pH-Sensitive Dye Detection for Circulating Tumor Cell Isolation
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Solution Overview
Problem
The isolation of circulating tumor cells (CTCs) and circulating fetal cells (CFCs) from biological fluids is challenging due to their low concentration in blood, making existing methods inefficient for detection and analysis.
Innovation Solution
A method involving the use of pH-sensitive dyes that change color or emit signals when internalized by cells, allowing for detection and sorting using cell cytometers or sorters, which differentiate CTCs and CFCs based on intracellular pH differences from other cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional cell isolation methods are used, then all cells in the biological fluid can be processed, but the low concentration of target cells (CTCs/CFCs) makes detection and isolation inefficient
Solution Approach 1:
The patent applies local quality by making the detection method specific to target cells through pH-sensitive staining. The target cells (CTCs/CFCs) are selectively identified by their distinct intracellular pH characteristics, allowing differentiation from the vast majority of non-target cells in the biological fluid. This selective identification improves detection efficiency despite the low concentration of target cells.
Solution Approach 2:
The patent employs color changes as a key detection mechanism. pH-sensitive dyes are used that change color or fluorescence intensity based on the intracellular pH of target cells. This visual and optical signal change enables rapid identification and sorting of target cells from the background population, significantly improving detection efficiency without requiring concentration enrichment.
2Speed
If pH-sensitive dyes are used for rapid detection, then detection speed increases, but the complexity of the device and methodology increases
Solution Approach 1:
The patent uses pH-sensitive dyes as intermediary substances that mediate between the intracellular pH environment and the detection system. These dyes convert the biochemical property (pH) into an optical signal that can be detected by flow cytometers or other standard equipment. This intermediary approach enables rapid detection while utilizing existing instrumentation, thereby limiting the increase in device complexity.
Solution Approach 2:
The patent replaces complex mechanical cell separation methods with a chemical-optical detection approach. Instead of using mechanical means to isolate and identify cells, the system uses pH-sensitive fluorescent dyes and optical detection to rapidly identify target cells based on their pH characteristics. This substitution significantly increases detection speed while the complexity increase is limited to chemical reagents and optical detection capabilities.
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
Enables rapid and efficient identification, counting, and isolation of CTCs and CFCs, facilitating genetic and medical analyses, including early cancer detection, monitoring disease progression, and prenatal screening.
Implementation Method 1
A method involving the use of pH-sensitive dyes that change color or emit signals when internalized by cells, allowing for detection and sorting using cell cytometers or sorters, which differentiate CTCs and CFCs based on intracellular pH differences from other cells.
Data Source
AI summary
The present invention generally relates to devices and methods for determining and/or isolating cells. One aspect is generally directed to methods and devices for detecting, identifying, counting, and/or potentially sorting cells of interest in blood or other biological sample. In some embodiments, blood samples (or other biological fluids) may be treated with signaling entities, such as pH-sensitive entities, that change color or otherwise produce a signal in suitable internal environments. For example, certain cells, such as cancer or fetal cells, may have differences in intracellular pH compared to other cells, which can be detected using pH-sensitive entities. In certain embodiments, the cells may be sorted based on such signaling entities; for example, illumination of cells in a suitable machine for sorting cells (e.g., using fluorescent light) may allow determination of the cells, which may also be recovered or isolated for further manipulation in some cases.