Optical Force Measurement via Fluorophore Emission Shifts
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Solution Overview
Problem
Current methods for measuring forces on biological structures, such as DNA, are limited by the need for complex equipment and the inability to accurately detect continuous force variations, especially in real-time, due to the requirement for multiple tethers with precisely defined critical forces and the irreversible rupture of tethers.
Innovation Solution
A computer-implemented method using a light-sensitive system to determine forces on biological structures by capturing light information from optically active entities, such as DNA intercalator molecules, which exhibit force-dependent optical properties, allowing for continuous and accurate measurement of forces without the need for complex detection systems or tether rupture.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional force spectroscopy techniques using optical tweezers and calibrated traps are used, then force measurement capability is achieved, but device complexity increases and measurement precision is limited
Solution Approach 1:
The patent replaces mechanical force measurement systems (optical tweezers, calibrated traps, back-focal plane interferometry) with an optical detection system that measures force-induced changes in light properties. Fluorophores or other optically active entities attached to the structure exhibit force-dependent optical signals, eliminating the need for complex mechanical calibration and trap systems while achieving high measurement precision.
Solution Approach 2:
The patent utilizes force-dependent changes in optical properties of fluorophores or optically active entities. The emission intensity, wavelength, or other optical characteristics of these entities change in response to applied force, providing a direct optical readout of force magnitude without requiring mechanical measurement systems.
2Adaptability or versatility
If multiple tethers with precisely defined critical forces are engineered, then force range coverage is improved, but manufacturing precision requirements increase and device complexity increases
Solution Approach 1:
The patent employs optically active entities whose optical parameters (emission intensity, wavelength, lifetime) change in response to force. By selecting entities with different force-response characteristics or attaching multiple entities at different locations, the system can measure forces across a wide range without requiring precisely engineered tethers with specific critical forces, thereby reducing manufacturing precision requirements.
3Reliability
If tether rupture is used to determine force thresholds, then force measurement is achieved, but measurement precision is limited and loss of information occurs
Solution Approach 1:
The patent enables continuous force measurement by monitoring the optical signals of fluorophores or optically active entities that remain intact throughout the measurement process. Unlike tether rupture methods that provide only threshold information, this approach continuously tracks force magnitude through real-time optical signal monitoring, preserving information and improving measurement precision.
4Measurement precision
If conventional camera tracking or fluorescence intensity measurements are used, then elongation measurement is achieved, but measurement precision is limited
Solution Approach 1:
The patent measures elongation and force by detecting force-dependent changes in the optical properties of fluorophores or optically active entities. Changes in emission intensity, wavelength, or other optical characteristics provide direct information about molecular elongation and applied force, simplifying detection compared to conventional camera tracking while improving precision through the sensitivity of optical measurements.
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 precise and continuous measurement of forces on biological structures, including DNA, with enhanced accuracy and the ability to measure varying forces in real-time, using simple experimental setups and general-purpose equipment, without the need for calibrated traps or tether rupture.
Implementation Method 1
The at least part of the structure comprises one or more optically active entities, such as DNA intercalator molecules and donor/acceptor fluorophores. At least one of (i) an optical activity of the entities and (ii) a quantity of the entities depends on the force acting on the at least part of the structure.
Implementation Method 2
The at least part of the structure comprises one or more optically active entities, such as DNA intercalator molecules and donor/acceptor fluorophores
Data Source
AI summary
One aspect of this disclosure relates to a computer-implemented method for determining a force acting on at least part of a structure, for example a biological structure, such as a DNA molecule. The method comprises controlling a light-sensitive system, e.g. of a microscope, to determine light information based on light from the structure. The light is incident on at least a part of the light sensitive system. The light-sensitive system may be said to capture the light from the structure. The at least part of the structure comprises one or more optically active entities, such as DNA intercalator molecules and donor/acceptor fluorophores. At least one of (i) an optical activity of the entities and (ii) a quantity of the entities depends on the force acting on the at least part of the structure. Furthermore, the light information defines a light property value associated with said at least part of the structure. The method further comprises determining the force acting on the at least part of the structure on the basis of said light property value and a reference light property value.