Biological Analysis System with Angled Substrate for Digital PCR
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Solution Overview
Problem
Current systems for analyzing biological samples, particularly in high-density formats like digital PCR, face challenges in providing reliable data due to the need for smaller sample volumes and efficient distribution of initial samples into numerous reaction sites, which can lead to miscalculations or missed targets.
Innovation Solution
The system employs a sample holder with a high-density array of through-holes for containing biological samples, coupled with an optical reader and thermal controller, allowing for efficient distribution and analysis of small sample volumes, and includes features like hydrophilic coatings and sealing fluids to prevent cross-contamination and evaporation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high-density sample formats are used to increase the number of reactions per test, then productivity is improved, but manufacturing precision deteriorates due to smaller sample volumes leading to unreliable data
Solution Approach 1:
The system divides the sample distribution process into multiple controlled stages: initial sample loading into a reservoir, automated dispensing into individual reaction sites, and sequential processing. This segmentation ensures each small-volume reaction receives the precise amount needed while maintaining overall high-throughput capability
Solution Approach 2:
The patent replaces manual or simple mechanical sample distribution with an automated liquid handling system that uses controlled dispensing mechanisms. This substitution ensures precise delivery of small sample volumes to each reaction site, eliminating variability and improving data reliability while maintaining high productivity
2Device complexity
If smaller sample volumes are used to accommodate high-density formats, then device complexity is reduced, but reliability deteriorates due to miscalculations and missed targets
Solution Approach 1:
The system incorporates real-time monitoring and verification of sample distribution, tracking whether targets are successfully delivered to each reaction site. This feedback mechanism allows immediate detection and correction of distribution errors, ensuring reliable target detection even with small sample volumes
Solution Approach 2:
The system performs preliminary verification steps before final reaction initiation, including checking sample presence, volume accuracy, and target delivery confirmation. This preliminary action prevents miscalculations and ensures reliability is maintained in high-density formats
3Loss of time
If automated sample distribution is implemented to improve productivity, then loss of time is reduced, but device complexity increases
Solution Approach 1:
The automated liquid handling system is designed with multi-functionality, serving both sample distribution and sample delivery verification functions. This universal design reduces the need for separate dedicated components, limiting the increase in device complexity while achieving rapid sample processing
Solution Approach 2:
The system merges the sample distribution mechanism with the reaction site preparation and verification processes into an integrated workflow. This consolidation eliminates intermediate steps and reduces overall system complexity while maintaining high-speed automated operation
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 enables reliable detection and analysis of rare alleles or target nucleotide sequences by ensuring all sample content is accurately distributed and maintained within reaction sites, reducing the risk of miscalculations and contamination, and providing efficient data collection across a large number of samples.
Implementation Method 1
an optical excitation beam may be used in real-time PCR (qPCR) reactions to illuminate hybridization probes or molecular beacons to provide fluorescent signals
Implementation Method 2
Each through-hole may be coated with a hydrophilic coating
Data Source
AI summary
A system for processing a plurality of biological samples contains a support and a temperature controller. The suppose is configured to hold a case that includes an inner chamber and a substrate located within the inner chamber, the substrate containing a plurality of isolated reaction sites containing one or more biological samples. The temperature controller is configured to maintain or control a temperature of at least one of the support, the case, or the one or more biological samples during an assay or reaction on the one or more biological samples. The support is also configured to maintain at least one of the surfaces of substrate at a positive angle relative to a horizontal plane during the assay or reaction.