Nanopore Detection with Optical Trapping and Carrier Beads
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Solution Overview
Problem
Current nanopore devices face inefficiencies in delivering target molecules to the detection area, limiting throughput and detection sensitivity, especially for biomarkers at ultra-low concentrations, such as femto- to atto-molar ranges.
Innovation Solution
A chip-based system using microscale carrier beads to concentrate and optically trap target molecules near a nanopore, enhancing local analyte concentration by up to six orders of magnitude and improving capture rates through solid-phase extraction and microfluidic processing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If target molecules are delivered to nanopore using bulk solution methods, then the system is simple to operate, but the capture rate and detection sensitivity are limited
Solution Approach 1:
The system divides the sample processing into distinct functional modules: microfluidic channels for fluid transport, optical trapping zones for particle concentration, and nanopore detection regions. This segmentation allows each component to be optimized independently while maintaining overall system functionality and detection sensitivity.
Solution Approach 2:
Microscale carrier beads serve as intermediaries that concentrate target molecules and deliver them to the nanopore. These beads act as a mediator between the bulk solution and the nanopore detection system, enhancing local analyte concentration by up to six orders of magnitude without requiring direct manipulation of individual target molecules.
2Productivity
If microscale carrier beads are used to concentrate target molecules, then the local analyte concentration increases by up to six orders of magnitude, but the device complexity increases
Solution Approach 1:
The system replaces mechanical pumping and complex fluid handling with optical trapping forces to concentrate and deliver carrier beads to the nanopore. This substitution of mechanical systems with optical fields simplifies the overall device architecture while achieving high capture rates through non-contact manipulation.
Solution Approach 2:
The system utilizes changes in optical field parameters (intensity, gradient) to control the concentration and delivery of carrier beads. By modulating optical trap strength and positioning, the system dynamically adjusts particle concentration at the nanopore to optimize capture rate without mechanical intervention.
3Productivity
If optical trapping is used to deliver carrier beads to nanopore, then the throughput and limit of detection are enhanced, but the energy consumption increases
Solution Approach 1:
The system employs periodic optical trapping and release cycles to deliver carrier beads to the nanopore in controlled bursts. This periodic action allows for high throughput detection while managing energy consumption by activating optical traps only when needed rather than maintaining continuous trapping fields.
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 enhances the capture rate and sensitivity of nanopore detection, allowing for reliable analysis of biomarkers at clinically relevant concentrations, improving detection efficiency by up to six orders of magnitude compared to bulk solution methods.
Implementation Method 1
electrical detection of single analytes using nanopores in which modulations of ionic current across a nanoscale opening are used to detect particles passing through the pore
Implementation Method 2
The beads are then delivered and optically trapped in an area that is within the capture radius of the nanopore
Implementation Method 3
electrophoretic capture and detection of the target molecules can be achieved
Data Source
AI summary
A disclosed system uses modulations of ionic current across a nanopore in a membrane to detect target molecules passing through the nanopore. This principle has been applied mainly to nucleic acid sequencing, but can also be used to detect other molecular targets such as proteins and small molecules. In addition, the system delivers target molecules to a nanopore to provide label-free single molecule analysis using a chip-based system. Target molecules are concentrated on microscale carrier beads, and the beads are delivered and optically trapped in an area within the capture radius of the nanopore. The target molecules are released from the beads and detected using nanopore current modulation. In addition, the disclosed system combines sample preparation (e.g. purification, extraction, and pre-concentration) with nanopore-based readout on a microfluidic chip. Finally, target molecules can be specifically bound to carrier beads and particles are positioned within the capture volume of a nanopore using a chip-based microfluidic platform proven to handle specific detection of molecular targets from milliliters of raw sample.