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      Clinical translation of microfluidic sensor devices: focus on calibration and analytical robustness

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          Abstract

          We present approaches to facilitate the use of microfluidics outside of the laboratory, in our case within a clinical setting and monitoring from human subjects, where the complexity of microfluidic devices requires high skill and expertise and would otherwise limit translation. Microfluidic devices show great potential for converting complex laboratory protocols into on-chip processes. We demonstrate a flexible microfluidic platform can be coupled to microfluidic biosensors and used in conjunction with clinical microdialysis. The versatility is demonstrated through a series of examples of increasing complexity including analytical processes relevant to a clinical environment such as automatic calibration, standard addition, and more general processes including system optimisation, reagent addition and homogenous enzyme reactions. The precision and control offered by this set-up enables the use of microfluidics by non-experts in clinical settings, increasing uptake and usage in real-world scenarios. We demonstrate how this type of system is helpful in guiding physicians in real-time clinical decision-making.

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          Most cited references32

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          Droplet microfluidics.

          Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of "digital fluidic" operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as microreactors ranging from the nano- to femtoliter range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. This review will focus on the various droplet operations, as well as the numerous applications of the system. Due to advantages unique to droplet-based systems, this technology has the potential to provide novel solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.
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            Lab-on-Skin: A Review of Flexible and Stretchable Electronics for Wearable Health Monitoring.

            Skin is the largest organ of the human body, and it offers a diagnostic interface rich with vital biological signals from the inner organs, blood vessels, muscles, and dermis/epidermis. Soft, flexible, and stretchable electronic devices provide a novel platform to interface with soft tissues for robotic feedback and control, regenerative medicine, and continuous health monitoring. Here, we introduce the term "lab-on-skin" to describe a set of electronic devices that have physical properties, such as thickness, thermal mass, elastic modulus, and water-vapor permeability, which resemble those of the skin. These devices can conformally laminate on the epidermis to mitigate motion artifacts and mismatches in mechanical properties created by conventional, rigid electronics while simultaneously providing accurate, non-invasive, long-term, and continuous health monitoring. Recent progress in the design and fabrication of soft sensors with more advanced capabilities and enhanced reliability suggest an impending translation of these devices from the research lab to clinical environments. Regarding these advances, the first part of this manuscript reviews materials, design strategies, and powering systems used in soft electronics. Next, the paper provides an overview of applications of these devices in cardiology, dermatology, electrophysiology, and sweat diagnostics, with an emphasis on how these systems may replace conventional clinical tools. The review concludes with an outlook on current challenges and opportunities for future research directions in wearable health monitoring.
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              Emerging Droplet Microfluidics.

              Droplet microfluidics generates and manipulates discrete droplets through immiscible multiphase flows inside microchannels. Due to its remarkable advantages, droplet microfluidics bears significant value in an extremely wide range of area. In this review, we provide a comprehensive and in-depth insight into droplet microfluidics, covering fundamental research from microfluidic chip fabrication and droplet generation to the applications of droplets in bio(chemical) analysis and materials generation. The purpose of this review is to convey the fundamentals of droplet microfluidics, a critical analysis on its current status and challenges, and opinions on its future development. We believe this review will promote communications among biology, chemistry, physics, and materials science.
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                Author and article information

                Journal
                101128948
                31848
                Lab Chip
                Lab Chip
                Lab on a chip
                1473-0197
                1473-0189
                7 June 2020
                10 July 2019
                07 August 2019
                29 June 2020
                : 19
                : 15
                : 2537-2548
                Affiliations
                [a. ]Department of Bioengineering, Imperial College, London.
                [b. ]Department of Basic and Clinical Neuroscience, Kings College London.
                [c. ]Institute of Biomedical Engineering, Facuulty of Medicine, Prince of Songkla University, Hat Yai, Thailand
                Author notes

                Author contributions

                SG, MLR, MAB, CLL, ICS and TP worked on developing the technology. SG and MLR planned and carried out the experiments and wrote and revised the manuscript. MAB planned and carried out the ascorbate removal experiments and revised the manuscript. CLL and ICS were involved in collection of clinical TBI patient data and revised the manuscript. TP revised the manuscript. SLJ, CP and AJS facilitated gathering of patient data and revised the manuscript. MGB planned experiments and wrote and revised the manuscript. Microfluidic platform, automatic calibration setup and pyruvate detection are described in patent application number: US20180136247A1, published 2018, Imperial Innovations (inventors: M. G. Boutelle, M. L. Rogers, C. L. Leong and S. A. N. Gowers).

                [*]

                Contributed equally to the work

                Article
                PMC7321805 PMC7321805 7321805 nihpa1601245
                10.1039/c9lc00400a
                7321805
                31290529
                1ef20e32-d246-4347-9fd9-ae5ba5951268
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