Fully Autonomous Active Self-Powered Point-of-Care Devices: The Challenges and Opportunities.

Quick and effective point-of-care (POC) devices have the chance to revolutionize healthcare in developed and developing countries since they can operate anywhere the patient is, with the possibility of obtaining and sending the results to the doctor without delay. In recent years, significant efforts have focused on developing new POC systems that can screen for biomarkers continuously and non-invasively in body fluids to prevent, diagnose, and manage diseases. However, one of the critical challenges left to address is how to power them effectively and sufficiently. In developing countries and rural and remote areas, where there are usually no well-established electricity grids or nearby medical facilities, and using batteries is unreliable or not cost-effective, alternative power sources are the most challenging issue for stand-alone and self-sustained POC devices. Here, we provide an overview of the techniques for used self-powering POC devices, where the sample is used to detect and simultaneously generate energy to power the system. Likewise, this paper introduced the state-of-the-art with a review of different research projects, patents, and commercial products for self-powered POCs from the mid-2010s until present day.

High-efficient energy harvesting architecture for self-powered thermal-monitoring wireless sensor node based on a single thermoelectric generator.

In recent years, research on transducers and system architectures for self-powered devices has gained attention for their direct impact on the Internet of Things in terms of cost, power consumption, and environmental impact. The concept of a wireless sensor node that uses a single thermoelectric generator as a power source and as a temperature gradient sensor in an efficient and controlled manner is investigated. The purpose of the device is to collect temperature gradient data in data centres to enable the application of thermal-aware server load management algorithms. By using a maximum power point tracking algorithm, the operating point of the thermoelectric generator is kept under control while using its power-temperature transfer function to measure the temperature gradient. In this way, a more accurate measurement of the temperature gradient is achieved while harvesting energy with maximum efficiency. The results show the operation of the system through its different phases as well as demonstrate its ability to efficiently harvest energy from a temperature gradient while measuring it. With this system architecture, temperature gradients can be measured with a maximum error of 0.14 [Formula: see text]C and an efficiency of over 92% for values above 13 [Formula: see text]C and a single transducer.

Self-Powered Point-of-Care Device for Galvanic Cell-Based Sample Concentration Measurement.

A novel self-powered point-of-care low-power electronics approach for galvanic cell-based sample concentration measurement is presented. The electronic system harvests and senses at the same time from the single cell. The system implements a solution that is suitable in those scenarios where extreme low power is generated from the fuel cell. The proposed approach implements a capacitive-based method to perform a non-linear sweep voltammetry to the cell, but without the need to implement a potentiostat amplifier for that purpose. It provides a digital-user readable result without the need for external non-self-powered devices or instruments compared with other solutions. The system conception was validated for a particular case. The scenario consisted of the measurement of a NaCl solution as the electrolyte, which was related to the conductivity of the sample. The electronic reader continuously measured the current with a transfer function gain of 1.012 V mA-1. The overall system exhibited a maximum coefficient of variation of 6.1%, which was an improvement compared with the state-of-the-art. The proof of concept of this electronics system was validated with a maximum power consumption of 5.8 µW using commercial-off-the-self parts.

Effect of Temperature and Flow Rate on the Cell-Free Area in the Microfluidic Channel.

Blood cell manipulation in microdevices is an interesting task for the separation of particles, by their size, density, or to remove them from the buffer, in which they are suspended, for further analysis, and more. This study highlights the cell-free area (CFA) widening based on experimental results of red blood cell (RBC) flow, suspended in a microfluidic device, while temperature and flow rate incrementally modify RBC response within the microflow. Studies of human red blood cell flow, at a concentration of 20%, suspended in its autologous plasma and phosphate-buffered saline (PBS) buffer, were carried out at a wide flow rate, varying between 10 and 230 µL/min and a temperature range of 23 °C to 50 °C. The plotted measures show an increment in a CFA near the channel wall due to cell flow inertia after a constricted channel, which becomes more significant as temperature and flow rate increase. The temperature increment widened the CFA up to three times. In comparison, flow rate increment increased the CFA up to 20 times in PBS and 11 times in plasma.

An Integrated Detection Method for Flow Viscosity Measurements in Microdevices.

Point-of-care devices can analyze or characterize a sample in a short time. New technologies in medical science seek integrations of different measurement techniques for a complete analysis. This study describes the fabrication method, tests, and results of microtechnology as an approach for an integrated rheometer. The portable device measured the average flow velocity to calculate its viscosity. The whole system encompasses a microdevice integrated to a data acquisition system powered by USB and controlled by full custom software. As a result, we obtained an easy-to-handle and fabricate hand-held microrheometer. The device was tested using Newtonian fluids such as Mili-Q water, an aqueous solution of Ethylene-glycol at 40% and 25% and Non-Newtonian blood samples. The whole device can provide the non-linear viscosity of a 0.08 ml blood sample in less than 30 seconds, in a wide range of shear rate with an accuracy of 93%. More importantly, due to its detection method and simplicity, it can be enclosed within almost any fluidic microsystem, including biomedical applications.

Competitive USB-Powered Hand-Held Potentiostat for POC Applications: An HRP Detection Case.

Considerable efforts are made to develop Point-of-Care (POC) diagnostic tests. POC devices have the potential to match or surpass conventional systems regarding time, accuracy, and cost, and they are significantly easier to operate by or close to the patient. This strongly depends on the availability of miniaturized measurement equipment able to provide a fast and sensitive response. This paper presents a low-cost, portable, miniaturized USB-powered potentiostat for electrochemical analysis, which has been designed, fabricated, characterized, and tested against three forms of high-cost commercial equipment. The portable platform has a final size of 10.5 × 5.8 × 2.5 cm, a weight of 41 g, and an approximate manufacturing cost of $85 USD. It includes three main components: the power module which generates a stable voltage and a negative supply, the front-end module that comprises a dual-supply potentiostat, and the back-end module, composed of a microcontroller unit and a LabVIEW-based graphic user interface, granting plug-and-play and easy-to-use operation on any computer. The performance of this prototype was evaluated by detecting chronoamperometrically horseradish peroxidase (HRP), the enzymatic label most widely used in electrochemical biosensors. As will be shown, the miniaturized platform detected HRP at concentrations ranging from 0.01 ng·mL-1 to 1 µg·mL-1, with results comparable to those obtained with the three commercial electrochemical systems.

Self-Powered Portable Electronic Reader for Point-of-Care Amperometric Measurements.

In this work, we present a self-powered electronic reader (e-reader) for point-of-care diagnostics based on the use of a fuel cell (FC) which works as a power source and as a sensor. The self-powered e-reader extracts the energy from the FC to supply the electronic components concomitantly, while performing the detection of the fuel concentration. The designed electronics rely on straightforward standards for low power consumption, resulting in a robust and low power device without needing an external power source. Besides, the custom electronic instrumentation platform can process and display fuel concentration without requiring any type of laboratory equipment. In this study, we present the electronics system in detail and describe all modules that make up the system. Furthermore, we validate the device's operation with different emulated FCs and sensors presented in the literature. The e-reader can be adjusted to numerous current ranges up to 3 mA, with a 13 nA resolution and an uncertainty of 1.8%. Besides, it only consumes 900 µW in the low power mode of operation, and it can operate with a minimum voltage of 330 mV. This concept can be extended to a wide range of fields, from biomedical to environmental applications.

Electrochemical Instrumentation of an Embedded Potentiostat System (EPS) for a Programmable-System-On-a-Chip.

Under the main features required on portable devices in electrochemical instrumentation is to have a small size, low power consumption, economically affordable and precision in the measurements. This paper describes the development of a programmable Embedded Potentiostat System (EPS) capable of performing electrochemical sensing over system-on-a-chip platforms. Furthermore, the study explains a circuit design and develops some validation of the entire system. The hardware validation is performed by electrochemical experiments such as Double Step Chronoamperometry (DSC), Linear Sweep Voltammetry (LSV) and Cyclic Voltammetry (CV); moreover, a comparison of the experimental signals between a commercial potentiostat and the EPS was done by analysis of errors on the response signal. Results illustrate that the EPS is capable of handling currents in the range of absolute values of 86.44 to 3000 nA and having control voltages in the range of ±2 V. The device can support from 50 to 2000 samples per second. The EPS capabilities were compared with other compact potentiostats. The programmable EPS is an original approach which hugely reduces the hardware complexity and leads the way to create new applications for Point-of-Care or industrial developments with a reusable full electronics module.

'Plug-and-Power' Point-of-Care diagnostics: A novel approach for self-powered electronic reader-based portable analytical devices.

This paper presents an innovative approach in the portable Point-of-Care diagnostics field, the Plug-and-Power concept. In this new disposable sensor and plug-and-play reader paradigm, the energy required to perform a measurement is always available within the disposable test component. The reader unit contains all the required electronic modules to run the test, process data and display the result, but does not include any battery or power source. Instead, the disposable part acts as both the sensor and the power source. Additionally, this approach provides environmental benefits related to battery usage and disposal, as the paper-based power source has non-toxic redox chemistry that makes it eco-friendly and safe to follow the same waste stream as disposable test strips. The feasibility of this Plug-and-Power approach is demonstrated in this work with the development of a self-powered portable glucometer consisting of two parts: a test strip including a paper-based power source and a paper-based biofuel cell as a glucose sensor; and an application-specific battery-less electronic reader designed to extract the energy from the test strip, process the signal provided and show the glucose concentration on a display. The device was tested with human serum samples with glucose concentrations between 5 and 30 mM, providing quantitative results in good agreement with commercial measuring instruments. The advantages of the present approach can be extended to any kind of biosensors measuring different analytes and biological matrices, and in this way, strengthen the goals of Point-of-Care diagnostics towards laboratory decentralization, personalized medicine and improving patient compliance.

Combined Dielectrophoresis and Impedance Systems for Bacteria Analysis in Microfluidic On-Chip Platforms.

Bacteria concentration and detection is time-consuming in regular microbiology procedures aimed to facilitate the detection and analysis of these cells at very low concentrations. Traditional methods are effective but often require several days to complete. This scenario results in low bioanalytical and diagnostic methodologies with associated increased costs and complexity. In recent years, the exploitation of the intrinsic electrical properties of cells has emerged as an appealing alternative approach for concentrating and detecting bacteria. The combination of dielectrophoresis (DEP) and impedance analysis (IA) in microfluidic on-chip platforms could be key to develop rapid, accurate, portable, simple-to-use and cost-effective microfluidic devices with a promising impact in medicine, public health, agricultural, food control and environmental areas. The present document reviews recent DEP and IA combined approaches and the latest relevant improvements focusing on bacteria concentration and detection, including selectivity, sensitivity, detection time, and conductivity variation enhancements. Furthermore, this review analyses future trends and challenges which need to be addressed in order to successfully commercialize these platforms resulting in an adequate social return of public-funded investments.

Combined dielectrophoretic and impedance system for on-chip controlled bacteria concentration: Application to Escherichia coli.

The present paper reports a bacteria autonomous controlled concentrator prototype with a user-friendly interface for bench-top applications. It is based on a microfluidic lab-on-a-chip and its associated custom instrumentation, which consists of a dielectrophoretic actuator, to preconcentrate the sample, and an impedance analyzer, to measure concentrated bacteria levels. The system is composed of a single microfluidic chamber with interdigitated electrodes and an instrumentation with custom electronics. The prototype is supported by a real-time platform connected to a remote computer, which automatically controls the system and displays impedance data used to monitor the status of bacteria accumulation on-chip. The system automates the whole concentrating operation. Performance has been studied for controlled volumes of Escherichia coli samples injected into the microfluidic chip at constant flow rate of 10 µL/min. A media conductivity correcting protocol has been developed, as the preliminary results showed distortion of the impedance analyzer measurement produced by bacterial media conductivity variations through time. With the correcting protocol, the measured impedance values were related to the quantity of bacteria concentrated with a correlation of 0.988 and a coefficient of variation of 3.1%. Feasibility of E. coli on-chip automated concentration, using the miniaturized system, has been demonstrated. Furthermore, the impedance monitoring protocol had been adjusted and optimized, to handle changes in the electrical properties of the bacteria media over time.

An instantaneous low-cost point-of-care anemia detection device.

We present a small, compact and portable device for point-of-care instantaneous early detection of anemia. The method used is based on direct hematocrit measurement from whole blood samples by means of impedance analysis. This device consists of a custom electronic instrumentation and a plug-and-play disposable sensor. The designed electronics rely on straightforward standards for low power consumption, resulting in a robust and low consumption device making it completely mobile with a long battery life. Another approach could be powering the system based on other solutions like indoor solar cells, or applying energy-harvesting solutions in order to remove the batteries. The sensing system is based on a disposable low-cost label-free three gold electrode commercial sensor for 50 µL blood samples. The device capability for anemia detection has been validated through 24 blood samples, obtained from four hospitalized patients at Hospital Clínic. As a result, the response, effectiveness and robustness of the portable point-of-care device to detect anemia has been proved with an accuracy error of 2.83% and a mean coefficient of variation of 2.57% without any particular case above 5%.

Dielectrophoretic concentrator enhancement based on dielectric poles for continuously flowing samples.

We describe a novel continuous-flow cell concentrator microdevice based on dielectrophoresis, and its associated custom-made control unit. The performances of a classical interdigitated metal electrode-based dielectrophoresis microfluidic device and this enhanced version, that includes insulator-based pole structures, were compared using the same setup. Escherichia coli samples were concentrated at several continuous flows and the device's trapping efficiencies were evaluated by exhaustive cell counts. Our results show that pole structures enhance the retention up to 12.6%, obtaining significant differences for flow rates up to 20 µL/min, when compared to an equivalent classical interdigitated electrodes setup. In addition, we performed a subsequent proteomic analysis to evaluate the viability of the biological samples after the long exposure to the actuating electrical field. No Escherichia coli protein alteration in any of the two systems was observed.

Toward an anemia early detection device based on 50-µL whole blood sample.

A first approach to a portable and compact device for point-of-care (PoC) early instantaneous detection of anemia is described. This device works directly with whole blood samples relying on hematocrit analysis by means of impedance analysis. This device consists of a custom electronic instrumentation, postprocessing software and plug-and-play disposable sensor. The designed electronics are connected to a remote computer, which allows control of the instrumentation and results displaying with a user friendly software panel. The disposable sensor is based on a low-cost label-free three gold electrode commercial sensor for 50-µL volume samples. Forty-eight whole blood samples, randomly collected from hospitalized patients in Hospital Clínic, were used to validate the device capability for anemia detection. Whole blood samples were distributed in two groups: 10 samples for system calibration, and 38 samples for system validation. To calibrate the device, a complete EIS experiment has been performed to get a full impedance spectrum analysis, defining an accurate frequency working range for hematocrit detection. Afterward, we developed a protocol for instant impedance detection to determine the system detection accuracy, sensitivity, and coefficient of variation. As a result, impedance variations between different samples have been detected with less than 2% accuracy error for both impedance magnitude and phase. A hematocrit detection algorithm, relying on impedance analysis, has been developed based on the previous studies. The response, effectiveness, and robustness of the portable PoC device to detect anemia have been proved with an accuracy error of 1.75% and a coefficient of variation of less than 5%.

Design of a customized multipurpose nano-enabled implantable system for in-vivo theranostics.

The first part of this paper reviews the current development and key issues on implantable multi-sensor devices for in vivo theranostics. Afterwards, the authors propose an innovative biomedical multisensory system for in vivo biomarker monitoring that could be suitable for customized theranostics applications. At this point, findings suggest that cross-cutting Key Enabling Technologies (KETs) could improve the overall performance of the system given that the convergence of technologies in nanotechnology, biotechnology, micro&nanoelectronics and advanced materials permit the development of new medical devices of small dimensions, using biocompatible materials, and embedding reliable and targeted biosensors, high speed data communication, and even energy autonomy. Therefore, this article deals with new research and market challenges of implantable sensor devices, from the point of view of the pervasive system, and time-to-market. The remote clinical monitoring approach introduced in this paper could be based on an array of biosensors to extract information from the patient. A key contribution of the authors is that the general architecture introduced in this paper would require minor modifications for the final customized bio-implantable medical device.

Teragnosis in vivo: Innovación nanomédica fomentada por la convergencia de tecnologías emergentes / In-Vivo Theranostics: Nanomedicine innovation fostered by the convergence of emerging technologies

El creciente desarrollo y la mejora en cuanto a innovación de dispositivos basados en la convergencia de tecnologías emergentes ha dado lugar a un uso cada vez mayor de los nanosensores en la comunidad biomédica. Sin embargo, los nanosensores implantables aún tienen que afrontar ciertos retos como la biocompatibilidad y la seguridad de datos. En este artículo se abordan el progreso y los principales desafíos para esta clase de dispositivos nanomédicos y se analizan además las principales aplicaciones médicas con especial énfasis en la teragnosis, término que integra el concepto de diagnosis y terapia en un mismo dispositivo. De este modo, se traza el proceso desde la investigación aplicada hasta la comercialización del producto, que es cuando el retorno social puede ser estimado. Finalmente, se contempla la gestión de la tecnología dentro de un ecosistema de innovación, cuya cadena de valor incluye una integración multidisciplinaria y el flujo del conocimiento

The increasing development and the innovation improvement in devices based on the convergence of emerging technologies, have led into an increasing use of nanosensors in the biomedical community. However, implantable nanosensors still have to face some challenges as biocompatibility and data security. This article addresses the progress and the main challenges of these nanomedicine devices. Its medical applications are also analyzed with special emphasis on theragnosis, term that integrates the concepts of diagnostics and therapeutics in one single device. The process from applied research to commercialization, where the social return can be estimated, is being traced. Finally, the multidisciplinary participation and knowledge flow is analyzed in terms of an innovation ecosystem