Microfluidic chip for analysis of cell motility and methods for using same
Inventors
Konstantopoulos, Konstantinos • Paul, Colin Dowlin • Quinones-Hinojosa, Alfredo • Kontrogianni-Konstantopoulos, Aikaterini
Assignees
Johns Hopkins University • University of Maryland Baltimore
Publication Number
US-12201977-B2
Publication Date
2025-01-21
Expiration Date
2034-07-15
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Abstract
The present invention describes an integrated apparatus that enables identification of migratory cells directly from a specimen. The apparatus only requires a small number of cells to perform an assay and includes novel topographic features which can reliably differentiate between migratory and non-migratory cell populations in a sample. Both the spontaneous and chemotactic migration of cancer cells may be measured to distinguish between subpopulations within a tumor sample. The migratory cells identified using the apparatus and methods of the present invention may be separated and further analyzed to distinguish factors promoting metastasis within the population. Cells in the apparatus can be treated with chemotherapeutic or other agents to determine drug strategies to most strongly inhibit migration. The use of optically transparent materials in some embodiments allows a wide range of imaging techniques to be used for in situ imaging of migratory and non migratory cells in the apparatus. The apparatus and methods of the present invention are useful for predicting the metastatic propensity of tumor cells and selecting optimal drugs for personalized therapies.
Core Innovation
The invention provides an integrated apparatus, in the form of a microfluidic chip, designed for the direct identification of migratory cells from a specimen. This chip consists of at least a fluid layer with first and second channels that are adjacent and connected via a plurality of migration channels with bifurcated outlets of differing widths. These novel topographic features enable reliable differentiation between migratory and non-migratory cell populations within a small input sample.
The apparatus allows for both spontaneous and chemotactic migration analysis, making it possible to distinguish subpopulations in, for example, tumor samples. Migratory cells can be isolated and further analyzed to study factors promoting metastasis. Additionally, the chip's use of optically transparent materials supports a range of imaging techniques for in situ observation of migratory processes.
The problem addressed by the invention is the lack of a low cost, high-throughput, and easy-to-operate means for determining the motility of a cell or subpopulation of cells within a sample. Current methods require expansion of human cancers in immunodeficient mice before drug screenings can be performed, making personalized anti-metastatic medical plans difficult to develop. The invention overcomes these limitations by enabling direct and efficient evaluation and separation of migratory subpopulations for further use in therapy selection and prognosis.
Claims Coverage
The independent claim provides one main inventive feature in the apparatus design related to the configuration of channels and migration pathways enabling analysis of cellular motility.
Integrated microfluidic chip with bifurcating migration channels of different widths
The apparatus comprises a chip featuring a fluid layer with at least a first and second channel, each with its respective inlets and outlets connected to reservoirs. The first and second channels are in fluid communication via at least one migration channel, each migration channel featuring: - A single inlet end communicating with the second channel. - First and second outlet ends communicating with the first channel. - A first body portion extending from inlet to bifurcation. - First and second branch portions, which extend from the body portion to the respective outlet ends. The branch portions are connected at a bifurcation, and the first and second branch portions have different widths. The dimension of the migration channels is smaller than the main channels, and these unique topographic features are designed to restrict passage and enable the identification and differentiation of migratory cells.
The claim coverage centers around a microfluidic apparatus specifically structured with bifurcated migration channels of distinct widths, providing a mechanism for identifying and analyzing migratory cell populations based on their physical behavior within the device.
Stated Advantages
Enables reliable differentiation between migratory and non-migratory cell populations in a sample using novel topographic features.
Requires only a small number of cells to perform an assay, allowing testing from limited material.
Allows direct identification, separation, and further analysis of migratory subpopulations from a specimen.
Permits measurement of both spontaneous and chemotactic migration to distinguish subpopulations within a tumor sample.
Cells in the apparatus can be treated with agents to determine effective drug strategies for inhibiting migration.
Supports a wide range of in situ imaging techniques due to use of optically transparent materials.
Provides a low cost, high-throughput, and easy to operate means for determining cell motility that addresses gaps in current technology.
Usefulness for predicting the metastatic propensity of tumor cells and selecting optimal drugs for personalized therapies.
Documented Applications
Predicting the metastatic propensity of tumor cells for prognosis or therapy selection.
Identifying and separating migratory cell subpopulations from tumor or other biological samples for further genomic, proteomic, or molecular analysis.
Screening and selecting biologically active molecules or drugs that modulate or inhibit cell migration to inform personalized and optimal treatment regimens.
Diagnosing and treating disease or conditions in a subject by evaluating cell migration directly from patient-derived samples.
Assessing the effect of chemotherapeutic or other agents on migratory behavior of cells to determine strategies that most strongly inhibit migration.
Isolating migratory cells from a chip for transplantation into animal models for research on metastasis and cancer stem cell properties.
Using varied imaging modalities (phase contrast, fluorescence, lens-free holography, etc.) for observation of cell migration in situ in the device.
Monitoring disease progression or therapeutic efficacy by tracking cell motility in response to treatment.
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