Integration Of Microfluidics Research Articles

Electrochemical sensors for analyte in saliva: recent update

Purpose This review provides an overview of recent advances in electrochemical sensors for analyte detection in saliva, highlighting their potential applications in diagnostics and health care. The purpose of this paper is to summarize the current state of the field, identify challenges and limitations and discuss future prospects for the development of saliva-based electrochemical sensors. Design/methodology/approach The paper reviews relevant literature and research articles to examine the latest developments in electrochemical sensing technologies for saliva analysis. It explores the use of various electrode materials, including carbon nanomaterial, metal nanoparticles and conducting polymers, as well as the integration of microfluidics, lab-on-a-chip (LOC) devices and wearable/implantable technologies. The design and fabrication methodologies used in these sensors are discussed, along with sample preparation techniques and biorecognition elements for enhancing sensor performance. Findings Electrochemical sensors for salivary analyte detection have demonstrated excellent potential for noninvasive, rapid and cost-effective diagnostics. Recent advancements have resulted in improved sensor selectivity, stability, sensitivity and compatibility with complex saliva samples. Integration with microfluidics and LOC technologies has shown promise in enhancing sensor efficiency and accuracy. In addition, wearable and implantable sensors enable continuous, real-time monitoring of salivary analytes, opening new avenues for personalized health care and disease management. Originality/value This review presents an up-to-date overview of electrochemical sensors for analyte detection in saliva, offering insights into their design, fabrication and performance. It highlights the originality and value of integrating electrochemical sensing with microfluidics, wearable/implantable technologies and point-of-care testing platforms. The review also identifies challenges and limitations, such as interference from other saliva components and the need for improved stability and reproducibility. Future prospects include the development of novel microfluidic devices, advanced materials and user-friendly diagnostic devices to unlock the full potential of saliva-based electrochemical sensing in clinical practice.

Recent developments and future perspectives of microfluidics and smart technologies in wearable devices.

Wearable devices are gaining popularity in the fields of health monitoring, diagnosis, and drug delivery. Recent advances in wearable technology have enabled real-time analysis of biofluids such as sweat, interstitial fluid, tears, saliva, wound fluid, and urine. The integration of microfluidics and emerging smart technologies, such as artificial intelligence (AI), machine learning (ML), and Internet of Things (IoT), into wearable devices offers great potential for accurate and non-invasive monitoring and diagnosis. This paper provides an overview of current trends and developments in microfluidics and smart technologies in wearable devices for analyzing body fluids. The paper discusses common microfluidic technologies in wearable devices and the challenges associated with analyzing each type of biofluid. The paper emphasizes the importance of combining smart technologies with microfluidics in wearable devices, and how they can aid diagnosis and therapy. Finally, the paper covers recent applications, trends, and future developments in the context of intelligent microfluidic wearable devices.

Electrochemical sensing of B-complex vitamins: current challenges and future prospects with microfluidic integration.

Vitamins are crucial micronutrients found in limited quantities in food, living organisms, and soil. Since most vitamins are not produced within the human body, a lack of these essential nutrients can result in various physiological disorders. Analyzing vitamins typically involves costly, time-consuming methods, requiring skilled personnel, automated equipment, and dedicated laboratory setups. The pressing need is for the development of efficient, portable, and user-friendly detection techniques that are cost-effective, addressing the challenges associated with traditional analytical approaches. In recent years, electrochemical sensors and electrochemical microfluidic devices have garnered prominence owing to their remarkable sensitivity, quick analysis, cost-effectiveness, and facile fabrication procedures. Electrochemical sensing and microfluidics are two distinct fields that are often integrated to create powerful and versatile sensing devices. The connection between them leverages the advantages of both fields to create highly efficient, miniaturized, and portable analytical systems. This interdisciplinary approach has led to the development of innovative devices with broad applications in various scientific, medical, and environmental domains. This review begins by outlining the importance of vitamins in human nutrition and health and emphasizing the need for precise and reliable sensing techniques. Owing to the limited literature available on electrochemical detection of vitamin B complexes, this review offers an in-depth analysis of modern electrochemical sensing of water-soluble vitamins, focusing on B1, B2, B6, B9, and B12. The challenges faced by researchers are addressed, including selectivity, sensitivity, interference, matrix effects, and calibration, while also exploring promising prospects such as nanomaterial integration, miniaturization, microfluidics-based IoTs, and innovative sensor designs.

(Invited) Biosensing for Biomanufacturing of Therapeutics

Contemporary process analytical technologies (PATs) for biomanufacturing are available for continuously monitoring a small set of analytical targets or are limited by costly and time-consuming offline efforts, which require extensive bioseparation, sample conditioning, and reagent handling. With the prime focus of the biopharmaceutical industry crystallizing around monoclonal antibodies and cell/gene therapies and the need for nimble, efficient production platforms, it is more relevant than ever to create scalable, in-line, and high throughput quantification methods to interrogate and direct the control of complex, stochastic processes during a production run. To realize such capabilities, there is a unique opportunity to "steal" from the extensive body of research and development in biosensors and assays for mobile diagnostics. In this lecture, I will assess the unique challenges that that arise in re-designing biosensors to meet the needs of online/in-line analytics in biomanufacturing and present examples of our research in the integration of microfluidics and electrochemical sensing for viral vector and other biologics production.

Rapid Information Retrieval from DNA Storage with Microfluidic Very Large-Scale Integration Platform.

Due to its high information density, DNA is very attractive as a data storage system. However, a major obstacle is the high cost and long turnaround time for retrieving DNA data with next-generation sequencing. Herein, the use of a microfluidic very large-scale integration (mVLSI) platform is described to perform highly parallel and rapid readout of data stored in DNA. Additionally, it is demonstrated that multi-state data encoded in DNA can be deciphered with on-chip melt-curve analysis, thereby further increasing the data content that can be analyzed. The pairing of mVLSI network architecture with exquisitely specific DNA recognition gives rise to a scalable platform for rapid DNA data reading.

Electrochemical Detection of Hormones Using Nanostructured Electrodes

Hormones regulate several physiological processes in living organisms, and their detection requires accuracy and sensitivity. Recent advances in nanostructured electrodes for the electrochemical detection of hormones are described. Nanostructured electrodes’ high surface area, electrocatalytic activity, and sensitivity make them a strong hormone detection platform. This paper covers nanostructured electrode design and production using MOFs, zeolites, carbon nanotubes, metal nanoparticles, and 2D materials such as TMDs, Mxenes, graphene, and conducting polymers onto electrodes surfaces that have been used to confer distinct characteristics for the purpose of electrochemical hormone detection. The use of aptamers for hormone recognition is producing especially promising results, as is the use of carbon-based nanomaterials in composite electrodes. These materials are optimized for hormone detection, allowing trace-level quantification. Various electrochemical techniques such as SWV, CV, DPV, EIS, and amperometry are reviewed in depth for hormone detection, showing the ability for quick, selective, and quantitative evaluation. We also discuss hormone immobilization on nanostructured electrodes to improve detection stability and specificity. We focus on real-time monitoring and tailored healthcare with nanostructured electrode-based hormone detection in clinical diagnostics, wearable devices, and point-of-care testing. These nanostructured electrode-based assays are useful for endocrinology research and hormone-related disease diagnostics due to their sensitivity, selectivity, and repeatability. We conclude with nanotechnology–microfluidics integration and tiny portable hormone-detection devices. Nanostructured electrodes can improve hormone regulation and healthcare by facilitating early disease diagnosis and customized therapy.

µPAD-based colorimetric nanogold aptasensor for CRP and IL-6 detection as sepsis biomarkers

Point-of-care testing is defined as medical diagnostic testing at or near the time and place of a patient. The integration of microfluidics with functionalized nanomaterials provides a rapid and sensitive detection method for biomarkers. Due to their optical characteristics, gold nanoparticles (GNPs) and aptamers can be used in a colorimetric technique. In this research, accurate and quick aptasensors were created using aptamers for two sepsis biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP). Aptamers were combined with GNPs to create aptasensors, which were then used to analyze various biomarker concentrations after aptamer-protein docking on the online HDOCK server to verify aptamer-protein interactions. To improve the results' stability and ease of use during the reaction time, microfluidic paper-based analytical devices (µPAD) was employed. The linear diagnostic ranges in this method were 50–1000 mg L−1 and 1–25 ng/L, and limit of detection values were 1.9 mg L−1 and 0.07 ng/L for CRP and IL-6, respectively; These values decreased when µPADs were used and became more suitable to diagnosis of sepsis. Two aptasensors were highly stable, reproducible, accurate, and recoverable. Our result suggests that colorimetric GNPs can be used to detect a specific analyte through color changes visible to the naked eye for monitoring purposes or as simple optical detectors for quantitative measurements.

Use and application of organ-on-a-chip platforms in cancer research.

Tumors are a major cause of death worldwide, and much effort has been made to develop appropriate anti-tumor therapies. Existing in vitro and in vivo tumor models cannot reflect the critical features of cancer. The development of organ-on-a-chip models has enabled the integration of organoids, microfluidics, tissue engineering, biomaterials research, and microfabrication, offering conditions that mimic tumor physiology. Three-dimensional in vitro human tumor models that have been established as organ-on-a-chip models contain multiple cell types and a structure that is similar to the primary tumor. These models can be applied to various foci of oncology research. Moreover, the high-throughput features of microfluidic organ-on-a-chip models offer new opportunities for achieving large-scale drug screening and developing more personalized treatments. In this review of the literature, we explore the development of organ-on-a-chip technology and discuss its use as an innovative tool in basic and clinical applications and summarize its advancement of cancer research.

Microfluidic integration of the single cell adhesion dot array (SCADA) technology for the real-time quantification of cell affinity

Understanding cell affinity to substrates and biomolecules is of great importance in disease research, drug development and general cell biology studies. Established techniques to measure cell affinity involve either expensive and cumbersome techniques that quantify the binding between cells and proteins in suspension (e.g., flow cytometry), or indirect methods that quantify the amount of cells on a surface (e.g., impedance sensors). Novel approaches exploit microtechnologies to reduce the number of cells needed and reach single cell resolution. However, the examples so far fail to provide a simple device to measure cell affinity with single cell resolution that can be adapted to several purposes and cell biology laboratories. Herein, we describe a tool for the real-time optical monitoring of cell affinity. It is based in the integration of the cell-based biosensing platform Single Cell Adhesion Dot Arrays (SCADA) into a microfluidic device. These SCADA-on-chip devices were used to successfully quantify and differentiate the affinity of human hair follicle-derived Mesenchymal Stem Cells towards several molecules with a range of cell-adhesive capabilities, which could be resolved in less than 20 min. The developed device constitutes a self-contained, single-use and user-friendly cell-based sensor for the quantification of cell affinity. Moreover, its multiple applications could be transferred to a great range of laboratories, whilst requiring a much reduced amount of reagents, cells and time to complete the assays.

An overview of the biosensing potential of organometallic compounds

Sensing technology is receiving increasing attention and improvements every day, making it a suggested component of personalized healthcare management. This is due to the capabilities of organometallic compounds supported by bioengineering. Organometallic compounds have abundant biological activity and many industrial and material science applications. Due to their unique biological targetability, they possess potential applications in drug development, diagnosis, and treatment. Organometallic compounds are emerging as promising candidates for the advancement in sensor technology as they are engineered to address some of the limitations encountered by their traditional counterparts. These compounds have distinctive characteristics that render them exceptionally responsive to alterations in their surroundings, hence enabling their use as sensors for the detection of diverse chemicals or circumstances. In addition, the adaptability of organometallic compounds allows for their incorporation into various sensor platforms, rendering them appropriate for a diverse array of applications such as environmental surveillance, medical analysis, and industrial assurance of quality. This review presents an overview of the recent progress made in the field of organometallic compounds’ design and production, specifically focusing on their potential uses as sensors. In addition, the structural modifications, functionalization procedures, integration of microfluidics, and the consequent effects on the sensing capacities of the materials are recalled. These bio-based approaches will align with sustainability objectives and make sensing more affordable, applicable, and successful.

Thermometric absorption spectroscopy through active locking of microbubble resonators

We implemented a Microbubble Resonator (MBRs) as an opto-thermal transducer to reconstruct the absorption spectrum of a nanoparticle suspension through its temperature increase. The experimental configuration features the MBR as both the vial containing the suspension and the optical transducer, allowing for a sensitive ultra-compact system with a straightforward microfluidic integration. With respect to a previous publication, the active lock of the MBR resonance produced an order-of-magnitude improvement in the system performance and a smooth absorption reconstruction. Additionally, since the detection process is temperature-based, the measurement is intrinsically insensitive towards scattering spectrum, both of the particles and of the host liquid. These features make the MBR system an interesting candidate for the characterisation of extremely small samples in the context of medical diagnosis from whole biological samples, quality controls for food safety or chemical production processes, and, in general, for the measurement of absorption in opaque mediums.

Demonstrating low Raman background in UV-written SiO2 waveguides.

Raman spectroscopy can give a chemical 'fingerprint' from both inorganic and organic samples, and has become a viable method of measuring the chemical composition of single biological particles. In parallel, integration of waveguides and microfluidics allows for the creation of miniaturized optical sensors in lab-on-a-chip devices. The prospect of combining integrated optics and Raman spectroscopy for Raman-on-chip offers new opportunities for optical sensing. A major limitation for this is the Raman background of the waveguide. This background is very low for optical fibers but remains a challenge for planar waveguides. In this work, we demonstrate that UV-written SiO2 waveguides, designed to mimic the performance of optical fibers, offer a significantly lower background than competing waveguide materials such as Si3N4. The Raman scattering in the waveguides is measured in absolute units and compared to that of optical fibers and Si3N4 waveguides. A limited study of the sensitivity of the Raman scattering to changes in pump wavelength and in waveguide design is also conducted. It is revealed that UV-written SiO2 waveguides offer a Raman background lower than -107.4 dB relative to a 785 nm pump and -106.5 dB relative to a 660 nm pump. Furthermore, the UV-written SiO2 waveguide demonstrates a 15 dB lower Raman background than a Si3N4 waveguide and is only 8.7 - 10.3 dB higher than optical fibers. Comparison with a polystyrene bead (in free space, diameter 7 µm) reveal an achievable peak SNR of 10.4 dB, showing the potential of UV-SiO2 as a platform for a Raman-on-chip device capable of measuring single particles.

A review of acoustofluidic separation of bioparticles.

Acoustofluidics is an emerging interdisciplinary research field that involves the integration of acoustics and microfluidics to address challenges in various scientific areas. This technology has proven to be a powerful tool for separating biological targets from complex fluids due to its label-free, biocompatible, and contact-free nature. Considering a careful designing process and tuning the acoustic field particles can be separated with high yield. Recently the advancement of acoustofluidics led to the development of point-of-care devices for separations of micro particles which address many of the limitations of conventional separation tools. This review article discusses the working principles and different approaches of acoustofluidic separation and provides a synopsis of its traditional and emerging applications, including the theory and mechanism of acoustofluidic separation, blood component separation, cell washing, fluorescence-activated cell sorting, circulating tumor cell isolation, and exosome isolation. The technology offers great potential for solving clinical problems and advancing scientific research.

(Invited) seamless Integration of Electronics, Electrochemistry, Microfluidics, and Materials for Next Generation Tissue-Integrated Sensors and Energy Devices

Recent advances in materials, mechanics, and device architectures form the foundations for rapidly emerging classes of sensors and energy devices with mechanical characteristics that allow for conformal interfaces with the soft, curvilinear surfaces of the human body. While the field of tissue-integrated biophysical sensors exhibits commendable progress in capturing clinical quality thermal, kinematic, and electrophysiological information, the advancement of complementary biochemical sensors severely lags due to unique challenges associated with seamless integration of delicate biochemical receptors, transducing components, and suitable packaging materials. Similarly, the vast majority of demonstrated tissue-mounted energy storage and energy harvesting systems unfortunately rely on toxic components that substantially diminish their attractiveness in bio-related applications. In this talk, I will discuss non-traditional approaches to address some of these grand challenges. Specifically, I will discuss three technologies that my lab is developing -1) wearable, self-powered sweat sensors for non-invasive health monitoring 2) wireless, implantable, battery-free sensors and optoelectronics for neuroscience research, and 3) fully resorbable batteries for broad applications in medicine and consumer electronics.

SERS Sensing of Dopamine with Fe(III)-Sensitized Nanogaps in Recleanable AuNP Monolayer Films.

Sensing of neurotransmitters (NTs) down to nm concentrations is demonstrated by utilizing self-assembled monolayers of plasmonic 60nm Au nanoparticles in close-packed arrays immobilized onto glass substrates. Multiplicative surface-enhanced Raman spectroscopy enhancements are achieved by integrating Fe(III) sensitizers into the precisely-defined <1nm nanogaps, to target dopamine (DA) sensing. The transparent glass substrates allow for efficient access from both sides of the monolayer aggregate films by fluid and light, allowing repeated sensing in different analytes. Repeated reusability after analyte sensing is shown through oxygen plasma cleaning protocols, which restore pristine conditions for the nanogaps. Examining binding competition in multiplexed sensing of two catecholamine NTs, DA and epinephrine, reveals their bidentate binding and their interactions. These systems are promising for widespread microfluidic integration enabling a wide range of continuous biofluid monitoring for applications in precision health.

Laser Controlled Manipulation of Microbubbles on a Surface with Silica-Coated Gold Nanoparticle Array.

Microbubble generation and manipulation play critical roles in diverse applications such as microfluidic mixing, pumping, and microrobot propulsion. However, existing methods are typically limited to lateral movements on customized substrates or rely on specific liquids with particular properties or designed concentration gradients, thereby hindering their practical applications. To address this challenge, this paperpresents a method that enables robust vertical manipulation of microbubbles. By focusing a resonant laser on hydrophilic silica-coated gold nanoparticle arrays immersed in water, plasmonic microbubbles are generated and detach from the substrates immediately upon cessation of laser irradiation. Using simple laser pulse control, it can achieve an adjustable size and frequency of bubble bouncing, which is governed by the movement of the three-phase contact line during surface wetting. Furthermore, it demonstrates that rising bubbles can be pulled back by laser irradiation induced thermal Marangoni flow, which is verified by particle image velocimetry measurements and numerical simulations. This study provides novel insights into flexible bubble manipulation and integration in microfluidics, with significant implications for various applications including mixing, drug delivery, and the development of soft actuators.

Toward microfluidic integration of respiratory and renal organ support in a single cartridge.

Extracorporeal organ assist devices provide lifesaving functions for acutely and chronically ill patients suffering from respiratory and renal failure, but their availability and use is severely limited by an extremely high level of operational complexity. While current hollow fiber-based devices provide high-efficiency blood gas transfer and waste removal in extracorporeal membrane oxygenation (ECMO) and hemodialysis, respectively, their impact on blood health is often highly deleterious and difficult to control. Further challenges are encountered when integrating multiple organ support functions, as is often required when ECMO and ultrafiltration (UF) are combined to deal with fluid overload in critically ill patients, necessitating an unwieldy circuit containing two separate cartridges. We report the first laboratory demonstration of simultaneous blood gas oxygenation and fluid removal in single microfluidic circuit, an achievement enabled by the microchannel-based blood flow configuration of the device. Porcine blood is flowed through a stack of two microfluidic layers, one with a non-porous, gas-permeable silicone membrane separating blood and oxygen chambers, and the other containing a porous dialysis membrane separating blood and filtrate compartments. High levels of oxygen transfer are measured across the oxygenator, while tunable rates of fluid removal, governed by the transmembrane pressure (TMP), are achieved across the UF layer. Key parameters including the blood flow rate, TMP and hematocrit are monitored and compared with computationally predicted performance metrics. These results represent a model demonstration of a potential future clinical therapy where respiratory support and fluid removal are both realized through a single monolithic cartridge.

Implantable photonic neural probes with 3D-printed microfluidics and applications to uncaging.

Advances in chip-scale photonic-electronic integration are enabling a new generation of foundry-manufacturable implantable silicon neural probes incorporating nanophotonic waveguides and microelectrodes for optogenetic stimulation and electrophysiological recording in neuroscience research. Further extending neural probe functionalities with integrated microfluidics is a direct approach to achieve neurochemical injection and sampling capabilities. In this work, we use two-photon polymerization 3D printing to integrate microfluidic channels onto photonic neural probes, which include silicon nitride nanophotonic waveguides and grating emitters. The customizability of 3D printing enables a unique geometry of microfluidics that conforms to the shape of each neural probe, enabling integration of microfluidics with a variety of existing neural probes while avoiding the complexities of monolithic microfluidics integration. We demonstrate the photonic and fluidic functionalities of the neural probes via fluorescein injection in agarose gel and photoloysis of caged fluorescein in solution and in fixed brain tissue.

Microfluidic Chips Fabrication and Integration for Tumor‐Derived Exosomes Detection

AbstractExosomes are a type of small extracellular vesicles carrying proteins, nucleic acids, and lipids. Because their expression levels are highly correlated with tumor development, exosomes are regarded as non‐invasive biomarkers for cancer diagnosis. Therefore, many exosome detection techniques are developed to provide a new way for cancer diagnosis. However, conventional techniques require the isolation of exosomes from body fluids before analysis, which usually relies on complex equipment and cumbersome operations. In addition, complex procedures may introduce impurities and thus affect the accuracy of the test. As an emerging analysis technology, microfluidic overcomes these shortcomings by integrating a microchannel for sample transport isolation and an exosome analysis module, showing great prospects in cancer diagnosis. This review will provide an overview of microchannel fabrication and analysis methods with outstanding compatibility for different microfluidic types, with a particular focus on microfluidic‐based exosome analysis methods that have the potential for clinical application.

Finger-Actuated Micropump of Constant Flow Rate without Backflow

This paper presents a finger-actuated micropump with a consistent flow rate and no backflow. The fluid dynamics in interstitial fluid (ISF) extraction microfluidics are studied through analytical, simulation, and experimental methods. Head losses, pressure drop, diodocity, hydrogel swelling, criteria for hydrogel absorption, and consistency flow rate are examined in order to access microfluidic performance. In terms of consistency, the experimental result revealed that after 20 s of duty cycles with full deformation on the flexible diaphragm, the output pressure became uniform and the flow rate remained at nearly constant levels of 2.2 μL/min. The flow rate discrepancy between the experimental and predicted flow rates is around 22%. In terms of diodicity, when the serpentine microchannel and hydrogel-assisted reservoir are added to the microfluidic system integration, the diodicity increases by 2% (Di = 1.48) and 34% (Di = 1.96), respectively, compared to when the Tesla integration (Di = 1.45) is used alone. A visual and experimentally weighted analysis finds no signs of backflow. These significant flow characteristics demonstrate their potential usage in many low-cost and portable microfluidic applications.