Self-assembled sensor-in-a-tube as a versatile tool for label-free EIS viability investigation of cervical cancer cells
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Eashika Ghosh
, Daniil Karnaushenko
and Oliver G. Schmidt
Abstract
The advancement of micro and nanotechnology has led to the manufacturing of miniaturized sensors with improved functionalities for highly sensitive point of care devices. This work is particularly focused on analysing cancer cells and the effect of a model drug on their survival rate. To that end, we developed a highly sensitive rolled-up micro-electrochemical impedance spectroscopy sensor, encapsulated into a microfluidic channel. The sensor was built by strain engineering of shapeable materials and with diameters close to the cell size to improve their sensitivity. To demonstrate the platform performance, we first carried out measurements with different electrode geometries using cell medium at different concentrations. We also performed measurements using cancer cell suspensions, obtaining distinct signals from single cells, cell clusters and cellular debris. Finally, cancer cells were treated with an anticancer drug (Camptothecin), at different concentrations, over the same period, and further analysed using the developed platform.
Funding source: German Research Foundation DFG SPP 1857 ESSENCE
Award Identifier / Grant number: KA5051/1-1 and ME4868/2-1
Acknowledgements
O.G.S. acknowledges financial support by the Leibniz Program of the German Research Foundation (SCHM 1298/26-1). M. Medina-Sánchez acknowledges financial support by the European Union's Horizon 2020 research and innovation program (Grant agreement No. 853609). The authors warmly thank F. Hebenstreit for the biological experiment’s assistance. The support of the clean room team headed by R. Engelhard and the assistance in development of the experimental setups by the research technology department of IFW Dresden is greatly appreciated. We further thank C. Krien and I. Fiering for the deposition of metallic thin films, F. Striggow for SEM analysis.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: The work was financially supported by the German Research Foundation DFG SPP 1857 ESSENCE grant (KA5051/1-1 and ME4868/2-1).
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Conflict of interest statement: The authors declare no conflict of interest.
References
[1] M. Vu, J. Yu, O. A. Awolude, and L. Chuang, “Cervical cancer worldwide,” Curr. Probl. Cancer, vol. 42, no. 5, pp. 457–465, 2018, https://doi.org/10.1016/j.currproblcancer.2018.06.003.Search in Google Scholar PubMed
[2] World Health Organization, WHO Guideline for Screening and Treatment of Cervical Pre-cancer Lesions for Cervical Cancer Prevention: Use of mRNA Tests for Human Papillomavirus (HPV). 2nd ed., 2021, [Online]. Available at: https://www.who.int/publications/i/item/9789240030824.Search in Google Scholar
[3] N. Wentzensen, M. Schiffman, T. Palmer, and M. Arbyn, “Triage of HPV positive women in cervical cancer screening,” J. Clin. Virol., vol. 76, pp. S49–S55, 2016, https://doi.org/10.1016/j.jcv.2015.11.015.Search in Google Scholar PubMed PubMed Central
[4] A. Saadatpour, S. Lai, G. Guo, and G. C. Yuan, “Single-cell analysis in cancer genomics,” Trends Genet., vol. 31, no. 10, pp. 576–586, 2015, https://doi.org/10.1016/j.tig.2015.07.003.Search in Google Scholar PubMed PubMed Central
[5] A. Z. Mirakabadi, A. Sarzaeem, S. Moradhaseli, A. Sayad, and M. Negahdary, “Necrotic effect versus apoptotic nature of Camptothecin in human cervical cancer cells,” Iran. J. Cancer Prev., vol. 5, no. 3, pp. 109–116, 2012.Search in Google Scholar
[6] J. Wu, M. Dong, C. Rigatto, Y. Liu, and F. Lin, “Lab-on-chip technology for chronic disease diagnosis,” npj Digit. Med., vol. 1, no. 1, pp. 1–11, 2018, https://doi.org/10.1038/s41746-017-0014-0.Search in Google Scholar PubMed PubMed Central
[7] B. Sharma and A. Sharma, “Microfluidics: recent advances toward lab-on-chip applications in bioanalysis,” Adv. Eng. Mater., vol. 24, no. 2100738, 2022.10.1002/adem.202100738Search in Google Scholar
[8] C. D. Ahrberg, A. Manz, and B. G. Chung, “Polymerase chain reaction in microfluidic devices,” Lab Chip, vol. 16, no. 20, pp. 3866–3884, 2016, https://doi.org/10.1039/c6lc00984k.Search in Google Scholar PubMed
[9] A. Joshi, A. Vishnu, T. Sakorikar, A. M. Kamal, J. S. Vaidya, and H. J. Pandya, “Recent advances in biosensing approaches for point-of-care breast cancer diagnostics: challenges and future prospects,” Nanoscale Adv., vol. 3, no. 19, pp. 5542–5564, 2021, https://doi.org/10.1039/d1na00453k.Search in Google Scholar PubMed PubMed Central
[10] J. Suikkola, T. Björninen, M. Mosallaei, et al., “Screen-printing fabrication and characterization of stretchable electronics,” Sci. Rep., vol. 6, no. May, pp. 1–8, 2016. https://doi.org/10.1038/srep25784.Search in Google Scholar PubMed PubMed Central
[11] J. Izdebska, “Printing on polymers: fundamentals and applications print.” Polym. Fundam. Appl., no. July, 2015, pp. 1–424.Search in Google Scholar
[12] V. Narayanamurthy, Z. E. Jeroish, K. S. Bhuvaneshwari, et al., “Advances in passively driven microfluidics and lab-on-chip devices: a comprehensive literature review and patent analysis,” RSC Adv., vol. 10, no. 20, pp. 11652–11680, 2020. https://doi.org/10.1039/d0ra00263a.Search in Google Scholar PubMed PubMed Central
[13] G. Dutta, J. Rainbow, U. Zupancic, S. Papamatthaiou, P. Estrela, and D. Moschou, “Microfluidic devices for label-free DNA detection,” Chemosensors, vol. 6, no. 4, 2018, https://doi.org/10.3390/chemosensors6040043.Search in Google Scholar
[14] Q. Hassan, S. Ahmadi, and K. Kerman, “Recent advances in monitoring cell behavior using cell-based impedance spectroscopy,” Micromachines, vol. 11, no. 6, 2020, https://doi.org/10.3390/MI11060590.Search in Google Scholar
[15] L. L. Crowell, J. S. Yakisich, B. Aufderheide, and T. N. G. Adams, “Electrical impedance spectroscopy for monitoring chemoresistance of cancer cells,” Micromachines, vol. 11, no. 9, 2020, https://doi.org/10.3390/mi11090832.Search in Google Scholar PubMed PubMed Central
[16] Y. Feng, L. Huang, P. Zhao, F. Liang, and W. Wang, “A microfluidic device integrating impedance flow cytometry and electric impedance spectroscopy for high-efficiency single-cell electrical property measurement,” Anal. Chem., vol. 91, no. 23, pp. 15204–15212, 2019, https://doi.org/10.1021/acs.analchem.9b04083.Search in Google Scholar PubMed
[17] A. Sun, A. G. Venkatesh, and D. A. Hall, “A multi-technique reconfigurable electrochemical biosensor: enabling personal health monitoring in mobile devices,” IEEE Trans. Biomed. Circuits Syst., vol. 10, no. 5, pp. 945–954, 2016, https://doi.org/10.1109/TBCAS.2016.2586504.Search in Google Scholar PubMed
[18] J. Cottet, A. Kehren, H. van Lintel, F. Buret, M. Frénéa-Robin, and P. Renaud, “How to improve the sensitivity of coplanar electrodes and micro channel design in electrical impedance flow cytometry: a study,” Microfluid. Nanofluidics, vol. 23, no. 1, 2019, https://doi.org/10.1007/s10404-018-2178-6.Search in Google Scholar
[19] L. Wang, L. A. Flanagan, N. L. Jeon, E. Monuki, and A. P. Lee, “Dielectrophoresis switching with vertical sidewall electrodes for microfluidic flow cytometry,” Lab Chip, vol. 7, no. 9, pp. 1114–1120, 2007, https://doi.org/10.1039/b705386j.Search in Google Scholar PubMed PubMed Central
[20] S. Choi and J. K. Park, “Microfluidic system for dielectrophoretic separation based on a trapezoidal electrode array,” Lab Chip, vol. 5, no. 10, pp. 1161–1167, 2005, https://doi.org/10.1039/b505088j.Search in Google Scholar PubMed
[21] Y. Yu, J. Chen, and J. Zhou, “Parallel plate lab on a chip based on digital microuidics for on-chip electrochemical analysis,” J. Micromech. Microeng., vol. 24, no. 1, 2014, https://doi.org/10.1088/0960-1317/24/1/015020.Search in Google Scholar
[22] G. Kang, S. K. Yoo, H. I. Kim, and J. H. Lee, “Differentiation between normal and cancerous cells at the single cell level using 3-D electrode electrical impedance spectroscopy,” IEEE Sensor. J., vol. 12, no. 5, pp. 1084–1089, 2012, https://doi.org/10.1109/JSEN.2011.2167227.Search in Google Scholar
[23] M. Ibrahim, J. Claudel, D. Kourtiche, and M. Nadi, “Geometric parameters optimization of planar interdigitated electrodes for bioimpedance spectroscopy,” J. Electr. Bioimpedance, vol. 4, no. 1, pp. 13–22, 2013, https://doi.org/10.5617/jeb.304.Search in Google Scholar
[24] S. M. Weiz, M. Medina-Sánchez, and O. G. Schmidt, “Advanced biosystems – microsystems for single-cell analysis.pdf,” Adv. Biosys.,vol. 2, no. 1700193, 2018.10.1002/adbi.201700193Search in Google Scholar
[25] E. J. Smith, W. Xi, D. Makarov, et al., “Lab-in-a-tube: ultracompact components for on-chip capture and detection of individual micro-/nanoorganisms,” Lab Chip, vol. 12, no. 11, pp. 1917–1931, 2012. https://doi.org/10.1039/c2lc21175k.Search in Google Scholar PubMed
[26] C. S. Martinez-Cisneros, S. Sanchez, W. Xi, and O. G. Schmidt, “Ultracompact three-dimensional tubular conductivity microsensors for ionic and biosensing applications,” Nano Lett., vol. 14, no. 4, pp. 2219–2224, 2014, https://doi.org/10.1021/nl500795k.Search in Google Scholar PubMed PubMed Central
[27] M. Medina-Sánchez, B. Ibarlucea, N. Pérez, et al., “High-performance three-dimensional tubular nanomembrane sensor for DNA detection,” Nano Lett., vol. 16, no. 7, pp. 4288–4296, 2016. https://doi.org/10.1021/acs.nanolett.6b01337.Search in Google Scholar PubMed
[28] C. S. Bausch, C. Heyn, W. Hansen, et al., “Ultra-fast cell counters based on microtubular waveguides,” Sci. Rep., vol. 7, pp. 1–11, 2017. https://doi.org/10.1038/srep41584.Search in Google Scholar PubMed PubMed Central
[29] A. I. Egunov, Z. Dou, D. D. Karnaushenko, et al.., “Impedimetric microfluidic sensor-in-a-tube for label-free immune cell Analysis,” Small, vol. 17, no. 2002549, 2021.10.1002/smll.202002549Search in Google Scholar PubMed
[30] J. C. Mijn, K. W. Eng, P. Chandra, et al., “The genomic landscape of metastatic clear cell renal cell carcinoma after systemic therapy,” Mol. Oncol., vol. 16, pp. 2348–2395, 2022. https://doi.org/10.1002/1878-0261.13204.Search in Google Scholar PubMed PubMed Central
[31] A. Susloparova, D. Koppenhöfer, X. T. Vu, M. Weil, and S. Ingebrandt, “Impedance spectroscopy with field-effect transistor arrays for the analysis of anti-cancer drug action on individual cells,” Biosens. Bioelectron., vol. 40, no. 1, pp. 50–56, 2013, https://doi.org/10.1016/j.bios.2012.06.006.Search in Google Scholar PubMed
© 2022 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Editorial
- Research Articles
- Ultrasensitive marker-free biomolecular THz-detection for tumor-related analytics
- Terahertz subwavelength sensing with bio-functionalized germanium fano-resonators
- Concepts for millimeter wave-based detection of African trypanosomes in field-compatible liquid systems
- Millimeter-wave imaging and near-field spectroscopy for burn wound assessment
- A compact breath gas sensor system based on terahertz/millimeter-wave gas spectroscopy
- Evolution of a theranostic applicator for microwave ablation treatment
- Towards a fully integrated sub-THz microfluidic sensor platform for dielectric spectroscopy
- Towards single-cell pulsed EPR using VCO-based EPR-on-a-chip detectors
- Label-free single-cell counting and characterization in the GHz-range
- Self-assembled sensor-in-a-tube as a versatile tool for label-free EIS viability investigation of cervical cancer cells
Articles in the same Issue
- Frontmatter
- Editorial
- Editorial
- Research Articles
- Ultrasensitive marker-free biomolecular THz-detection for tumor-related analytics
- Terahertz subwavelength sensing with bio-functionalized germanium fano-resonators
- Concepts for millimeter wave-based detection of African trypanosomes in field-compatible liquid systems
- Millimeter-wave imaging and near-field spectroscopy for burn wound assessment
- A compact breath gas sensor system based on terahertz/millimeter-wave gas spectroscopy
- Evolution of a theranostic applicator for microwave ablation treatment
- Towards a fully integrated sub-THz microfluidic sensor platform for dielectric spectroscopy
- Towards single-cell pulsed EPR using VCO-based EPR-on-a-chip detectors
- Label-free single-cell counting and characterization in the GHz-range
- Self-assembled sensor-in-a-tube as a versatile tool for label-free EIS viability investigation of cervical cancer cells