Skin-Integrated wearable systems and implantable biosensors: a comprehensive review

Biosensors devices have attracted the attention of many researchers across the world. They have the capability to solve a large number of analytical problems and challenges. They are future ubiquitous devices for disease diagnosis, monitoring, treatment and health management. This review presents an overview of the biosensors field, highlighting the current research and development of bio-integrated and implanted biosensors. These devices are micro- and nano-fabricated, according to numerous techniques that are adapted in order to offer a suitable mechanical match of the biosensor to the surrounding tissue, and therefore decrease the body’s biological response. For this, most of the skin-integrated and implanted biosensors use a polymer layer as a versatile and flexible structural support, combined with a functional/active material, to generate, transmit and process the obtained signal. A few challenging issues of implantable biosensor devices, as well as strategies to overcome them, are also discussed in this review, including biological response, power supply, and data communication.This research was funded by FCT- FUNDAÇÃO PARA A CIÊNCIA E TECNOLOGIA, grant numbers: PTDC/EMD-EMD/31590/2017 and PTDC/BTM-ORG/28168/2017

Flexible Electrochemical Lactate Sensor

Lactic acid is a vital indicator for shock, trauma, stress, and exercise intolerance. It is a key biomarker for increases in stress levels and is the primary metabolically produced acid responsible for tissue acidosis that can lead to muscle fatigue and weakness. During intensive exercise, the muscles go through anerobic metabolism to produce energy. This leads to decreases in the blood flow of nutrients and oxygen to the muscles and increases in lactate production, which in turn cause lactic acidosis. Currently, changes in blood lactate concentrations are monitored by sensors that can be invasive via blood or wearable based sensors that use the enzyme lactate oxidase. Lactate oxidase produces hydrogen peroxide, which is a toxic byproduct and can foul the surface of the sensor. Here, we present the development of a noninvasive wearable electrochemical lactate biosensor for the detection of lactic acid. The bioelectrode was designed with buckypaper (BP), which is composed of a dense network of multi-walled carbon nanotubes. This material was chosen due to its low cost, high conductivity, flexibility, and high active surface area. D-Lactate dehydrogenase (D-LDH) was immobilized on the surface of the BP to facilitate the oxidation of lactic acid. The biosensor was then integrated into a polydimethylsiloxane (PDMS) flexible substrate platform. PDMS was chosen because of its lightweight, flexible, biocompatibility, and conformal properties. The sensor is designed to be placed on skin in order to measure the concentration of lactate in sweat. The concentration of lactate in sweat has been shown to be a good biomarker for evaluating the severity of peripheral occlusive arterial diseases and damage in soft tissue. The lactate biosensor developed in this work exhibited a dynamic linear range of 5 mM to 45 mM lactic acid with a good sensitivity of 1.388μA/mMcm2. It can measure higher than the average lactate concentration in sweat during exercise, which is 31mM. This electrochemical biosensor has the potential to be used for the real-time detection of lactic acid concentration in sweat, suggesting promising applications in clinical, biological and sports medicine fields

Review—Lab-in-a-Mouth and Advanced Point-of-Care Sensing Systems: Detecting Bioinformation from the Oral Cavity and Saliva

Cavitas sensors and point-of-need sensors capable of providing physical and biochemical information from the oral cavity and saliva have attracted great attention because they offer remarkable advantages for noninvasive sensing systems. Herein, we introduce the basic anatomy and physiology of important body cavities to understand their characteristics as it is a pivotal foundation for the successful development of in-mouth devices. Next, the advanced development in lab-in-a-mouth sensors and point-of-need sensors for analyzing saliva are explained. In addition, we discuss the integrations of artificial intelligence and electronic technologies in smart sensing networks for healthcare systems. This review ends with a discussion of the challenges, future research trends, and opportunities in relevant disciplines. Mouthguard-based sensors and conventional salivary sensing devices will continue to be significant for the progress in the next-generation sensing technologies and smart healthcare systems.ope

Low-power Wearable Healthcare Sensors

Advances in technology have produced a range of on-body sensors and smartwatches that can be used to monitor a wearer’s health with the objective to keep the user healthy. However, the real potential of such devices not only lies in monitoring but also in interactive communication with expert-system-based cloud services to offer personalized and real-time healthcare advice that will enable the user to manage their health and, over time, to reduce expensive hospital admissions. To meet this goal, the research challenges for the next generation of wearable healthcare devices include the need to offer a wide range of sensing, computing, communication, and human–computer interaction methods, all within a tiny device with limited resources and electrical power. This Special Issue presents a collection of six papers on a wide range of research developments that highlight the specific challenges in creating the next generation of low-power wearable healthcare sensors

Pursuing precision in medicine and nutrition: the rise of electrochemical biosensing at the molecular level

In the era that we seek personalization in material things, it is becoming increasingly clear that the individualized management of medicine and nutrition plays a key role in life expectancy and quality of life, allowing participation to some extent in our welfare and the use of societal resources in a rationale and equitable way. The implementation of precision medicine and nutrition are highly complex challenges which depend on the development of new technologies able to meet important requirements in terms of cost, simplicity, and versatility, and to determine both individually and simultaneously, almost in real time and with the required sensitivity and reliability, molecular markers of different omics levels in biofluids extracted, secreted (either naturally or stimulated), or circulating in the body. Relying on representative and pioneering examples, this review article critically discusses recent advances driving the position of electrochemical bioplatforms as one of the winning horses for the implementation of suitable tools for advanced diagnostics, therapy, and precision nutrition. In addition to a critical overview of the state of the art, including groundbreaking applications and challenges ahead, the article concludes with a personal vision of the imminent roadmap.The financial support of PID2019-103899RBI00 (Spanish Ministerio de Ciencia e Innovación), and PMP22/00084, PI17CIII/00045, PI20CIII/00019 and PI22/00727 (AES-ISCIII) cofounded with FEDER funds Research Projects and the TRANSNANOAVANSENS-CM Program from the Comunidad de Madrid (Grant S2018/NMT-4349) are gratefully acknowledged. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.S

The examination of control entropy (CE) of triaxial accelerometry and lactate threshold in runners during treadmill exercise

The purpose of this study was to determine if the blood lactate threshold could be identified through the visual examination of the control entropy of high-resolution accelerometry in intercollegiate endurance runners (n=7). In procedures approved by the Eastern Michigan University College of Health and Human Services Human Subject Review Board, runners performed two lactate threshold tests to determine the relationship between the pace of running and the blood lactate concentration. High-resolution accelerometry (HRA) data as well as the metabolic cost of exercise was also collected during these trials. Control entropy (CE) analysis was conducted on the HRA of each individual plane of motion. Visual examination of the CE of the accelerations of the vertical and medio-lateral planes of motion revealed a relationship with the decline of CE, indicative of constraint, at paces which corresponded with an increase in blood lactate concentration of 1mmol/L above baseline

Development of wearable, screen-printable conductive polymer biosensors on flexible and textile substrates

Wearable biosensors have great potential for real-time diagnostics, but have been encumbered by costly fabrication processes, rigid materials, and inadequate sensitivity for physiological ranges. Sweat has hitherto been an understudied sample for measurement of components like pH and lactate, which can provide meaningful guidance for wound healing, eczema, and sports medicine applications. This thesis presents the development of a flexible, textile-based, screen-printed electrode system for biosensing applications. Furthermore, a flexible, pH-sensitive composite for textile substrates is developed by mixing polyaniline with dodecylbenzene sulfonic acid and textile screen-printing ink. The optimized composite’s pH response is compared to electropolymerized and drop-cast polyaniline sensors via open circuit potential measurements. A linear response is observed for all sensors between pH 3-10, with the composite demonstrating sufficient response time and a sensitivity better than -20 mV/pH, exceeding existing flexible screen-printed pH sensors. Investigations into a potentiometric, non-enzymatic lactate sensor using polyaminophenylboronic acid are also discussed

Microfluidic biosensor systems for real-time in vivo clinical bioanalysis

The aim of this thesis was to develop online biosensing systems for dialysate tissue metabo- lite detection in real time, to provide an insight into the health of tissue in various in vivo applications. An autocalibration system was developed using LabSmith programmable components to improve the accuracy of results obtained over long monitoring times. A method of col- lecting dialysate into storage tubes for online analysis while retaining temporal resolution was developed and validated. Microfluidic biosensor systems were developed for online measurement of glucose and lactate. One approach employed the use of biosensors, using a combined needle electrode with enzyme encapsulated in a hydrogel layer. The dynamic range of the biosensors was extended by adding an outer polyurethane layer. An alternative approach used automated syringe pumps and valves to develop a microfluidic system for in-flow enzyme addition to the dialysate stream. The existing rsMD system was applied for detection of tissue ischaemia during and after free flap surgery, by measuring dialysate glucose and lactate levels in real time. The system was able to detect flap failure, both during surgery and afterwards in the intensive therapy unit (ITU), much earlier than traditional methods. The rsMD system was adapted to enable monitoring of lactate levels in two dialysate streams and was applied for monitoring isolated porcine kidneys during two methods of cold preservation and subsequent re-warming. Significant differences in the lactate concentrations were observed between the two techniques. The system was extended for use with human transplant kidneys and with both porcine and human pancreases. A novel 3D printed wearable biosensor system was developed for direct integration with a clinical microdialysis probe. The system considerably improved the lag time and dispersional smearing compared with the existing rsMD system. The device was used in a proof-of-concept study with wireless potentiostats to monitor cyclists during exercise.Open Acces