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.