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Published on: July 3, 2013
Plasmonic Functional Assay Platform Determines the Therapeutic Profile of Cancer Cells
Arif E Cetin1, Seda Nur Topkaya2, Ziya Ata Yazici3
1Izmir Biomedicine and Genome Center, Balcova, 35330 Izmir, Turkey.
Abstract:
Functional assay platforms could identify the biophysical properties of cells and their therapeutic response to drug treatments. Despite their strong ability to assess cellular pathways, functional assays require large tissue samples, long-term cell culture, and bulk measurements. Even though such a drawback is still valid, these limitations did not hinder the interest in these platforms for their capacity to reveal drug susceptibility. Some of the limitations could be overcome with single-cell functional assays by identifying subpopulations using small sample volumes. Along this direction, in this article, we developed a high-throughput plasmonic functional assay platform to identify the growth profile of cells and their therapeutic profile under therapies using mass and growth rate statistics of individual cells. Our technology could determine populations' growth profiles using the growth rate data of multiple single cells of the same population. Evaluating spectral variations based on the plasmonic diffraction field intensity images in real time, we could simultaneously monitor the mass change for the cells within the field of view of a camera with the capacity of > ∼500 cells/h scanning rate. Our technology could determine the therapeutic profile of cells under cancer drugs within few hours, while the classical techniques require days to show reduction in viability due to antitumor effects. The platform could reveal the heterogeneity within the therapeutic profile of populations and determine subpopulations showing resistance to drug therapies. As a proof-of-principle demonstration, we studied the growth profile of MCF-7 cells and their therapeutic behavior to standard-of-care drugs that have antitumor effects as shown in the literature, including difluoromethylornithine (DFMO), 5-fluorouracil (5-FU), paclitaxel (PTX), and doxorubicin (Dox). We successfully demonstrated the resistant behavior of an MCF-7 variant that could survive in the presence of DFMO. More importantly, we could precisely identify synergic and antagonistic effects of drug combinations based on the order of use in cancer therapy. Rapidly assessing the therapeutic profile of cancer cells, our plasmonic functional assay platform could be used to reveal personalized drug therapies for cancer patients.
Insights
A new plasmonic functional assay platform rapidly assesses single-cell drug responses, identifying cancer cell heterogeneity and guiding personalized therapies. This high-throughput technology overcomes limitations of traditional methods for faster treatment insights.
Area of Science:
- Biophysics
- Cell Biology
- Cancer Research
Background:
- Traditional functional assays require large samples and long culture times, limiting their use for rapid drug susceptibility testing.
- Single-cell analysis offers potential to overcome bulk measurement limitations and identify cellular subpopulations.
- Existing methods struggle to provide rapid, detailed insights into individual cell responses to therapies.
Purpose of the Study:
- To develop a high-throughput plasmonic functional assay platform for real-time, single-cell analysis of cellular growth and therapeutic responses.
- To rapidly determine drug susceptibility, identify therapeutic heterogeneity, and assess drug combination effects.
- To enable personalized cancer therapy by quickly profiling individual cell responses to various treatments.
Main Methods:
- Developed a high-throughput plasmonic functional assay utilizing real-time spectral variations and plasmonic diffraction field intensity imaging.
- Monitored individual cell mass and growth rates at a scanning rate of >500 cells/h.
- Applied the platform to study MCF-7 cells' response to DFMO, 5-FU, PTX, and Dox, including drug combinations.
Main Results:
- The platform determined population growth profiles and individual cell mass changes in real time.
- Therapeutic profiles were assessed within hours, significantly faster than traditional methods requiring days.
- Identified drug-resistant subpopulations within MCF-7 cells and precisely determined synergistic/antagonistic effects of drug combinations.
Conclusions:
- The developed plasmonic functional assay platform enables rapid, high-throughput, single-cell analysis of cellular growth and drug response.
- This technology reveals cellular heterogeneity and identifies resistant subpopulations, crucial for effective cancer treatment.
- The platform facilitates personalized drug therapy by providing rapid insights into individual patient cell responses and optimal drug combinations.
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