Microcavity array (MCA)-based biosensor chip for functional drug screening of 3D tissue models

Kloß, Daniel; Kurz, Randy; Jahnke, Heinz‐Georg; Fischer, M.; Rothermel, Andrée; Anderegg, Ulf; Simon, Jan C.

doi:10.1016/j.bios.2008.01.003

Cited by 73 publications

(39 citation statements)

References 18 publications

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“…These impedance techniques have been applied to a wide range of biological studies, including cell attachment (Choi et al 2007), cell adhesion and spreading (Lo et al 1995;Luong et al 2001;Wegener et al 2000), metastasis (Keese et al 2002), cell transformation (Park et al 2009), apoptosis (Arndt et al 2004), and drug-induced cellular activities (Xiao et al 2002;Xiao and Luong 2003;Klo et al 2008;Linderholm et al 2007). In addition, impedance techniques have been used to investigate cellular parameters related to cell-cell and cell-substrate junction formation Keese 1991, 1993;Lo et al 1999;Burns et al 2000;Kataoka et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Interdigitated microelectrode-based microchip for electrical impedance spectroscopic study of oral cancer cells

Mamouni

Yang

2011

Biomed Microdevices

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In this study, electric/electrochemical impedance spectroscopy and cyclic voltammetry were used to study the cellular activities of oral cancer cell line CAL 27, including the kinetics of cell adhesion, spreading, and cell proliferation on interdigitated microelectrodes (IMEs). Impedance spectra of CAL 27 cells on IMEs electrodes were obtained in cell growth medium and in 0.1 M PBS with 50 mM [Fe(CN)₆]³⁻/⁴⁻ as redox probe. Equivalent circuits were used to model both cases. In cell growth medium, impedance spectra allowed us to analyze the changes in capacitance and resistance due to cell attachment on the IMEs over the entire experiment period. It was found that cell spreading caused the most significant decrease in capacitance component and slight increase in resistance component. Impedance change at given frequencies (between 10 kHz to 100 kHz) was found to be linearly increased with increasing cell number of CAL 27 on the IMEs. In comparison with non-cancer oral epithelial cells (Het-1A), at equal cell number, cancer cells always generated impedance several folds higher than that of non-cancer cells. In the presence of [Fe(CN)₆]³⁻/⁴⁻, impedance spectra allowed us to analyze the change in electron transfer resistance of IMEs due to cell attachment, in which an increase trend was observed at 24 h with increasing cell number from 2500 cells to 10,000 cells on IMEs. Double layer capacitance was also affected by cell attachment, and a decrease in double layer capacitance was observed with increasing cell number on the electrodes. Cyclic voltammetric measurements correlated well with the impedance results. The results of this study demonstrated the use of electrochemical approaches to obtain and understand cellular behaviors/activities of oral cancer cells, potentially providing useful tools for cancer cell research.

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Section: Introductionmentioning

confidence: 99%

Interdigitated microelectrode-based microchip for electrical impedance spectroscopic study of oral cancer cells

Mamouni

Yang

2011

Biomed Microdevices

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“…This novel microcavity-multi-electrode array can be translated and transferred in a concept for multi-well-microarrays resulting in a device for high content and high throughput screening in chemical and pharmaceutical industry. The microarray can be coupled with various 3D tissues or biopsy materials for a noninvasive, labelling-free, and continuous screening and/or diagnosis of cellular alterations under real-time conditions (33)(34)(35). Thereby, an automated high-content and/or high throughput screening of biologic active compounds on three-dimensional tissues derived from biopsies of tumour, already established cell lines, or primary cell cultures can be achieved.…”

Section: Nanotechnology Development and Applicationmentioning

confidence: 99%

“…Demonstration of bioimpedance as physiological marker of cell physiology as well as introduction of multielectrode array technology surely will facilitate the development of cytomics by provision of the new physical parameters on the individual cell (32,34). In the laboratory course, participants could visit the Division of Molecular Processing Technology of the BBZ where these applications were presented.…”

Section: Nanotechnology Development and Applicationmentioning

confidence: 99%

Cytomics and nanobioengineering

Pierzchalski¹,

Robitzki²,

Mittag³

et al. 2008

Cytometry Part B Clinical

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The finding that an individual's genome differs as much as by many million variants from that of the human reference assembly diminished the great enthusiasm that every disease could be predicted based on nucleotide polymorphisms. Even individual cells of an organ may be specifically equipped to perform specific tasks and that the information of individual cells in a cell system is key information to understand function or dysfunction. Therefore, cytomics received great attention during the last years as it allows to quantitatively and qualitatively analyzing great number of individual cells, cell constituents, and of their intracellular and functional interactions in a cellular system and also giving the concept of analysis of these data.Exhaustive data extraction from multiparametric assays and multiple tests are the prerequisite for prediction of drug toxicity. Cytomics, as novel approach for unsupervised data analysis give a chance to find the most predictive parameters, which describe best the toxicity of a chemical. Cytomics is intrinsically connected to drug development and drug discovery.Focused on small structures, nanobioengineering is the ideal partner of cytomics, the systems biological discipline for cell population analysis. Realizing the idea ''from the molecule to the patient'' develops and offers chemical compounds, proteins, and other biomolecules, cells as well as tissues as instruments and products for a wide variety of biotechnological and biomedical applications.The integrative nanobioengineering combining different disciplines of nanotechnology will promote the development of innovative therapies and diagnostic methods. It can improve the precision of the measurements with focus on single cell analysis. By nanobioengineering and whole body imaging techniques, cytomics covers the field from molecules through bacterial cells, eukaryotic tissues, and organs to small animal live analysis. Toxicological testing and medical drug development are currently strongly broadening. It harbors the promise to substantially impact on various fields of biomedicine, drug discovery, and predictive medicine.As the number of scientific data is rising exponentially, new data analysis tools and strategies like cytomics and nanobioengineering take a lead and get closer to application. Bionanoengineering may strongly support the quantitative data supply, thus strengthening the rationale for cytomics approach. q

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“…Accurate monitoring of biological functions of cells (e.g., levels of cell‐secreted biomarkers, enzyme, etc. )6 requires detection and analysis of trace amounts of biomarkers of interest over an extended period of time 7. For example, many drugs or toxic compounds may result in chronic cellular reactions or delayed cell responses and lead to gradually changing secretion of biomarkers typically at low abundance.…”

Section: Introductionmentioning

confidence: 99%

Label‐Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes

et al. 2017

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Development of an efficient sensing platform capable of continual monitoring of biomarkers is needed to assess the functionality of the in vitro organoids and to evaluate their biological responses toward pharmaceutical compounds or chemical species over extended periods of time. Here, a novel label‐free microfluidic electrochemical (EC) biosensor with a unique built‐in on‐chip regeneration capability for continual measurement of cell‐secreted soluble biomarkers from an organoid culture in a fully automated manner without attenuating the sensor sensitivity is reported. The microfluidic EC biosensors are integrated with a human liver‐on‐a‐chip platform for continual monitoring of the metabolic activity of the organoids by measuring the levels of secreted biomarkers for up to 7 d, where the metabolic activity of the organoids is altered by a systemically applied drug. The variations in the biomarker levels are successfully measured by the microfluidic regenerative EC biosensors and agree well with cellular viability and enzyme‐linked immunosorbent assay analyses, validating the accuracy of the unique sensing platform. It is believed that this versatile and robust microfluidic EC biosensor that is capable of automated and continual detection of soluble biomarkers will find widespread use for long‐term monitoring of human organoids during drug toxicity studies or efficacy assessments of in vitro platforms.

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Microcavity array (MCA)-based biosensor chip for functional drug screening of 3D tissue models

Cited by 73 publications

References 18 publications

Interdigitated microelectrode-based microchip for electrical impedance spectroscopic study of oral cancer cells

Interdigitated microelectrode-based microchip for electrical impedance spectroscopic study of oral cancer cells

Cytomics and nanobioengineering

Label‐Free and Regenerative Electrochemical Microfluidic Biosensors for Continual Monitoring of Cell Secretomes

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