Molecular crosstalk between intra-tumor blood vessels and tumor cells plays many critical roles in tumorigenesis and cancer metastasis. However, it has been very difficult to investigate the biochemical mechanisms underlying the overlapping, multifactorial processes that occur at the tumor-vascular interface using conventional murine models alone. Moreover, traditional two-dimensional (2D) culture models used in cancer research do not recapitulate aspects of the 3D tumor microenvironment. In the present study, we introduce a microfluidic model of the solid tumor-vascular interface composed of a human umbilical vein endothelial cell (HUVEC)-lined, perfusable, bioengineered blood vessel and tumor spheroids embedded in an extracellular matrix (ECM). We sought to optimize our model by varying the composition of the tumor spheroids (MDA-MB-231 breast tumor cells + mesenchymal stem cells (MSCs)/human lung fibroblasts (HLFs)/HUVECs) and the extracellular matrix (ECM: collagen, Matrigel, and fibrin gels with or without free HLFs) that we used. Our results indicate that culturing tumor spheroids containing MDA-MB-231 cells + HUVECs in an HLF-laden, fibrin-based ECM within our microfluidic device optimally (1) enhances the sprouting and migration of tumor spheroids, (2) promotes angiogenesis, (3) facilitates vascular invasion, and (4) preserves the structural integrity and functionality of HUVEC-lined microfluidic channels. This model may provide a platform for drug screening and mechanism studies on solid tumor interactions with functional blood vessels.

The liquid streams in a microchannel are hardly mixed to form laminar flow, and the mixing issue is well described by a low Reynolds number scheme. The staggered herringbone mixer (SHM) using repeated patterns of grooves in the microchannel have been proved to be an efficient passive micro-mixer. However, only a negative pattern of the staggered herringbone mixer has been used so far after it was first suggested, to the best of our knowledge. In this study, the mixing efficiencies from negative and positive staggered herringbone mixer patterns as well as from opposite flow directions were tested to investigate the effect of the micro-structure geometry on the surrounding laminar flow. The positive herringbone pattern showed better mixing efficiency than the conventionally used negative pattern. Also, generally used forward flow gives better mixing efficiency than reverse flow. The mixing was completed after two cycles of staggered herringbone mixer with both forward and reverse flow in a positive pattern. The traditional negative pattern showed complete mixing after four and five cycles in forward and reverse flow direction, respectively. The mixing effect in all geometries was numerically simulated, and the results confirmed more efficient mixing in the positive pattern than the negative. The results can further enable the design of a more efficient microfluidic mixer, as well as in depth understanding of the phenomena of positive and negative patterns existing in nature with regards to the surrounding fluids.

Ultrasonic treatment (UST) has been used not only to accelerate protein fibril growth and amplify infectious prion proteins from biological fluids, but also to break amyloid-like fibrils for treatment. Despite the applicability of UST to clinical treatment, both the decomposition characteristics of fibrils and the regrowth mechanisms of the decomposed fibrils remain unclear. Here, we report UST-driven decomposition of amyloid-like fibrils into shorter fibrils and the principles of fibril regrowth via conventional heating. Short fibrils decomposed by UST can be reconstructed into mature fibrils with the addition of monomeric protein, but the regrowth of short fibrils rarely occurs in the absence of monomeric protein. Interestingly, the reconstructed fibrils possess electric properties similar to those of the original fibrils. We propose a model that describes the regrowth process of amyloid-like fibrils decomposed by UST, which sheds light on future biomedical applications of UST for the treatment of amyloidogenic diseases.

Temperature increases during dielectrophoresis (DEP) can affect the response of biological entities, and ignoring the effect can result in misleading analysis. The heating mechanism of a DEP device is typically considered to be the result of Joule heating and is overlooked without an appropriate analysis. Our experiment and analysis indicate that the heating mechanism is due to the dielectric loss (Debye relaxation). A temperature increase between interdigitated electrodes (IDEs) has been measured with an integrated micro temperature sensor between IDEs to be as high as 70 °C at 1.5 MHz with a 30 V_pp applied voltage to our ultra-low thermal mass DEP device. Analytical and numerical analysis of the power dissipation due to the dielectric loss are in good agreement with the experiment data.

Triple-negative breast cancer (TNBC) is one of the most insidious forms of breast cancer with high rates of metastasis, resulting in major mortalities in breast cancer patients. To better understand and treat TNBC metastasis, investigation of TNBC interactions with blood vasculatures is crucial. Among multiple metastatic processes, a step of TNBC exit from the blood vessels (‘extravasation’) in the pre-metastatic organs determines the final site of the metastasis. Here, we present a rapid multilayer microfabrication method of transferring a three-dimensional (3D) overhang pattern to a substrate with a sacrificial layer to reconstitute a 3D blood vessel surrounded by the extracellular matrix containing organ-specific parenchymal cells. Bones and lungs are the most common sites of breast cancer metastasis. We modeled organotropic bone and lung metastasis in TNBC by introducing subpopulations of TNBC metastases into a vessel lumen surrounded by osteoblasts, bone marrow derived mesenchymal stem cells, and lung fibroblasts. We found that bone-like microenviroment with osteoblasts and mesenchymal stem cells promoted extravasation of the bone-tropic TNBC cells, whereas the lung-like microenviroment promoted extravasation of the lung-tropic TNBC cells. Given that these organ-specific parenchymal cells do not impact vascular permeability, our results suggest that the parenchymal cells dictate selective extravasation of the bone-tropic or lung-tropic TNBC cells in our system.