1,721,005 research outputs found

    Brownian motion induced dynamic near-field interaction between quantum dots and plasmonic nanoparticles in aqueous medium

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    Metal-enhanced fluorescence has been studied over the past three decades in order to improve fluorescence sensing and imaging techniques in microfluidics and medical diagnostics. However, most of previous studies were performed while precisely maintaining the distance between fluorophore and plasmonic nanoparticles. In the present study, we investigate the enhanced fluorescence from quantum dots (QDs) that are mixed with plasmonic nanoparticles, such as gold nanoshell (GNS), in the aqueous medium without confining the interparticle distance. Although the near-field interaction could not occur based on the estimated interparticle distance according to particle concentrations, the experimental results indicate that the QD fluorescence can be greatly enhanced. A Monte Carlo simulation revealed that there exists considerable probability that QDs can reach the near-field region of GNS due to the thermally induced Brownian motion

    Directed Cell Migration Induced by Multiple Cues in the Engineered Microenvironment

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    Directed cancer cell migration induced by the environmental signals is a critical process in cancer metastasis. Cancer cells are exposed to complex chemical and mechanical signals stimulating directed migration in the tumor microenvironment, where the physical nature is highly complex. It is still barely understood how cells sense and process the complex environmental signals through the complex intercellular signaling networks to execute the cell responses. This study explores the migratory response of cancer cells under a single and combined signal. The driving hypothesis is that the cell innate capability constraints the signal stimulations physically in inducing directed cell migration. We assess the hypothesis by engineering the microenvironment in the microfluidic platform, exposing a single or combined signal environment. The combined signal environment is established by 1) two different chemoattractants (TGF-β1 and EGF) and 2) the convection-driven signal environment (TGF-β1 and interstitial flow). The results show that the performance of cancer cell directed migration is physically constrained when the environmental stimulation meets the cell’s innate physical limit. We illustrate the results in a physical and quantitative manner. This approach provides a novel insight to understand the cellular process and eventually enables to predict the cellular response under the complex environmental signals

    Effects of Thrombin on the Growth of Pancreatic Cancer Cells and Cancer Associated Fibroblasts Using a Microfluidic Model

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    Thrombotic events are known to be associated with various cancers and recent research has implicated parts of the coagulation system in promoting cancer progression. In particular, thrombin has been studied for its mitogenic effects in 2D cultures as well as in cancer progression in vivo in animal models however, conflicting results exist. Studies of proliferation in response to thrombin stimulation, of pancreatic cancer cells or pancreatic cancer-associated fibroblasts (CAFs) in vitro, that utilize a 3D culture platform are significantly limited. In this study, PDAC cancer cells and cancer-associated fibroblast (CAF) cells were exposed to thrombin using a microfluidic device that mimics in vivo conditions. The cells used herein were cultured in a microfluid device, suspended inside of a 3D collagen matrix, and exposed to daily stimulation of 1 U/mL of thrombin in serum-free media for one hour. The findings of this study are that there is no statistically significant effect, promotive or inhibitory, on the proliferation of the cells used in this study, these results were unexpected. At the end of this paper, a review of potential reasons as to why no significant effect was seen on the cells is presented

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Development of a Microfluidic Model of a Pancreatic Acinus

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    Pancreatic Ductal Adenocarcinoma (PDAC) continues to have a dismally low survival rate due to late diagnosis and poor treatment options. Therefore, there is a need to understand the early stages and progression of the disease. PDAC is known to have two types of cells of origin: ductal cells or acinar cells. Since acinar-derived PDAC is thought to be the more malignant of the two, it was chosen as the focus of this work. Most studies of acinar cells as they relate to PDAC are accomplished by using animal models such as genetically engineered mouse models. While this method yields a large amount of insight into the progression of the disease and the role of specific genes, it has the drawbacks of being very time and resource intensive. The quicker and less costly alternative is in vitro culture. Specifically, here we have developed a microfluidic model which can incorporate a key aspect of the extracellular matrix (ECM), type I collagen, and mimics the 3D geometry of an in vivo acinus. Most attempts at in vitro culture have been limited by the fact that isolated acinar cells show a decrease in the amount of digestive enzymes they secrete as culture continues. For this reason, we are using a reprogrammed cancer cell line. These cells can be induced with doxycycline to express PTF1a, which allows the cells to adapt acinar characteristics, such as the production of digestive enzymes. We were able to successfully culture and induce PTF1a in these cells within our chip. We showed that the cells exhibit no invasion into the collagen matrix once PTF1a is expressed, thus eliminating a key aspect of cancer cell culture. The cells grown in the chip are confirmed to be producing PRSS2, the digestive enzyme trypsinogen. Collectively, this suggests that we have produced healthy acinar cells growing in the same configuration that they would in vivo. This has many applications in the study of pancreatic ductal adenocarcinoma, as we have developed way to culture reprogramed cancer cells as their benign precursors and maintain acinar characteristics in vitro. It will also have applications in the study of many other pancreatic diseases by providing an in vitro model of a healthy, functional acinus

    Rapid characterization of drug response using tumor-microenvironment-on-chip

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    The use of microfluidic platforms has become an indispensable strategy to recapitulate physiological tumor microenvironment in order to describe cell and molecular biomechanics. To date, many promising early studies have characterized the role of the tumor microenvironment in cancer malignancy and investigated the efficacy of anti-cancer drugs. However, the essential in vivo conditions regulating tumor malignancy remains poorly understood. Additionally, the capability to predict the therapeutic efficacy of developed drugs is still limited. Consequently, a novel in vitro tumor model, entitled tumor-microenvironment on chip (TMOC), had been established to enable relevant in vivo tumor characterization within extracellular matrix (ECM) under physiological interstitial pressure and flow. In this study, TMOC was employed to investigate not only the role of regulation of tumor growth rate by 3D culture and interstitial flow but also the contribution of drug resistance to human tumors and drug binding, unbinding, and efflux rate constants in order to accelerate drug discovery. First of all, we found that growth rate comparison between monolayer (2D) and TMOC (3D) reflected that the role of extracellular matrix (ECM) was significant in tumor growth rate, however, the interstitial flow available on TMOC was not induce notable differences compared to tumors cultured without any flow. In the following study, exploring drug resistance in human cancer cells, we have observed that malignant MDA-MB-231 cells, triple negative and CD44 over-expressed human breast cancer cells were altered and became significantly resistant to doxorubicin(DOX) on TMOC compared with MCF-7 and SUM-159PT, whereas survival rate of MDA-MB-231 on 2D monolayer assays was significantly lower than MCF-7. Furthermore, in the case of DOX-loaded 250nm hyaluronic acid nanoparticles (HANP), which are designed to selectively bind to CD44 over-expressed cancer cells, the drug binding rate to MDA-MB-231 cells increased significantly compared to free DOX. Furthermore, a relatively higher drug unbinding and efflux rate was observed in DOX-HANP, accompanied by apparently higher survival rates compared to free DOX in spite of significantly more DOX-HANP accumulation in the cell area. This result infers that DOX-HANP is less able to facilitate drug binding to tumor nuclei. It may be because DOX-HANP was easily unbound from carrier protein due to its bigger size. Overall, these results suggest that the TMOC model is able to support the improved understanding of how tumors respond to anti-cancer drugs in vivo
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