrifuge
Publication Date: 2018.01.16 THE RES FOUNDATION FOR THE STATE UNIV OF NEW YORK
  • US9869851B2 patent drawing
  • US9869851B2 patent drawing
  • US9869851B2 patent drawing

AI summary

A centrifuge force microscope module for use within a bucket of a centrifuge in measuring a characteristic of a sample under a centrifugal force and/or in monitoring a sample under a centrifugal force. The centrifuge force microscope module includes an electronics module and an optical module. The electronics module includes a housing removably disposable in the bucket of the centrifuge, and at least one of a power source and a connector operably connectable to a power source for powering the electronics module. The optical module is operable to receive and direct light from the sample. The optical module is releaseably connectable to the housing of the electronics module.