Aptamer Microfluidics for Tumor Subtype Classification
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Solution Overview
Problem
Current methods for characterizing and treating tumors are hindered by the complexity of tumor cell populations, limited sample volumes, and the time-consuming process of sequencing and identifying tumor subtypes, which limits the effectiveness of chemotherapy and treatment planning.
Innovation Solution
A method using aptamer families and microfluidic systems, where a plurality of aptamer families are flowed over tumor cells to determine binding affinity, allowing for the classification and characterization of unknown tumor subtypes, and subsequent identification and treatment protocol development.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If nucleic acid aptamers are used to bind protein receptors on tumor cells, then specificity and sensitivity are improved, but the information content for determining cell identity is insufficient
Solution Approach 1:
The system segments the aptamer library into multiple families, each family targeting specific tumor subtypes. By dividing the comprehensive screening into family-level assessments, the system recovers information about which aptamer families bind to which tumor subtypes, overcoming the low information content of individual aptamers while maintaining high binding specificity.
Solution Approach 2:
The microfluidic device serves as an intermediary that captures and quantifies binding events between aptamer families and tumor cells. This intermediary system enables the measurement of binding affinity data that would otherwise be difficult to obtain, translating the molecular binding events into quantifiable information about tumor subtype characteristics.
2Loss of information
If traditional sequencing methods are used to characterize tumor subtypes, then comprehensive genetic information is obtained, but the time required for treatment planning is excessive
Solution Approach 1:
The system performs preliminary classification of tumor subtypes using aptamer family binding profiles before committing to comprehensive sequencing. This preliminary action provides enough information to guide treatment decisions in urgent cases, reducing the time loss while maintaining the option to perform full sequencing if needed for complex cases.
Solution Approach 2:
The system uses partial sequencing or targeted sequencing of specific genes of interest rather than full genome sequencing. This partial action provides sufficient genetic characterization for treatment planning in many cases, significantly reducing the time required while maintaining adequate information for clinical decision-making.
3Object-affected harmful factors
If minimally invasive approaches are used to harvest circulating tumor cells, then patient morbidity is reduced, but the sample volume available for analysis is limited
Solution Approach 1:
The system changes the detection parameters by using highly sensitive aptamer binding assays that can detect and characterize tumor cells at very low concentrations. This parameter change allows adequate analysis with minimal sample volumes, maintaining low patient morbidity while providing sufficient data for tumor subtype characterization.
Solution Approach 2:
The system replaces mechanical separation and manual analysis methods with microfluidic-based automated analysis. This substitution enables efficient processing of limited sample volumes, extracting maximum information from minimal cell numbers while maintaining the benefits of minimally invasive sampling.
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 accurate characterization of tumor subtypes, informs treatment protocols, and facilitates targeted therapy by leveraging the high specificity and sensitivity of aptamers, reducing treatment time and improving response to chemotherapy.
Implementation Method 1
Using nucleic acid aptamers to bind protein receptors displayed on the surface of tumor cells enjoys the advantages of having high specificity, high sensitivity
Data Source
AI summary
Methods described herein include receiving data from flowing a plurality of aptamers over a sample of tumor cells randomly affixed to a surface of a microfluidic device. The tumor cells may include one or more unknown tumor subtypes of cells. The plurality of aptamers may include a plurality of aptamer families. Each aptamer family of the plurality of aptamer families may be determined to bind to at least one possible subtype of the tumor cells. The data may include a measure of binding affinity of each aptamer family to the tumor cells. The method may include analyzing the measure of the binding affinity of each aptamer family to the tumor cells. The analyzing may include classifying the binding affinity. The method may also include determining one or more aptamer families that characterize the one or more unknown tumor subtypes of cells based on the classifying.