pH-Sensitive Dye Cell Isolation via Intracellular State Change
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Solution Overview
Problem
Current methods are inefficient in isolating and detecting circulating tumor cells, fetal cells, and stem cells due to their low concentration in biological fluids, making it challenging for genetic and medical analyses.
Innovation Solution
A device and method utilizing pH-sensitive dyes that change state within target cells, allowing for their detection and isolation using cell cytometers or sorters, which differentiate them from non-target cells based on intracellular pH differences.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional cell detection methods are used, then detection capability is limited, but isolation efficiency and speed are insufficient due to low target cell concentration
Solution Approach 1:
The patent changes the chemical parameter of the dye molecule by converting it from a neutral form that cannot cross cell membranes to a charged form that can be retained inside cells. This parameter change enables specific accumulation of the dye in target cells, making them detectable and isolatable despite their low concentration in the biological fluid
Solution Approach 2:
The patent utilizes color changes of the dye molecule as it transitions between neutral and charged states, and as it accumulates in target cells. The dye exhibits different absorption and emission spectra depending on its protonation state and concentration, enabling optical detection and sorting of target cells based on their unique color signature
2Measurement precision
If pH-sensitive dyes are used to differentiate target cells, then detection precision improves, but device complexity increases
Solution Approach 1:
The patent employs the cell's own physiological properties (intracellular pH differences and membrane transport mechanisms) to perform the differentiation function. The target cells actively accumulate the dye through their own pH-regulating mechanisms, eliminating the need for external complex differentiation systems and enabling simple optical detection
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 and isolation of target cells, facilitating genetic analysis, cancer monitoring, and therapeutic applications by leveraging pH-sensitive entities that fluoresce within specific pH ranges.
Implementation Method 1
pH-sensitive dyes that change state within target cells, allowing for their detection and isolation using cell cytometers or sorters, which differentiate them from non-target cells based on intracellular pH differences
Data Source
AI summary
Some embodiments of the present invention generally relate to devices and methods for determining and/or isolating cells. For example, 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.