A PRECISION BRACHYTHERAPY DEVICE FOR THE TREATMENT OF ESOPHAGEAL CANCER

Project goal:​​ To design a precise brachytherapy device to deliver twice the radiation dose to cancerous tissue than to healthy tissue for patients with esophageal cancer. Brachytherapy is a form of radiation therapy in which a small radioactive seed is placed in close proximity to cancerous tissue in order to minimize damage to the healthy surrounding tissue. Non-specific brachytherapy exposure minimizes both treatment efficacy and maximum applied dose in the treatment of esophageal cancers. A precision brachytherapy device was sought after to improve patient care. A precision brachytherapy device utilizing multiple seed channels was created using materials compatible with gamma radiation used during the procedure, ethylene oxide for sterilization of the device, and diluted acid to simulate the conditions of the esophageal tract. Water and contrast mixture, used for visualization during a CT scan, were used to fill balloons which function to stabilize the device. The multiple seed channels were compatible with existing brachytherapy equipment and the device does not require additional training of radiation oncologists or medical physicists. Analysis proved that the device achieves twice the dose of radiation to cancerous tissue than healthy tissue in patients

Smartphone-Based Detection of Natural Killer Cells Using Flow-Based Measurement and Machine Learning Classification on Paper Microfluidics

Natural Killer (NK) cells are innate immune cells capable of cytotoxic activity that defends against viral infections and cancer, and as such, these cells have become attractive as cancer immunotherapies. Subpopulations of NK cells include CD56bright and CD56dim NK’s that perform either cytokine production or direct cytotoxic cell killing respectively, and the absolute number and proportion of these cells in peripheral blood is important in maintaining immune function. Current methods of performing analysis of the cytokine environment as well as the number and proportion of NK cell subpopulations includes the use of immunoassays, flow cytometry, and numerous fluorescent dyes, as well as highly specialized equipment. We have developed a smartphone based device for the prognostics of engineered NK cell therapy using a two component flow based paper microfluidic chip and machine learning classification. The first unit composed of grade 1 chromatography paper measures flow velocity via video to provide information on cytokine and total NK cell concentrations in undiluted buffy coat. The second, single flow lane unit performs spatial separation of CD56bright and CD56dim cells over its length using differential binding of anti-CD56 nanoparticles. A smartphone based fluorescent microscope was developed in combination with an graphical user interface to perform analysis of flow data as well as analysis of subpopulations via machine learning. Limits of detection for cytokine and cell concentrations were found to be 50IU and 1000 cells/mL respectively while classification accuracy for cell subpopulations was found to be 88%. Our device is capable of enabling prognostics for NK cell therapy from complex buffy coat samples in a uniquely low cost, easy to use, and point-of-care fashion

Plant-Based Scaffolds Modify Cellular Response to Drug and Radiation Exposure Compared to Standard Cell Culture Models

Plant-based scaffolds present many advantages over a variety of biomaterials. Recent studies explored their potential to be repopulated with human cells and thus highlight a growing interest for their use in tissue engineering or for biomedical applications. However, it is still unclear if thesein vitroplant-based scaffolds can modify cell phenotype or affect cellular response to external stimuli. Here, we report the characterization of the mechano-regulation of melanoma SK-MEL-28 and prostate PC3 cells seeded on decellularized spinach leaves scaffolds, compared to cells deposited on standard rigid cell culture substrate, as well as their response to drug and radiation treatment. The results showed that YAP/TAZ signaling was downregulated, cellular morphology altered and proliferation rate decreased when cells were cultured on leaf scaffold. Interestingly, cell culture on vegetal scaffold also affected cellular response to external stress. Thus, SK-MEL-28 cells phenotype is modified leading to a decrease in MITF activity and drug resistance, while PC3 cells showed altered gene expression and radiation response. These findings shed lights on the decellularization of vegetal materials to provide substrates that can be repopulated with human cells to better reproduce a soft tissue microenvironment. However, these complex scaffolds mediate changes in cell behavior and in order to exploit the capability of matching physical properties of the various plant scaffolds to diverse physiological functionalities of cells and human tissue constructs, additional studies are required to better characterize physical and biochemical cell-substrate interactions.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Smartphone based on-chip fluorescence imaging and capillary flow velocity measurement for detecting ROR1+ cancer cells from buffy coat blood samples on dual-layer paper microfluidic chip

Diagnosis of hematological cancer requires complete white blood cell count, followed by flow cytometry with multiple markers, and cytology. It requires substantial time and specialized training. A dual-layer paper microfluidic chip was developed as a quicker, low-cost, and field-deployable alternative to detect ROR1+ (receptor tyrosine-like orphan receptor one) cancer cells from the undiluted and untreated buffy coat blood samples. The first capture layer consisted of a GF/D glass fiber substrate, preloaded with cancer specific anti-ROR1 conjugated fluorescent particles to its center for cancer cell capture and direct smartphone fluorescence imaging. The second flow layer was comprised of a grade 1 cellulose chromatography paper with wax-printed four channels for wicking and capillary flow-based detection. The flow velocity was used as measure of antigen concentration in the buffy coat sample. In this manner, intact cells and their antigens were separated and independently analyzed by both imaging and flow velocity analyses. A custom-made smartphone-based fluorescence microscope and automated image processing and particle counter software were developed to enumerate particles on paper, with the limit of detection of 1 cell/mu L. Flow velocity analysis showed even greater sensitivity, with the limit of detection of 0.1 cells/mu L in the first 6 s of assay. Comparison with capillary flow model revealed great alignment with experimental data and greater correlation to viscosity than interfacial tension. Our proposed device Is able to capture and on-chip image ROR1+ cancer cells within a complex sample matrix (buffy coat) while simultaneously quantifying cell concentration in a point-of-care manner.24 month embargo; published online: 22 January 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Highly Reproducible Near-Field Optical Imaging with Sub-20-nm Resolution Based on Template-Stripped Gold Pyramids

ISSN:1936-0851ISSN:1936-086