Microfluidic Gastrointestinal Cell Culture Technologies-Improvements in the Past Decade.

Gastrointestinal cell culture technology has evolved in the past decade with the integration of microfluidic technologies, bringing advantages with greater selectivity and cost effectiveness. Herein, these technologies are sorted into three categories, namely the cell-culture insert devices, conventional microfluidic devices, and 3D-printed microfluidic devices. Each category is discussed in brief with improvements also discussed here.

Label-Free Single Microparticles and Cell Aggregates Sorting in Continuous Cell-Based Manufacturing.

There is a paradigm shift in biomanufacturing toward continuous bioprocessing but cell-based manufacturing using adherent and suspension cultures, including microcarriers, hydrogel microparticles, and 3D cell aggregates, remains challenging due to the lack of efficient in-line bioprocess monitoring and cell harvesting tools. Herein, a novel label-free microfluidic platform for high throughput (≈50 particles/sec) impedance bioanalysis of biomass, cell viability, and stem cell differentiation at single particle resolution is reported. The device is integrated with a real-time piezo-actuated particle sorter based on user-defined multi-frequency impedance signatures.

Rapid Screening of Urinary Tract Infection Using Microfluidic Inertial-Impedance Cytometry.

Urinary tract infection (UTI) diagnosis based on urine culture for bacteriuria analysis is time-consuming and often leads to wastage of hospital resources due to false-positive UTI cases. Direct cellular phenotyping (e.g.

Label-free microfluidic cell sorting and detection for rapid blood analysis.

Blood tests are considered as standard clinical procedures to screen for markers of diseases and health conditions. However, the complex cellular background (>99.9% RBCs) and biomolecular composition often pose significant technical challenges for accurate blood analysis.

3D printing biocompatible materials with Multi Jet Fusion for bioreactor applications.

In the evolving three-dimensional (3D) printing technology, the involvement of different materials in any new 3D printing process necessitates a thorough evaluation of the product's biocompatibility for biomedical application. Here, we examined the ability of Multi Jet Fusion (MJF)-printed PA-12 to support cell proliferation and osteogenesis. Our results show that leachate from MJF-printed PA-12 does not inhibit the growth of L929 fibroblast and MC3T3e1 osteoblast.

Microfluidic Impedance-Deformability Cytometry for Label-Free Single Neutrophil Mechanophenotyping.

The intrinsic biophysical states of neutrophils are associated with immune dysfunctions in diseases. While advanced image-based biophysical flow cytometers can probe cell deformability at high throughput, it is nontrivial to couple different sensing modalities (e.g.

Acoustic Biosensors and Microfluidic Devices in the Decennium: Principles and Applications.

Lab-on-a-chip (LOC) technology has gained primary attention in the past decade, where label-free biosensors and microfluidic actuation platforms are integrated to realize such LOC devices. Among the multitude of technologies that enables the successful integration of these two features, the piezoelectric acoustic wave method is best suited for handling biological samples due to biocompatibility, label-free and non-invasive properties. In this review paper, we present a study on the use of acoustic waves generated by piezoelectric materials in the area of label-free biosensors and microfluidic actuation towards the realization of LOC and POC devices.

Realization of Three-Dimensionally MEMS Stacked Comb Structures for Microactuators Using Low-Temperature Multi-Wafer Bonding with Self-Alignment Techniques in CMOS-Compatible Processes.

A high-aspect-ratio three-dimensionally (3D) stacked comb structure for micromirror application is demonstrated by wafer bonding technology in CMOS-compatible processes in this work. A vertically stacked comb structure is designed to circumvent any misalignment issues that could arise from multiple wafer bonding. These out-of-plane comb drives are used for the bias actuation to achieve a larger tilt angle for micromirrors.

Application of a Machine Learning Algorithms in a Wrist-Wearable Sensor for Patient Health Monitoring during Autonomous Hospital Bed Transport.

Smart sensors, coupled with artificial intelligence (AI)-enabled remote automated monitoring (RAMs), can free a nurse from the task of in-person patient monitoring during the transportation process of patients between different wards in hospital settings. Automation of hospital beds using advanced robotics and sensors has been a growing trend exacerbated by the COVID crisis. In this exploratory study, a polynomial regression (PR) machine learning (ML) RAM algorithm based on a Dreyfusian descriptor for immediate wellbeing monitoring was proposed for the autonomous hospital bed transport (AHBT) application.

Application of Machine Learning Algorithm on MEMS-Based Sensors for Determination of Helmet Wearing for Workplace Safety.

Appropriate use of helmets as industrial personal protective gear is a long-standing challenge. The dilemma for any user wearing a helmet is thermal discomfort versus the chances of head injuries while not wearing it. Applying helmet microclimate psychrometry, we propose a logistic regression- (LR) based machine learning (ML) algorithm coupled with low-cost and readily available MEMS sensors to determine if a helmet was worn (W) or not worn (NW) by a human user.

Large-Scale Piezoelectric-Based Systems for More Electric Aircraft Applications.

A new approach in the development of aircraft and aerospace industry is geared toward increasing use of electric systems. An electromechanical (EM) piezoelectric-based system is one of the potential technologies that can produce a compactable system with a fast response and a high power density. However, piezoelectric materials generate a small strain, of around 0.

Bioactive micropatterned platform to engineer myotube-like cells from stem cells.

Skeletal muscle has the capacity to repair and heal itself after injury. However, this self-healing ability is diminished in the event of severe injuries and myopathies. In such conditions, stem cell-based regenerative treatments can play an important part in post-injury restoration.

Recapitulating atherogenic flow disturbances and vascular inflammation in a perfusable 3D stenosis model.

Blood vessel narrowing and arterial occlusion are pathological hallmarks of atherosclerosis, which involves a complex interplay of perturbed hemodynamics, endothelial dysfunction and inflammatory cascade. Herein, we report a novel circular microfluidic stenosis model that recapitulates atherogenic flow-mediated endothelial dysfunction and blood-endothelial cell (EC) interactions in vitro. 2D and 3D stenosis microchannels with different constriction geometries were fabricated using 3D printing to study flow disturbances under varying severity of occlusion and wall shear stresses (100 to 2000 dynecm).

A self-powered insulin patch pump with a superabsorbent polymer as a biodegradable battery substitute.

Highly popular insulin patch pumps have in-built non-removable batteries. These batteries are routinely disposed of together with the used pumps as medical waste and end up in landfills. This is an environmental contamination conundrum by design.

Integrated inertial-impedance cytometry for rapid label-free leukocyte isolation and profiling of neutrophil extracellular traps (NETs).

Circulating leukocytes are indispensable components of the immune system, and rapid analysis of their native state or functionalities can help to unravel their pathophysiological roles and identify novel prognostic biomarkers in health and diseases. Herein we report a novel high throughput "sample-in-answer-out" integrated platform for continuous leukocyte sorting and single-cell electrical profiling in a label-free manner. The multi-staged platform enables isolation of neutrophils and monocytes from diluted or lysed blood samples directly within minutes based on Dean flow fractionation (DFF) (stage 1).

Microhotplates for Metal Oxide Semiconductor Gas Sensor Applications-Towards the CMOS-MEMS Monolithic Approach.

The recent development of the Internet of Things (IoT) in healthcare and indoor air quality monitoring expands the market for miniaturized gas sensors. Metal oxide gas sensors based on microhotplates fabricated with micro-electro-mechanical system (MEMS) technology dominate the market due to their balance in performance and cost. Integrating sensors with signal conditioning circuits on a single chip can significantly reduce the noise and package size.

Label-free leukocyte sorting and impedance-based profiling for diabetes testing.

Circulating leukocytes comprise of approximately 1% of all blood cells and efficient enrichment of these cells from whole blood is critical for understanding cellular heterogeneity and biological significance in health and diseases. In this work, we report a novel microfluidic strategy for rapid (< 1 h) label-free leukocyte sorting and impedance-based profiling to determine cell activation in type 2 diabetes mellitus (T2DM) using whole blood. Leukocytes were first size-fractionated into different subtypes (neutrophils, monocytes, lymphocytes) using an inertial spiral sorter prior to single-cell impedance measurement in a microfluidic device with coplanar electrode design.

A tunable microfluidic 3D stenosis model to study leukocyte-endothelial interactions in atherosclerosis.

Atherosclerosis, a chronic inflammatory disorder characterized by endothelial dysfunction and blood vessel narrowing, is the leading cause of cardiovascular diseases including heart attack and stroke. Herein, we present a novel tunable microfluidic atherosclerosis model to study vascular inflammation and leukocyte-endothelial interactions in 3D vessel stenosis. Flow and shear stress profiles were characterized in pneumatic-controlled stenosis conditions (0%, 50% and 80% constriction) using fluid simulation and experimental beads perfusion.

A Novel Microdevice for Rapid Neutrophil Purification and Phenotyping in Type 2 Diabetes Mellitus.

Neutrophil dysfunction is strongly linked to type 2 diabetes mellitus (T2DM) pathophysiology, but the prognostic potential of neutrophil biomarkers remains largely unexplored due to arduous leukocyte isolation methods. Herein, a novel integrated microdevice is reported for single-step neutrophil sorting and phenotyping (chemotaxis and formation of neutrophil extracellular traps (NETosis)) using small blood volumes (fingerprick). Untouched neutrophils are purified on-chip from whole blood directly using biomimetic cell margination and affinity-based capture, and are exposed to preloaded chemoattractant or NETosis stimulant to initiate chemotaxis or NETosis, respectively.

Micro-engineered perfusable 3D vasculatures for cardiovascular diseases.

Vessel geometries in microengineered in vitro vascular models are important to recapitulate a pathophysiological microenvironment for the study of flow-induced endothelial dysfunction and inflammation in cardiovascular diseases. Herein, we present a simple and novel extracellular matrix (ECM) hydrogel patterning method to create perfusable vascularized microchannels of different geometries based on the concept of capillary burst valve (CBV). No surface modification is necessary and the method is suitable for different ECM types including collagen, matrigel and fibrin.

Negative Pressure Induced Droplet Generation in a Microfluidic Flow-Focusing Device.

We introduce an effective method to actively induce droplet generation using negative pressure. Droplets can be generated on demand using a series of periodic negative pressure pulses. Fluidic network models were developed using the analogy to electric networks to relate the pressure conditions for different flow regimes.

Rapid and label-free microfluidic neutrophil purification and phenotyping in diabetes mellitus.

Advanced management of dysmetabolic syndromes such as diabetes will benefit from a timely mechanistic insight enabling personalized medicine approaches. Herein, we present a rapid microfluidic neutrophil sorting and functional phenotyping strategy for type 2 diabetes mellitus (T2DM) patients using small blood volumes (fingerprick ~100 μL). The developed inertial microfluidics technology enables single-step neutrophil isolation (>90% purity) without immuno-labeling and sorted neutrophils are used to characterize their rolling behavior on E-selectin, a critical step in leukocyte recruitment during inflammation.

Low-cost, disposable microfluidics device for blood plasma extraction using continuously alternating paramagnetic and diamagnetic capture modes.

Blood plasma contains biomarkers and substances that indicate the physiological state of an organism, and it can be used to diagnose various diseases or body condition. To improve the accuracy of diagnostic test, it is required to obtain the high purity of blood plasma. This paper presents a low-cost, disposable microfluidics device for blood plasma extraction using magnetophoretic behaviors of blood cells.

3D printed microfluidics for biological applications.

The term "Lab-on-a-Chip," is synonymous with describing microfluidic devices with biomedical applications. Even though microfluidics have been developing rapidly over the past decade, the uptake rate in biological research has been slow. This could be due to the tedious process of fabricating a chip and the absence of a "killer application" that would outperform existing traditional methods.