Abstract
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.
Highlights
Current paradigms for testing drug efficacy and toxicity are time-consuming, ineffective, and expensive.[1]
We have developed a reusable label-free microfluidics EC biosensor and integrated this system with a human organoids system
The objective was to design a system for on-line and long-term detection of cell-secreted biomarkers
Summary
Current paradigms for testing drug efficacy and toxicity are time-consuming, ineffective, and expensive.[1]. Microfluidic EC immunosensors equipped with built-in surface regeneration capacity can enable continual measurements of secreted biomarkers from organoid platforms and allow for reliable long-term evaluations upon drug and chemical exposures They could have a great impact to the field since monitoring the metabolic state of cells can be a highly dynamic process. The changes in the biomarker levels detected by the EC biosensors were compared with cellular viability and ELISA analyses to validate the accuracy of our sensing platform We believe that this robust microfluidic EC immunobiosensor system is capable of automated and continual detection of soluble biomarkers through repeated regeneration cycles within the physiological range down to nanomolar,[23] has not been reported to date. Our platform with carefully optimized functionalization, detection, and regeneration protocols will likely find widespread applications in cases where high-sensitivity, streamlined detection of biochemical species is required, such as clinical diagnostics, point-of-care diagnosis, single cell monitoring, in addition to screening of drug toxicity, efficacy, and pharmacokinetics in organ-on-a-chip systems
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