Multiplexed Lymphocyte Testing via Error-Correcting Codes
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Solution Overview
Problem
Current methods for determining lymphocyte receptor sequences that recognize specific antigens suffer from high false positive and false negative rates, and fail to accurately identify sequences in pool-based detection formats.
Innovation Solution
A method involving sorting antigens into reaction mixtures, contacting with T cells to expand clones, separating activated cells, sequencing, and using error-correcting codes and decoding algorithms to detect specific T cell receptor chain sequences, thereby improving accuracy and reducing false positives/negatives.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If pool-based detection formats are used to determine lymphocyte receptor sequences, then throughput and efficiency are improved, but false positive and false negative rates increase
Solution Approach 1:
The patent divides the pool-based detection into multiple individual reaction mixtures, each containing a unique subset of antigens. By sorting antigens into distinct pools and analyzing individual reaction mixtures rather than a single large pool, the method maintains high throughput while improving accuracy through error-correcting codes that can identify and correct false positives and negatives.
Solution Approach 2:
The patent implements feedback mechanisms through error-correcting codes and decoding algorithms that analyze the pattern of reactions across multiple antigen pools. The system uses the collective information from multiple reactions to verify results, providing feedback that allows identification of true positive signals while filtering out false positives and negatives.
2Device complexity
If conventional sequencing methods are used to identify T cell receptor chains, then simplicity is maintained, but false positive and false negative rates remain high
Solution Approach 1:
The patent applies error-correcting codes to the antigen sorting process before sequencing occurs. By pre-organizing antigens into coded pools and tracking which antigens are present in each reaction mixture, the system establishes a framework that enables accurate sequence identification even when individual sequencing results contain errors.
Solution Approach 2:
The patent replaces conventional direct sequencing methods with a coded pool-based detection system that uses mathematical decoding algorithms. Instead of relying solely on direct sequencing accuracy, the system substitutes a computational approach that uses error-correcting codes to determine the correct T cell receptor sequences associated with specific antigens.
3Productivity
If multiple antigens are tested simultaneously in pool-based formats, then testing efficiency is improved, but the ability to accurately identify specific receptor-antigen pairs deteriorates
Solution Approach 1:
The patent creates a universal coding system that can identify multiple antigen-specific T cell receptor sequences simultaneously. Each antigen is assigned a unique code pattern across multiple pools, allowing the system to decode and identify which specific antigens correspond to which T cell receptor sequences, even when many antigens are tested in parallel.
Solution Approach 2:
The patent adds a dimensional layer to the detection system by organizing antigens into multiple pools with coded patterns rather than testing them in a single dimension. This multi-dimensional pool structure allows the system to track and identify specific receptor-antigen pairs through the pattern of reactions across different pools, preventing loss of pairing information.
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 method enhances the accuracy of identifying lymphocyte receptor sequences by reducing false positives and negatives, allowing for precise detection of antigen-specific T cell receptor chains in pool-based formats.
Implementation Method 1
providing a condition for a first activated T cell in at least one reaction mixture of the plurality of reaction mixtures to expand in number such that a plurality of T cell clones is formed
Implementation Method 2
the detecting comprises applying, using a processor, a decoding algorithm, wherein the decoding algorithm is configured to detect the unique antigen specific for the T cell receptor chain sequence
Data Source
AI summary
Described herein is a method for determining a lymphocyte cell receptor chain sequence specific to a unique antigen, comprising: sorting a plurality of antigens into a plurality of reaction mixtures, wherein the sorting comprises adding a unique antigen of the plurality of antigens to a unique subset of the plurality of reaction mixtures such that two different unique antigens are not added to the unique subset; contacting each reaction with a biological sample comprising a plurality of lymphocytes; separating a target lymphocyte from a subset of the plurality of lymphocytes, wherein the target lymphocyte recognizes the unique antigen; after separating the target lymphocyte, sequencing nucleic acids of the target lymphocyte to obtain the lymphocyte receptor chain sequence, wherein the sequencing is performed by single-cell sequencing; and detecting the unique antigen, wherein the detecting comprises: computing a frequency of lymphocyte cells that express the lymphocyte receptor chain sequence.