Next generation microfluidics: fulfilling the promise of lab-on-a-chip technologies.

Microfluidic lab-on-a-chip technologies enable the analysis and manipulation of small fluid volumes and particles at small scales and the control of fluid flow and transport processes at the microscale, leading to the development of new methods to address a broad range of scientific and medical challenges. Microfluidic and lab-on-a-chip technologies have made a noteworthy impact in basic, preclinical, and clinical research, especially in hematology and vascular biology due to the inherent ability of microfluidics to mimic physiologic flow conditions in blood vessels and capillaries. With the potential to significantly impact translational research and clinical diagnostics, technical issues and incentive mismatches have stymied microfluidics from fulfilling this promise.

Deciphering fibroblast-induced drug resistance in non-small cell lung carcinoma through patient-derived organoids in agarose microwells.

Patient-derived organoids (PDOs) serve as invaluable 3D tumor models, retaining the histological complexity and genetic heterogeneity found in primary tumors. However, the limitation of small sample volumes and the lack of tailored platforms have hindered the research using PDOs. Within the tumor microenvironment, cancer-associated fibroblasts play a pivotal role in influencing drug sensitivity.

Screen-Printed Sensors Modified with Nafion and Mesoporous Carbon for Electrochemical Detection of Lead in Blood.

Lead (Pb) has long been acknowledged as a systemic toxicant, with pronounced health impacts observed even at low exposure levels, particularly in children. Adverse effects include diminished cognitive function, altered behavior, and developmental delays. Consequently, it is imperative to conduct regular monitoring of Blood Lead Levels (BLLs).

trans-Endothelial neutrophil migration activates bactericidal function via Piezo1 mechanosensing.

The regulation of polymorphonuclear leukocyte (PMN) function by mechanical forces encountered during their migration across restrictive endothelial cell junctions is not well understood. Using genetic, imaging, microfluidic, and in vivo approaches, we demonstrated that the mechanosensor Piezo1 in PMN plasmalemma induced spike-like Ca signals during trans-endothelial migration. Mechanosensing increased the bactericidal function of PMN entering tissue.

Numerical Modeling of Physical Cell Trapping in Microfluidic Chips.

Microfluidic methods have proven to be effective in separation and isolation of cells for a wide range of biomedical applications. Among these methods, physical trapping is a label-free isolation approach that relies on cell size as the selective phenotype to retain target cells on-chip for follow-up analysis and imaging. In silico models have been used to optimize the design of such hydrodynamic traps and to investigate cancer cell transmigration through narrow constrictions.

Microfluidic isolation of breast cancer circulating tumor cells from microvolumes of mouse blood.

Liquid biopsy has shown significant research and clinical implications in cancer. Particularly, the isolation of circulating tumor cells (CTCs) in preclinical studies can provide crucial information about disease progression and therefore may guide treatment decisions. Microfluidic isolation systems have played a considerable role in CTC isolation for cancer studies, disease diagnosis, and prognosis.

Single Cell Analysis of Inertial Migration by Circulating Tumor Cells and Clusters.

Single-cell analysis provides a wealth of information regarding the molecular landscape of the tumor cells responding to extracellular stimulations, which has greatly advanced the research in cancer biology. In this work, we adapt such a concept for the analysis of inertial migration of cells and clusters, which is promising for cancer liquid biopsy, by isolation and detection of circulating tumor cells (CTCs) and CTC clusters. Using high-speed camera tracking live individual tumor cells and cell clusters, the behavior of inertial migration was profiled in unprecedented detail.

Manganese in residential drinking water from a community-initiated case study in Massachusetts.

Background: Manganese (Mn) is a metal commonly found in drinking water, but the level that is safe for consumption is unknown. In the United States (U.S.

Evolution of focused streams for viscoelastic flow in spiral microchannels.

Particle migration dynamics in viscoelastic fluids in spiral channels have attracted interest in recent years due to potential applications in the 3D focusing and label-free sorting of particles and cells. Despite a number of recent studies, the underlying mechanism of Dean-coupled elasto-inertial migration in spiral microchannels is not fully understood. In this work, for the first time, we experimentally demonstrate the evolution of particle focusing behavior along a channel downstream length at a high blockage ratio.

Three-dimensional lab-on-a-foil device for dielectrophoretic separation of cancer cells.

A simple, low-cost, three-dimensional (3D) lab-on-a-foil microfluidic device for dielectrophoretic separation of circulating tumor cells (CTCs) is designed and constructed. Disposable thin films are cut by xurography and microelectrode array are made with rapid inkjet printing. The multilayer device design allows the studying of spatial movements of CTCs and red blood cells (RBCs) under dielectrophoresis (DEP).

Determination of Mercury with a Miniature Sensor for Point-of-care Testing.

In developing countries, subsistence gold mining entails mixing metallic mercury with crushed sediments to extract gold. In this approach, the gold-mercury amalgam is heated to evaporate mercury and obtain gold. Thus, the highly volatile mercury can be absorbed through inhalation, resulting in adverse health effects.

Elasto-Inertial Focusing Mechanisms of Particles in Shear-Thinning Viscoelastic Fluid in Rectangular Microchannels.

Growth of the microfluidics field has triggered numerous advances in focusing and separating microparticles, with such systems rapidly finding applications in biomedical, chemical, and environmental fields. The use of shear-thinning viscoelastic fluids in microfluidic channels is leading to evolution of elasto-inertial focusing. Herein, we showed that the interplay between the elastic and shear-gradient lift forces, as well as the secondary flow transversal drag force that is caused by the non-zero second normal stress difference, lead to different particle focusing patterns in the elasto-inertial regime.

Automatic Microtitrator for Small Volume Samples.

Electroanalytical sensors for point-of-care biomedical or point-of-use environmental sample analysis are gaining popularity due to low limits of detection, ease of miniaturization, convenience, and ability to work with small sample volumes. Since pH must be tightly controlled for optimum electrochemical performance, adjustment of pH in these samples is often a necessity. Yet manual titration is time-consuming and can be especially challenging for small volumes.

Microfluidic techniques for isolation, formation, and characterization of circulating tumor cells and clusters.

Circulating tumor cell (CTC) clusters that are shed from the primary tumor into the bloodstream are associated with a poor prognosis, elevated metastatic potential, higher proliferation rate, and distinct molecular features compared to single CTCs. Studying CTC clusters may give us information on the differences in the genetic profiles, somatic mutations, and epigenetic changes in circulating cells compared to the primary tumor and metastatic sites. Microfluidic systems offer the means of studying CTC clusters through the ability to efficiently isolate these rare cells from the whole blood of patients in a liquid biopsy.

Electrochemical Determination of Manganese in Whole Blood with Indium Tin Oxide Electrode.

In this work, we demonstrate accurate and precise measurement of manganese (Mn) concentration in human whole blood with indium tin oxide (ITO) electrode using square wave stripping voltammetry. While an essential trace metal for human health, elevated levels of Mn due to environmental or occupational exposure have been associated with severe neuromotor dysfunction characterized by parkinsonism and cognitive dysfunction making the monitoring of Mn in whole blood necessary. Pediatric populations are particularly susceptible to Mn given their developing brain and potential long-term impacts on neurodevelopment.

Non-small cell lung carcinoma spheroid models in agarose microwells for drug response studies.

There is a growing interest in developing personalized treatment strategies for each cancer patient, especially those with non-small cell lung carcinoma (NSCLC) which annually accounts for the majority of cancer related deaths in the US. Yet identifying the optimal NSCLC treatment strategy for each cancer patient is critical due to a multitude of mutations, some of which develop following initial therapy and can result in drug resistance. A key difficulty in developing personalized therapies in NSCLC is the lack of clinically relevant assay systems that are suitable to evaluate drug sensitivity using a minuscule amount of patient-derived material available following biopsies.

Acoustic bubble for spheroid trapping, rotation, and culture: a tumor-on-a-chip platform (ABSTRACT platform).

Cancer is the leading cause of death globally, with 90% of deaths being caused by cancer metastasis. Circulating tumor cells (CTCs) play an important role in early diagnosis of cancer metastasis and in monitoring of therapeutic response. Therefore, reliable methods to isolate, collect and culture CTCs are required to obtain information on metastasis status and therapeutic treatment.

Molecular Activation of the Kv11.1 Channel Reprograms EMT in Colon Cancer by Inhibiting TGFβ Signaling via Activation of Calcineurin.

Control of ionic gradients is critical to maintain cellular homeostasis in both physiological and pathological conditions, but the role of ion channels in cancer cells has not been studied thoroughly. In this work we demonstrated that activity of the Kv11.1 potassium channel plays a vital role in controlling the migration of colon cancer cells by reversing the epithelial-to-mesenchymal transition (EMT) into the mesenchymal-to-epithelial transition (MET).

Polycarbonate Masters for Soft Lithography.

Fabrication of microfluidic devices by soft lithography is by far the most popular approach due to its simplicity and low cost. The approach relies on casting of elastomers, such as polydimethylsiloxane (PDMS), on masters fabricated from photoresists on silicon substrates. These masters, however, can be expensive, complicated to fabricate, and fragile.

Viscoelastic microfluidics: progress and challenges.

The manipulation of cells and particles suspended in viscoelastic fluids in microchannels has drawn increasing attention, in part due to the ability for single-stream three-dimensional focusing in simple channel geometries. Improvement in the understanding of non-Newtonian effects on particle dynamics has led to expanding exploration of focusing and sorting particles and cells using viscoelastic microfluidics. Multiple factors, such as the driving forces arising from fluid elasticity and inertia, the effect of fluid rheology, the physical properties of particles and cells, and channel geometry, actively interact and compete together to govern the intricate migration behavior of particles and cells in microchannels.

Mapping inertial migration in the cross section of a microfluidic channel with high-speed imaging.

The wide adoption of inertial microfluidics in biomedical research and clinical settings, such as rare cell isolation, has prompted the inquiry of its underlying mechanism. Although tremendous improvement has been made, the mechanism of inertial migration remains to be further elucidated. Contradicting observations are not fully reconciled by the existing theory, and details of the inertial migration within channel cross sections are missing in the literature.

Validation of Electrochemical Sensor for Determination of Manganese in Drinking Water.

Manganese (Mn) is an essential nutrient for metabolic functions, yet excessive exposure can lead to neurological disease in adults and neurodevelopmental deficits in children. Drinking water represents one of the routes of excessive Mn exposure. Both natural enrichment from rocks and soil, and man-made contamination can pollute groundwater that supplies drinking water for a substantial fraction of the U.

Resolving dynamics of inertial migration in straight and curved microchannels by direct cross-sectional imaging.

The explosive development of inertial microfluidic systems for label-free sorting and isolation of cells demands improved understanding of the underlying physics that dictate the intriguing phenomenon of size-dependent migration in microchannels. Despite recent advances in the physics underlying inertial migration, migration dynamics in 3D is not fully understood. These investigations are hampered by the lack of easy access to the channel cross section.

Microfluidic systems for hydrodynamic trapping of cells and clusters.

Microfluidic devices have been widely applied to trapping and isolation of cells and clusters for controllable intercellular environments and high-throughput analysis, triggering numerous advances in disease diagnosis and single-cell analysis. Passive hydrodynamic cell trapping is one of the simple and effective methods that has been gaining attention in recent years. Our aim here is to review the existing passive microfluidic trapping approaches, including microposts, microfiltration, microwells, and trapping chambers, with emphasis on design principles and performance.

Evaluation of Performance and Tunability of a Co-Flow Inertial Microfluidic Device.

Microfluidics has gained a lot of attention for biological sample separation and purification methods over recent years. From many active and passive microfluidic techniques, inertial microfluidics offers a simple and efficient method to demonstrate various biological applications. One prevalent limitation of this method is its lack of tunability for different applications once the microfluidic devices are fabricated.