Multiplex Assay for Signal Transducer Activation in Circulating Tumor Cells
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Solution Overview
Problem
Current methods for detecting the activation states of signal transducers in circulating cells of solid tumors are not specific or sensitive enough for diagnostic and prognostic purposes, particularly in the context of heterogeneous tumors and metastatic cancers, where biopsy samples may not represent the tumor population accurately.
Innovation Solution
A multiplex, high-throughput assay method involving specific binding partners that form complexes with signal transducers, where one set binds independently of activation state and another set binds dependent on activation state, labeled with distinct moieties to indicate activation states, utilizing a solid support for immobilization and detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional detection methods are used for signal transducers in circulating cells, then the detection process is simpler, but the measurement precision and sensitivity are insufficient for diagnostic and prognostic purposes
Solution Approach 1:
The assay is segmented into distinct functional modules: signal transducer extraction from circulating cells, affinity binding partners for specific recognition, solid support array for organized presentation, and detection systems for signal transduction. Each module performs a specific function, allowing high precision through specialized components while managing overall complexity through modular organization.
Solution Approach 2:
The invention transitions from conventional two-dimensional detection to a three-dimensional organized array system on solid support. Signal transducers are presented in a structured spatial arrangement that enables multiplexed detection of multiple transducers simultaneously, increasing measurement precision without proportionally increasing operational complexity.
2Reliability
If biopsy is performed on primary tumors to analyze tumor samples, then molecular analysis can be obtained, but the sample may not represent the heterogeneity of the tumor population and metastatic tumors cannot be biopsied
Solution Approach 1:
The invention extracts and analyzes circulating tumor cells directly from blood samples, taking out the need for invasive biopsy procedures. This extraction approach provides direct access to metastatic tumor cells in their natural circulation environment, ensuring sample representativeness of the actual tumor population while greatly improving ease of operation through minimally invasive blood draws.
Solution Approach 2:
Circulating tumor cells serve as an intermediary between the primary tumor and the detection system. These cells carry molecular information from the tumor population and can be accessed through blood draws, acting as a mediator that provides reliable tumor representation without requiring direct biopsy of the tumor mass itself.
3Measurement precision
If multiplex, high-throughput assay methods are implemented for detecting signal transducer activation states, then diagnostic and prognostic accuracy is improved, but the device complexity and assay procedure become more complex
Solution Approach 1:
The solid support array system provides universal functionality for detecting multiple signal transducers simultaneously. The same basic array structure and detection methodology can be applied to detect various different signal transducers by simply changing the affinity binding partners, enabling multiplexed high-throughput detection without requiring separate complex systems for each transducer.
Solution Approach 2:
The invention uses parameter changes in the form of different affinity binding partners with specific binding characteristics for each signal transducer. By varying the binding affinity and specificity parameters of the partners while maintaining the same overall assay structure, the system achieves high detection accuracy for multiple transducers without proportionally increasing device complexity.
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 allows for precise detection of signal transducer activation states in circulating cells, facilitating cancer prognosis and personalized therapy selection by enabling sensitive and specific analysis of tumor cell populations in accessible biological fluids.
Implementation Method 1
the first binding partners restrained in an array and adapted to selectively immobilize and organize the corresponding signal transducers on the array
Implementation Method 2
the second binding partners bind the corresponding signal transducers independent of their activation state
Implementation Method 3
the third binding partners bind the corresponding signal transducers dependent of their activation state
Implementation Method 4
the first and second moieties generate first and second signals wherein the second signal is detectable and generated dependent on channeling of the first signal between the moieties
Data Source
AI summary
Methods and kits for detecting the activation states of a plurality of signal transducers of circulating cells of a solid tumor in a specific, multiplex, high-throughput assay are described. The methods comprise: contacting the signal transducers extracted from the cells with first, second, and third binding partners specific for each of the signal transducers to produce signal transducer-binding partner complexes. The second binding partners bind the corresponding signal transducers independent of their activation state and are labeled with a first moiety, and the third binding partners bind the corresponding signal transducers dependent of their activation state and are labeled with a second moiety. The first and second moieties are detected as an indication of the activation states of the plurality of signal transducers.