Buffer Solutions for Particle Size Reduction in Sequencing
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Solution Overview
Problem
Current biological sample processing methods, particularly in nucleic acid sequencing, face challenges with particle aggregation that reduce sequencing quality and efficiency due to the large size of particles, leading to overlapping signals and decreased resolution during imaging.
Innovation Solution
The method involves processing substrates with individually addressable locations by adding a buffer solution, such as polyethylene glycol (PEG) or spermine, to decrease the average size of particles, thereby improving imaging resolution and reducing particle aggregation, allowing for higher substrate loading efficiency and better detection of nucleic acid sequences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If particles are used for nucleic acid sequencing, then sequencing capacity is increased, but particle aggregation occurs reducing sequencing quality
Solution Approach 1:
The patent applies parameter changes by modifying the physical state of particles through buffer solution treatment. Specifically, particles are subjected to changes in osmotic pressure, ionic strength, or chemical environment that cause them to shrink or change conformation, thereby reducing aggregation while maintaining sequencing capacity. This resolves the contradiction by changing particle parameters to simultaneously achieve high quantity and high reliability.
2Measurement precision
If particle size is increased for better signal detection, then detection sensitivity is improved, but signal overlap increases reducing resolution
Solution Approach 1:
The patent applies dynamics by making particle size adjustable rather than fixed. Particles can dynamically change their size in response to environmental conditions such as buffer composition, allowing them to be large during detection phases for sensitivity and small during imaging phases for resolution. This dynamic adaptability resolves the contradiction between detection sensitivity and spatial resolution.
3Productivity
If more particles are loaded onto substrate, then throughput is increased, but particle density increases causing aggregation
Solution Approach 1:
The patent applies parameter changes by modifying particle properties through buffer treatment to reduce aggregation tendency. This allows higher particle densities to be loaded onto substrates without compromising distribution uniformity, thereby increasing throughput while maintaining reliability.
4Reliability
If particle size is decreased to reduce aggregation, then sequencing quality is improved, but signal intensity decreases
Solution Approach 1:
The patent applies dynamics by enabling particles to change size based on operational requirements. Particles can be small during sequencing to reduce aggregation and improve quality, then enlarged or concentrated during detection to restore signal intensity. This temporal separation of size requirements resolves the contradiction between sequencing quality and signal intensity.
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 enhances the resolution of individual particle imaging and sequencing by reducing particle size, improving the detection of nucleic acid sequences, and increasing the number of particles that can be loaded onto a substrate, thus improving the overall sequencing quality and efficiency.
Implementation Method 1
adding a buffer solution to the substrate, wherein the buffer solution decreases an average size of at least a subset of the plurality of particles
Implementation Method 2
adding a buffer solution comprising polyethylene glycol (PEG) to the substrate, wherein the buffer solution decreases an average size of at least a subset of the plurality of particles
Data Source
AI summary
Disclosed herein are buffer solutions for decreasing the size of particles during imaging. The buffer solutions may comprise polymers, ions, or a combination thereof. The buffer solutions may decrease the sizes of particles to facilitate the resolution of individual particles during imaging. Also provided herein are methods and systems of using the same.