TECHNOLOGY最新文献

Droplet actuation is an essential mechanism for droplet-based microfluidic systems. On-demand electromagnetic actuation is used in a ferrofluid-based microfluidic system for water droplet displacement. Electropermanent magnets (EPMs) are used to induce 50 mT magnetic fields in a ferrofluid filled microchannel with gradients up to 6.4 × 10⁴ kA/m². Short 50 µs current pulses activate the electropermanent magnets and generate negative magnetophoretic forces that range from 10 to 70 nN on 40 to 80 µm water-in-ferrofluid droplets. Maximum droplet displacement velocities of up to 300 µm/s are obtained under flow and no-flow conditions. Electropermanent magnet-activated droplet sorting under continuous flow is demonstrated using a split-junction microfluidic design.

In sickle cell disease (SCD), hemoglobin molecules polymerize intracellularly and lead to a cascade of events resulting in decreased deformability and increased adhesion of red blood cells (RBCs). Decreased deformability and increased adhesion of sickle RBCs lead to blood vessel occlusion (vaso-occlusion) in SCD patients. Here, we present a microfluidic approach integrated with a cell dimensioning algorithm to analyze dynamic deformability of adhered RBC at the single-cell level in controlled microphysiological flow. We measured and compared dynamic deformability and adhesion of healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs in blood samples obtained from 24 subjects. We introduce a new parameter to assess deformability of RBCs: the dynamic deformability index (DDI), which is defined as the time-dependent change of the cell's aspect ratio in response to fluid flow shear stress. Our results show that DDI of HbS-containing RBCs were significantly lower compared to that of HbA-containing RBCs. Moreover, we observed subpopulations of HbS containing RBCs in terms of their dynamic deformability characteristics: deformable and non-deformable RBCs. Then, we tested blood samples from SCD patients and analyzed RBC adhesion and deformability at physiological and above physiological flow shear stresses. We observed significantly greater number of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.

A central challenge in the field of metabolic engineering is the efficient identification of a metabolic pathway genotype that maximizes specific productivity over a robust range of process conditions. Here we review current methods for optimizing specific productivity of metabolic pathways in living cells. New tools for library generation, computational analysis of pathway sequence-flux space, and high-throughput screening and selection techniques are discussed.

We developed micromolded microwell arrays to study the proliferation and senescence of single cells. Microwell arrays were designed to be compatible with conventional cell culture protocols to simplify cell loading, cell culture, and imaging. We demonstrated the utility of these arrays by measuring the proliferation and senescence of isogenic cells which expressed or had been depleted of the human Werner syndrome protein. Our results allowed us to reveal cell-to-cell heterogeneity in proliferation in WRN+ and WRN-depleted fibroblasts during clonal growth.

The isolation of CD4 positive T lymphocyte (CD4+) from peripheral blood is important for monitoring patients after HIV infection. Here, we demonstrate a fast isolation strategy for CD4+ cells that involves mixing blood and glass microbubbles. After the specific binding of target cells to the microbubbles carrying specific antibodies on their surface, target cells will spontaneously float to the top of the blood vial and can be quickly separated. Using this strategy, we demonstrate that the isolation of CD4+ cells in less than 5 minutes and with better than 90% efficiency. This strategy for cell isolation based on buoyancy and glass microbubbles is quick and inexpensive, minimizes blood handling, does not require magnetic fields, or centrifugation equipment, and could lead to new, efficient strategies for AIDS diagnosis in resource-limited areas.

Dyes such as hematoxylin and eosin (H&E) and immunohistochemical stains have been increasingly used to visualize tissue composition in research and clinical practice. We present an alternative approach to obtain the same information using stain-free chemical imaging. Relying on Fourier transform infrared (FT-IR) spectroscopic imaging and computation, stainless computed histopathology can enable a rapid, digital, quantitative and non-perturbing visualization of morphology and multiple molecular epitopes simultaneously in a variety of research and clinical pathology applications.

The liver performs many key functions, the most prominent of which is serving as the metabolic hub of the body. For this reason, the liver is the focal point of many investigations aimed at understanding an organism's toxicological response to endogenous and exogenous challenges. Because so many drug failures have involved direct liver toxicity or other organ toxicity from liver generated metabolites, the pharmaceutical industry has constantly sought superior, predictive in-vitro models that can more quickly and efficiently identify problematic drug candidates before they incur major development costs, and certainly before they are released to the public. In this broad review, we present a survey and critical comparison of in-vitro liver technologies along a broad spectrum, but focus on the current renewed push to develop "organs-on-a-chip". One prominent set of conclusions from this review is that while a large body of recent work has steered the field towards an ever more comprehensive understanding of what is needed, the field remains in great need of several key advances, including establishment of standard characterization methods, enhanced technologies that mimic the in-vivo cellular environment, and better computational approaches to bridge the gap between the in-vitro and in-vivo results.

We combined microfluidic tools and molecular probes to monitor the migration speed of successive generations of cancer cells. We found that the migratory speed of individual cells changes stochastically from parent cells to their descendants, while the average speed of successive generations of cells remains constant. Further studies of the interrelations between cell migration and division processes may help identify the molecular determinants of cell speed and lead to new therapies to slow the invasion of cancer cells and delay metastases.