Novel Sweat-Based Wearable Device for Advanced Monitoring of Athletic Physiological Biometrics.

Blood testing has traditionally been the gold standard for the physiological analysis and monitoring of professional athletes. In recent years, blood testing has moved out of the laboratory thanks to portable handheld devices, such as lactate meters. However, despite its usefulness and widespread use, blood testing has several drawbacks and limitations, such as the need for the athlete to stop exercising for blood extraction and the inability to have data continuously collected. In this scenario, sweat has become an alternative to blood testing because of its rich content of electrolytes and metabolites, as well as small quantities of sugars, proteins, and ions. Nevertheless, there are few devices capable of analyzing this biofluid and providing useful information to users. In this paper, an electronic system designed for the autonomous analysis of sweat electrolytes and metabolites along with heart rate dynamics is presented. This system is part of a novel wearable device tailored for athletes that offers to the user a real-time assessment of their physiological status and performance.

Mill Scale-Derived Magnetite Nanoparticles: A Novel Substrate for Lactate Oxidase-Based Biosensors.

Recycling and revalorization of waste are currently essential for sustainable growth. Mill scale, a waste product from steel production industries, which contains high levels of iron and minimal impurities, is proposed in this study as the source to synthesize magnetite nanoparticles (Fe3O4) for an enhancement of a lactate biosensor range. The synthesized Fe3O4 nanoparticles were coated with polydopamine (PDA) to prevent aggregation and degradation, creating a stable platform for immobilizing lactate oxidase enzyme (LOx) on their surfaces. The characterization of the Fe3O4@PDA material was carried out using transmission electron microscopy (TEM), dynamic light scattering (DLS), and measurement of the polydispersity index (PdI). The Fe3O4@PDA-LOx material was then deposited on a screen-printed carbon electrode modified with Prussian blue (SPCE-PB) for lactate detection. The biosensor exhibited a broad, dual linear concentration-response range, one from 0.1 to 4.62 mM with a limit of detection of 0.32 mM and sensitivity of 1.54 µAmM-1cm-2, and another one from 4.62 to 149.21 mM with a limit of detection of 6.31 mM and sensitivity of 0.08 µAmM-1cm-2. The dual-range concentration response of the biosensor makes it an ideal tool for lactate determination in various applications, including sports medicine, clinical diagnosis, and industrial bioprocessing.

Coupling Capillary-Driven Microfluidics with Lateral Flow Immunoassay for Signal Enhancement.

Microfluidics has emerged as a versatile technology that is applied to enhance the performance of analytical techniques, among others. Pursuing this, we present a capillary-driven microfluidic device that improves the sensitivity of lateral flow immunoassay rapid tests thanks to offering an automated washing step. A novel multilevel microfluidic chip was 3D-printed with a photocurable black resin, sealed by an optically clear pressure-sensitive adhesive, and linked to the lateral flow strip. To depict the efficacy of microfluidics and the washing step, cortisol was measured quantitatively within the proposed device. Measuring cortisol levels is a way to capture physiological stress responses. Among biofluids, saliva is less infectious and easier to sample than others. However, higher sensitivity is demanded because the salivary cortisol concentrations are much lower than in blood. We carried out a competitive lateral flow immunoassay protocol with the difference that the microfluidic device applies an automated washing step after the sample is drained downstream. It washes the trapped quantum-dot-labeled antibodies out from nitrocellulose, diminishing background noise as these are bonded to cortisols and not to the immobilized receptors. Fluorescence spectroscopy, as a high-precision analysis, was successfully applied to determine clinically relevant salivary cortisol concentrations within a buffer quantitatively. The microfluidic design relied on a 3D valve that avoids reagent cross-contamination. This cross-contamination could make the washing buffer impure and undesirably dilute the sample. The proposed device is cost-effective, self-powered, robust, and ideal for non-expert users.

Diffusion-free valve for preprogrammed immunoassay with capillary microfluidics.

By manipulating the geometry and surface chemistry of microfluidic channels, capillary-driven microfluidics can move and stop fluids spontaneously without external instrumentation. Furthermore, complex microfluidic circuits can be preprogrammed by synchronizing the capillary pressures and encoding the surface tensions of microfluidic chips. A key component of these systems is the capillary valve. However, the main concern for these valves is the presence of unwanted diffusion during the valve loading and activation steps that can cause cross-contamination. In this study, we design and validate a novel diffusion-free capillary valve: the π-valve. This valve consists of a 3D structure and a void area. The void acts as a spacer between two fluids to avoid direct contact. When the valve is triggered, the air trapped within the void is displaced by pneumatic suction induced from the capillary flow downstream without introducing a gas bubble into the circuit. The proposed design eliminates diffusive mixing before valve activation. Numerical simulation is used to study the function and optimize the dimensions of the π-valve, and 3D printing is used to fabricate either the mould or the microfluidic chip. A comparison with a conventional valve (based on a constriction-expansion valve) demonstrates that the π-valve eliminates possible backflow into the valve and reduces the mixing and diffusion during the loading and trigger steps. As a proof-of-concept, this valve is successfully implemented in a capillary-driven circuit for the determination of benzodiazepine, achieving the successive release of 3 solutions in a 3D-printed microfluidic chip without external instrumentation. The results show a 40% increase in the fluorescence intensity using the π-valve relative to the conventional value. Overall, the π-valve prevents cross-contamination, minimizes sample use, and facilitates a sophisticated preprogrammed release of fluids, offering a promising tool for conducting automated immunoassays applicable at point-of-care testing.

Capillary-driven microfluidics: impacts of 3D manufacturing on bioanalytical devices.

Over decades, decentralized diagnostics continues to move towards rapid and cost-effective testing at the point-of-care (POC). Although microfluidics has become a key enabling technology for POC testing, the need for robust peripheral equipment has been a key limiting factor in reaching an ideal device. Manufacturing technologies are now reaching a level of maturity that allows the definition of 3D features down to the sub-millimeter scale. Employing three-dimensional (3D) features and surface chemistry allows the possibility to pre-program sophisticated control of the capillary flow avoiding bulky peripheral equipment. By designing a sequence of steps, like elution of reagents, washing, mixing, and sensing, capillary valves have become a powerful tool for POC applications. These valves use capillary force to stop and then release flows within pre-programmed capillary circuits without any moving part. Without their 3D structure, the feasibility of creating pre-programmed bioanalytical devices would be nearly impossible. Besides, the advent of smart materials and their variety of surface properties permitted the unprecedented ability to fabricate reliable flow control with a range of capillary driving forces. The classification of such capillary elements is presented in two functional steps - stop and actuation. This review includes the advances in 3D microfabrication, design, and surface chemistry for manufacturing bioanalytical devices. These developments are critically reviewed, focusing on the process and considering phenomena such as timing, reproducibility, unwanted diffusion, and cross-contaminations.

Non-Invasive Multiparametric Approach To Determine Sweat-Blood Lactate Bioequivalence.

Many sweat-based wearable monitoring systems have been recently proposed, but the data provided by those systems often lack a reliable and meaningful relation to standardized blood values. One clear example is lactate, a relevant biomarker for both sports and health sectors, with a complex sweat-blood bioequivalence. This limitation decreases its individual significance as a sweat-based biomarker. Taking into account the insights of previous studies, a multiparametric methodology has been proposed to predict blood lactate from non-invasive independent sensors: sweat lactate, sweat rate, and heart rate. The bioequivalence study was performed with a large set of volunteers (>30 subjects) in collaboration with sports institutions (Institut Nacional d'Educació Física de Catalunya, INEFC, and Centre d'Alt Rendiment, CAR, located in Spain). A neural network algorithm was used to predict blood lactate values from the sensor data and subject metadata. The developed methodology reliably and accurately predicted blood lactate absolute values, only adding 0.3 mM of accumulated error when compared to portable blood lactate meters, the current gold standard for sports clinicians. The approach proposed in this work, along with an integrated platform for sweat monitoring, will have a strong impact on the sports and health fields as an autonomous, real-time, and continuous monitoring tool.

Enhanced Robustness of a Bridge-Type Rf-Mems Switch for Enabling Applications in 5G and 6G Communications.

In this paper, new suspended-membrane double-ohmic-contact RF-MEMS switch configurations are proposed. Double-diagonal (DDG) beam suspensions, with either two or three anchoring points, are designed and optimized to minimize membrane deformation due to residual fabrication stresses, thus exhibiting smaller mechanical deformation and a higher stiffness with more release force than previously designed single diagonal beam suspensions. The two-anchor DDGs are designed in two different orientations, in-line and 90°-rotated. The membrane may include a window to minimize the coupling to the lower electrode. The devices are integrated in a coplanar-waveguide transmission structure and fabricated using an eight-mask surface-micro-machining process on high-resistivity silicon, with dielectric-free actuation electrodes, and including glass protective caps. The RF-MEMS switch behavior is assessed from measurements of the device S parameters in ON and OFF states. The fabricated devices feature a measured pull-in voltage of 76.5 V/60 V for the windowed/not-windowed two-anchor DDG membranes, and 54 V/49.5 V for the windowed/not-windowed three-anchor DDG membranes, with a good agreement with mechanical 3D simulations. The measured ON-state insertion loss is better than 0.7 dB/0.8 dB and the isolation in the OFF state is better than 40 dB/31 dB up to 20 GHz for the in-line/90°-rotated devices, also in good agreement with 2.5D electromagnetic simulations.

Porous Cellulose Substrate Study to Improve the Performance of Diffusion-Based Ionic Strength Sensors.

Microfluidic paper-based analytical devices (µPADs) are leading the field of low-cost, quantitative in-situ assays. However, understanding the flow behavior in cellulose-based membranes to achieve an accurate and rapid response has remained a challenge. Previous studies focused on commercial filter papers, and one of their problems was the time required to perform the test. This work studies the effect of different cellulose substrates on diffusion-based sensor performance. A diffusion-based sensor was laser cut on different cellulose fibers (Whatman and lab-made Sisal papers) with different structure characteristics, such as basis weight, density, pore size, fiber diameter, and length. Better sensitivity and faster response are found in papers with bigger pore sizes and lower basis weights. The designed sensor has been successfully used to quantify the ionic concentration of commercial wines with a 13.6 mM limit of detection in 30 s. The developed µPAD can be used in quantitative assays for agri-food applications without the need for any external equipment or trained personnel.

Microfluidics and MEMS Technology for Membranes.

Nowadays manufacturing processes at nano and microscale provide reliable platform for the development of novel applications, specially in the membrane's field [...].

Flow Control in Porous Media: From Numerical Analysis to Quantitative µPAD for Ionic Strength Measurements.

Microfluidic paper-based analytical devices (µPADs) are a promising technology to enable accurate and quantitative in situ assays. Paper's inherent hydrophilicity drives the fluids without the need for external pressure sources. However, controlling the flow in the porous medium has remained a challenge. This study addresses this problem from the nature of the paper substrate and its design. A computational fluid dynamic model has been developed, which couples the characteristics of the porous media (fiber length, fiber diameter and porosity) to the fluidic performance of the diffusion-based µPAD sensor. The numerical results showed that for a given porous membrane, the diffusion, and therefore the sensor performance is affected not only by the substrate nature but also by the inlets' orientation. Given a porous substrate, the optimum performance is achieved by the lowest inlets' angle. A diffusion-based self-referencing colorimetric sensor was built and validated according to the design. The device is able to quantify the hydronium concentration in wines by comparison to 0.1-1.0 M tartaric acid solutions with a 41.3 mM limit of detection. This research showed that by proper adjustments even the simplest µPADs can be used in quantitative assays for agri-food applications.

Numerical and experimental analysis of a high-throughput blood plasma separator for point-of-care applications.

Blood plasma separation from undiluted blood is an essential step in many diagnostic procedures. This study focuses on the numerical optimization of the microfluidic blood plasma separator (BPS) and experimental validation of the results to achieve portable blood plasma separation with high purity and reasonable yield. The proposed design has two parts: a microchannel for blood processing and a tank below the aforementioned main channel for plasma collection. The study uses 3D computational fluid dynamic analysis to investigate the optimal ratio of heights between the top microchannel and the tank and their geometry at various flow rates. Thereafter, the results are compared with the experimental findings of the fabricated devices. These results are contrasted with some recent reported works to verify the proposed device's contribution to the improvement in the quality and quantity of the extracted plasma. The optimized design is capable of achieving a 19% yield with purity of 77.1%, depending on the requirement of the point-of-care (POC) application. These amounts could be tuned, for instance to 100% pure plasma, but the yield would decrease to 9%. In this study, the candidate application is hemostasis; therefore, the BPS is integrated to a biomimetic surface for hemostasis evaluation near the patients.

Recent Impact of Microfluidics on Skin Models for Perspiration Simulation.

Skin models offer an in vitro alternative to human trials without their high costs, variability, and ethical issues. Perspiration models, in particular, have gained relevance lately due to the rise of sweat analysis and wearable technology. The predominant approach to replicate the key features of perspiration (sweat gland dimensions, sweat rates, and skin surface characteristics) is to use laser-machined membranes. Although they work effectively, they present some limitations at the time of replicating sweat gland dimensions. Alternative strategies in terms of fabrication and materials have also showed similar challenges. Additional research is necessary to implement a standardized, simple, and accurate model representing sweating for wearable sensors testing.

Portable 3D-printed sensor to measure ionic strength and pH in buffered and non-buffered solutions.

A miniaturized 3D-printed device has been designed, manufactured and validated to perform as a low-cost sensor for compositional analysis of buffered and non-buffered solutions in industrial or remote areas. The proposed sensor takes advantage of the transport phenomenon and colorimetric measurements. The novel design can simultaneously detect the ionic strength of the solution by measuring the diffusion width of the ions and the pH by image analysis of the pH indicator color change. The results showed that it can detect pH variations of 0.25 and ionic measure difference of 0.1 M in non-buffer solutions. In addition, the design showed its adaptability to be used as a self-referencing sensor. The 3D-printed sensor presented here is not only successful in the evaluation of some important chemical characteristics but also brings flexibility, cost-effectiveness, swiftness and user-friendliness.

Advancements in Microfabricated Gas Sensors and Microanalytical Tools for the Sensitive and Selective Detection of Odors.

In recent years, advancements in micromachining techniques and nanomaterials have enabled the fabrication of highly sensitive devices for the detection of odorous species. Recent efforts done in the miniaturization of gas sensors have contributed to obtain increasingly compact and portable devices. Besides, the implementation of new nanomaterials in the active layer of these devices is helping to optimize their performance and increase their sensitivity close to humans' olfactory system. Nonetheless, a common concern of general-purpose gas sensors is their lack of selectivity towards multiple analytes. In recent years, advancements in microfabrication techniques and microfluidics have contributed to create new microanalytical tools, which represent a very good alternative to conventional analytical devices and sensor-array systems for the selective detection of odors. Hence, this paper presents a general overview of the recent advancements in microfabricated gas sensors and microanalytical devices for the sensitive and selective detection of volatile organic compounds (VOCs). The working principle of these devices, design requirements, implementation techniques, and the key parameters to optimize their performance are evaluated in this paper. The authors of this work intend to show the potential of combining both solutions in the creation of highly compact, low-cost, and easy-to-deploy platforms for odor monitoring.

Cost-effective microfabrication of sub-micron-depth channels by femto-laser anti-stiction texturing.

Micro Electro Mechanical Systems (MEMS) and microfluidic devices have found numerous applications in the industrial sector. However, they require a fast, cost-effective and reliable manufacturing process in order to compete with conventional methods. Particularly, at the sub-micron scale, the manufacturing of devices are limited by the dimensional complexity. A proper bonding and stiction prevention of these sub-micron channels are two of the main challenges faced during the fabrication process of low aspect ratio channels. Especially, in the case of using flexible materials such as polydimethylsiloxane (PDMS). This study presents a direct laser microfabrication method of sub-micron channels using an infrared (IR) ultrashort pulse (femtosecond), capable of manufacturing extremely low aspect ratio channels. These microchannels are manufactured and tested varying their depth from 0.5 µm to 2 µm and width of 15, 20, 25, and 30 µm. The roughness of each pattern was measured by an interferometric microscope. Additionally, the static contact angle of each depth was studied to evaluate the influence of femtosecond laser fabrication method on the wettability of the glass substrate. PDMS, which is a biocompatible polymer, was used to provide a watertight property to the sub-micron channels and also to assist the assembly of external microfluidic hose connections. A 750 nm depth watertight channel was built using this methodology and successfully used as a blood plasma separator (BPS). The device was able to achieve 100% pure plasma without stiction of the PDMS layer to the sub-micron channel within an adequate time. This method provides a novel manufacturing approach useful for various applications such as point-of-care devices.

Enhanced fully cellulose based forward and reverse blood typing assay.

This study presents an enhanced paper-based analytical device (PAD) for forward and reverse group blood typing. The proposed PAD uses a novel methodology, which provides highly reliable results on a fully cellulose based device. The PAD was printed on different cellulose substrates. These substrates were made of different cellulose fibers (sisal and eucalyptus), different grammages, refining steps, and wet additive content. Best parameters were chosen to achieve high reliability on both forward and reverse blood typing. The substrates were patterned with five hydrophilic channels and two hydrophobic areas. For reverse blood typing, the hemoagglutination reaction took place on the hydrophobic surface of the paper before being transferred to the paper web, where together with the forward blood typing tests were all washed with saline solution to read the results by elution. This device allows direct read-out of results; the stains show were agglutination happens. Different blood types were in full agreement between the reverse and forward method and in agreement with traditional methods. The time and simplicity of this methodology confirmed its utility.

A passive portable microfluidic blood-plasma separator for simultaneous determination of direct and indirect ABO/Rh blood typing.

The blood typing test is mandatory in any transfusion, organ transplant, and pregnancy situation. There is a lack of point-of-care (POC) blood typing that could perform both direct and indirect methods using a single droplet of whole blood. This study presents a new methodology combining a passive microfluidic blood-plasma separator (BPS) and a blood typing detector for the very first time, leading to a stand-alone microchip which is capable of determining the blood group from both direct and indirect methods simultaneously. The proposed design separates blood cells from plasma by applying hydrodynamic forces imposed on them, which overcomes the clogging issue and consequently maximizes the volume of the extracted plasma. An axial migration effect across the main channel is responsible for collecting the plasma in plasma collector channels. The BPS novel design approached 12% yield of plasma with 100% purity in approximately 10 minutes. The portable BPS was designed and fabricated to perform ABO/Rh blood tests based on the detection of agglutination in both antigens of RBCs (direct) and antibodies of plasma (indirect). The differences between agglutinated and non-agglutinated samples were distinguishable by the naked eye and also validated by particle analysis of microscopic pictures. The results of this passive BPS in ABO/Rh blood grouping verified the quality and quantity of the extracted plasma in practical applications.

Hemostasis-On-a-Chip: Impedance Spectroscopy Meets Microfluidics for Hemostasis Evaluation.

In the case of vascular injury, a complex process (of clotting) starts, involving mainly platelets and coagulation factors. This process in healthy humans is known as hemostasis, but when it is deregulated (thrombosis), it can be the cause of important cardiovascular diseases. Nowadays, the aging of the population and unhealthy lifestyles increase the impact of thrombosis, and therefore there is a need for tools to provide a better understanding of the hemostasis mechanisms, as well as more cost-effective diagnosis and control devices. This study proposes a novel microflow chamber, with interchangeable biomimetic surfaces to evaluate global hemostasis, using reduced amounts of blood sample and reagents, and also a minimized time required to do the test. To validate the performance of this novel device, a study on the new oral anticoagulant Apixaban (APIX) has been performed and compared to previous conventional techniques. The test shows an excellent agreement, while the amount of the required sample has been reduced (only 100 µL is used), and the amount of reagent as well. An imprinted electrode embedded in the chamber in order to measure the impedance during the coagulation process. This approach distinguishes the impedance behavior of plasma poor in platelets (PPP) and plasma rich in platelets (PRP) for the first time.

Novel applications of nonwood cellulose for blood typing assays.

Paper-based microfluidics devices can create a new healthcare model. Cellulose is carbohydrate polymer biocompatible and hydrophilic. These characteristics enhance the development of user-friendly diagnostic devices, but the link between paper manufacturing process and performance of the devices is still unclear. Previous studies focused on either commercial papers or lab papers from wood-cellulose fibers, with different basis-weight. This work introduces the effect of refining process and lab paper from nonwood-cellulose fibers, focusing on sisal fibers to overcome the aforementioned challenge. Structural characteristics of paper, such as basis-weight and degree of refining, are optimized and correlated with blood typing test resolution. Unrefined sisal paper of 50 g/m2 and 100 g/m2 basis-weight exhibit a higher gray intensity level than refined paper, and also maximal capillary rise and a pore size suitable for blood grouping tests. Two different blood types were evaluated with results consistent with the traditional methods, testifying the usefulness of this methodology. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1533-1541, 2019.

Novel Variable Radius Spiral⁻Shaped Micromixer: From Numerical Analysis to Experimental Validation.

A novel type of spiral micromixer with expansion and contraction parts is presented in order to enhance the mixing quality in the low Reynolds number regimes for point-of-care tests (POCT). Three classes of micromixers with different numbers of loops and modified geometries were studied. Numerical simulation was performed to study the flow behavior and mixing performance solving the steady-state Navier⁻Stokes and the convection-diffusion equations in the Reynolds range of 0.1⁻10.0. Comparisons between the mixers with and without expansion parts were made to illustrate the effect of disturbing the streamlines on the mixing performance. Image analysis of the mixing results from fabricated micromixers was used to verify the results of the simulations. Since the proposed mixer provides up to 92% of homogeneity at Re 1.0, generating 442 Pa of pressure drop, this mixer makes a suitable candidate for research in the POCT field.