Microfluidic devices can better control cellular microenvironments compared to conventional cell migration assays. Over the past few years, microfluidics-based chemotaxis studies showed a rapid growth. New strategies were developed to explore cell migration in manipulated chemical gradients. In addition to expanding the use of microfluidic devices for a broader range of cell types, microfluidic devices were used to study cell migration and chemotaxis in complex environments. Furthermore, high-throughput microfluidic chemotaxis devices and integrated microfluidic chemotaxis systems were developed for medical and commercial applications. In this article, we review recent developments in microfluidics-based chemotaxis studies and discuss the new trends in this field observed over the past few years.
Various types of chronic diseases (CD) are the leading causes of disability and death worldwide. While those diseases are chronic in nature, accurate and timely clinical decision making is critically required. Current diagnosis procedures are often lengthy and costly, which present a major bottleneck for effective CD healthcare. Rapid, reliable and low-cost diagnostic tools at point-of-care (PoC) are therefore on high demand. Owing to miniaturization, lab-on-chip (LoC) technology has high potential to enable improved biomedical applications in terms of low-cost, high-throughput, ease-of-operation and analysis. In this direction, research toward developing new LoC-based PoC systems for CD diagnosis is fast growing into an emerging area. Some studies in this area began to incorporate digital and mobile technologies. Here we review the recent developments of this area with the focus on chronic respiratory diseases (CRD), diabetes, and chronic kidney diseases (CKD). We conclude by discussing the challenges, opportunities and future perspectives of this field.
Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease characterized by breathing difficulty as a consequence of narrowed airways. Previous studies have shown that COPD is correlated with neutrophil infiltration into the airways through chemotactic migration. However, whether neutrophil chemotaxis can be used to characterize and diagnose COPD is not well established. In the present study, we developed a microfluidic platform for evaluating neutrophil chemotaxis to sputum samples from COPD patients. Our results show increased neutrophil chemotaxis to COPD sputum compared to control sputum from healthy individuals. The level of COPD sputum induced neutrophil chemotaxis was correlated with the patient’s spirometry data. The cell morphology of neutrophils in a COPD sputum gradient is similar to the morphology displayed by neutrophils exposed to an IL-8 gradient, but not a fMLP gradient. In competing gradients of COPD sputum and fMLP, neutrophils chemotaxis and cell morphology are dominated by fMLP.
Removing robust MRSA biofilms using magnetic nanoparticles (MNPs) under AC and DC magnetic field is demonstrated. Despite being non-toxic to planktonic bacteria, MNPs can bring damage to the extracellular matrix of biofilms and remove them from surfaces without inducing bacterial resistance.
Cardiovascular disease (CVD) and cancer are two leading causes of death worldwide. CVD and cancer share risk factors such as obesity and diabetes mellitus and have common diagnostic biomarkers such as interleukin-6 and C-reactive protein. Thus, timely and accurate diagnosis of these two correlated diseases is of high interest to both the research and healthcare communities. Most conventional methods for CVD and cancer biomarker detection such as microwell plate-based immunoassay and polymerase chain reaction often suffer from high costs, low test speeds, and complicated procedures. Recently, lab-on-a-chip (LoC)-based platforms have been increasingly developed for CVD and cancer biomarker sensing and analysis using various molecular and cell-based diagnostic biomarkers. These new platforms not only enable better sample preparation, chemical manipulation and reaction, high-throughput and portability, but also provide attractive features such as label-free detection and improved sensitivity due to the integration of various novel detection techniques. These features effectively improve the diagnostic test speed and simplify the detection procedure. In addition, microfluidic cell assays and organ-on-chip models offer new potential approaches for CVD and cancer diagnosis. Here we provide a mini-review focusing on recent development of LoC-based methods for CVD and cancer diagnostic biomarker measurements, and our perspectives of the challenges, opportunities and future directions.
When a constraint is removed, confluent cells migrate directionally into the available space. How the migration directionality and speed increase are initiated at the leading edge and propagate into neighboring cells are not well understood. Using a quantitative visualization technique — Particle Image Velocimetry (PIV) — we revealed that migration directionality and speed had strikingly different dynamics. Migration directionality increases as a wave propagating from the leading edge into the cell sheet, while the increase in cell migration speed is maintained only at the leading edge. The overall directionality steadily increases with time as cells migrate into the cell-free space, but migration speed remains largely the same. A Particle-Based Compass (PBC) model suggests cellular interplay (which depends on cell-cell distance) and migration speed are sufficient to capture the dynamics of migration directionality revealed experimentally. Extracellular Ca2+ regulated both migration speed and directionality, but in a significantly different way, suggested by the correlation between directionality and speed only in some dynamic ranges. Our experimental and modeling results reveal distinct directionality and speed dynamics in collective migration, and these factors can be regulated by extracellular Ca2+ through cellular interplay. Quantitative visualization using PIV and our PBC model thus provide a powerful approach to dissect the mechanisms of collective cell migration.
Microfluidics drives technological advancement in the point-of-care (POC) bioanalytical diagnostics towards portability, fast response and low cost. In the most microfluidic bioanalytical applications, flowing antigen/antibody reacts with immobilized antibody/antigen at...
Traditional diagnostic tests for chronic diseases are expensive and require a specialized laboratory, therefore limiting their use for point-of-care (PoC) testing. To address this gap, we developed a method for rapid and low-cost C-reactive protein (CRP) detection from blood by integrating a paper-based microfluidic immunoassay with a smartphone (CRP-Chip). We chose CRP for this initial development because it is a strong biomarker of prognosis in chronic heart and kidney disease. The microfluidic immunoassay is realized by lateral flow and gold nanoparticle-based colorimetric detection of the target protein. The test image signal is acquired and analyzed using a commercial smartphone with an attached microlens and a 3D-printed chip–phone interface. The CRP-Chip was validated for detecting CRP in blood samples from chronic kidney disease patients and healthy subjects. The linear detection range of the CRP-Chip is up to 2 μg/mL and the detection limit is 54 ng/mL. The CRP-Chip test result yields high reproducibility and is consistent with the standard ELISA kit. A single CRP-Chip can perform the test in triplicate on a single chip within 15 min for less than 50 US cents of material cost. This CRP-Chip with attractive features of low-cost, fast test speed, and integrated easy operation with smartphones has the potential to enable future clinical PoC chronic disease diagnosis and risk stratification by parallel measurements of a panel of protein biomarkers.
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