Mobile Cloud-Based Blood Pressure Healthcare for Education

Mercury, pneumatic, and electronic sphygmomanometers were widely used for traditional blood pressure (BP) measurement. Cloud BP database, and mobile information and communication technology (MICT) do not integrate to these BP measurement methods. Pen and papers were employed to record BP values for nurses and physicians, and recording errors are possible to occur. In the chapter, the cloud-based BP platform solution and advanced wireless hospital BP measurement technologies were studied. These cloud-based BT measurement technologies were used as teaching aids to train students of electrical and nursing fields for mobile BP healthcare and health promotion education, and hence interdisciplinary teaching and learning were conducted. The teachers include professors of electrical and nursing fields, physicians, hospital nurses, and the engineer and health management experts of Microlife. The interdisciplinary teaching and learning of mobile BP healthcare and health promotion for smart aging were conducted in the Department of Nursing Division, Chang Cung Memorial Hospital, Keelung Branch, Department of Nursing Ching Kuo Institute of Management and Health, School of Nursing Chung Shan Medical University, and Department of Electrical Engineering, National Taiwan Ocean University. The students of electrical and nursing fields participated for joint interdisciplinary learning. The concepts of interdisciplinary mobile BP healthcare learning and teaching involve nursing and technology, healthy aging, BP health care for smart aging, telenursing, BP care for smart aging, community/home telecare, and MICT. The objective of teaching and learning is training the design and making electrical engineers to understand BP healthcare and health promotion, and nurses to understand mobile BP healthcare and health promotion system for smart aging

Integrated Microfluidic Molecular Diagnostics for Point-of-Care

Ideal point-of-care medical diagnostic devices are low cost assays capable of performing quantitative on-site rapid testing with high sensitivity and minimal manual steps. Current mainstream assays have several key limitations. Take, for instance, the common lateral flow assay—e.g. the pregnancy dipstick test. Such assays produce rapid results at low cost; however, they are mostly qualitative tests yielding only positive/negative results rather than quantitative figures. Other standard immunosorbant assays such as ELISA yield quantitative results but require several hours and extensive manual operation. At the other end of the spectrum, nucleic acid amplification techniques such as quantitative real-time PCR can deliver much higher sensitivity and selectivity. Unfortunately, these require costly equipment and several sample preparation steps. In this thesis, an integrated low-cost microfluidic chip and peripheral technologies for quantitative molecular diagnostics is described. These technical advances are designed to address the prevailing dilemmas described above. Researchers have developed and integrated several key components with microfluidic lab-on-chip miniaturization technology. In line with cutting-edge technology, a novel reagent patterning method, termed “digital micro-patterning”, was developed. A very simple method, it can be adopted at low-resource laboratory settings with mainstream equipment. Digital micro-patterning is unique in the sense that it can digitally pattern and concentrate reagents into highly defined micro-patterns. As a proof of concept, it was possible to pattern isothermal amplification reagents in hundreds of microwells and run amplification reactions in these wells. Next, a next-generation passive microfluidic pumping technology, termed the “vacuum battery system”, has been developed. This system allows for precise passive microfluidic pumping without external pumps, controls, or power sources for up to several hours. It does not require opaque fibers as in capillary systems (e.g. lateral flow assays), thus rendering this pumping method very attractive for optical detection platforms. The vacuum battery system is also significantly more robust compared to previous degas pumping techniques. Due to its portability, excellent optical properties, low cost, and the ability for complete integration with microfluidics, this platform technology opens exciting new opportunities to create a nouveau generation of standalone microfluidic chips readily operable in field settings. Additionally, a microfluidic sample preparation technology termed “digital plasma separation” has been developed. This technology uses parallel micro-cliff-like structures and gravity sedimentation to simultaneously separate plasma and compartmentalize samples into hundreds of micro-wells within minutes. Such sample preparation method enables isothermal digital nucleic acid amplification in one step. As a proof of concept, these technologies were integrated into a single microfluidic chip, termed the Integrated Molecular Diagnostics Chip (iMDx). This chip is capable of performing one-step quantitative nucleic acid detection directly from human whole blood samples (10~10^5 copies/ μl in 30 minutes). One low-cost disposable chip (~ $10) is designed to integrate and automate sample preparation, quantitative isothermal digital nucleic acid detection, and next generation autonomous microfluidic pumping. This portable integrated chip can acquire template concentration data similar to bench top real-time PCR machines. As the latter can cost three or more orders ($30~80k), this chip opens exciting opportunities for rapid point-of-care diagnostics in resource-low settings. Finally, in summarizing these cutting-edge methods, a blueprint for next-generation technical development plans is laid out. The key areas of focus are downstream microfluidic integration for advanced functionality such as protein and nucleic acid multiplexed detection on a single chip, telemedicine, mass production, and clinical studies in field settings. Ultimately, the implication of the research in this dissertation is that these platform technologies can be adopted into future medical diagnostic devices to enable rapid on-site quantitative molecular level detection at significantly lower costs. Both the system-level design rationale and component technologies developed herein provide promising building blocks for future point-of-care diagnostic assays

Single-Step Nanoplasmonic VEGF₁₆₅ Aptasensor for Early Cancer Diagnosis

Early cancer diagnosis is very important for the prevention or mitigation of metastasis. However, effective and efficient methods are needed to improve the diagnosis and assessment of cancer. Here, we report a single-step detection method using a nanoplasmonic aptamer sensor (aptasensor), targeting a vascular endothelial growth factor-165 (VEGF₁₆₅), a predominant biomarker of cancer angiogenesis. Our single-step detection is accomplished by (1) specific target recognition by an aptamer–target molecule interaction and (2) direct readouts of the target recognition. The readout is achieved by inactivation of surface plasmon enhancement of fluorescent probes preattached to the aptamers. Our aptasensor provides the appropriate sensitivity for clinical diagnostics with a wide range of linear detection from 25 pg/mL to 25 μg/mL (=from 1.25 pM to 1.25 μM), high specificity for VEGF₁₆₅ against PDGF-BB, osteopontin (OPN), VEGF₁₂₁, NaCl, and temporal/thermal/biological stability. In experiments with 100% serum and saliva from clinical samples, readouts of the aptasensor and an ELISA for VEGF₁₆₅ show good agreement within the limit of the ELISA kit. We envision that our developed aptasensor holds utilities for point-of-care cancer prognostics by incorporating simplicity in detection, low-cost for test, and required small sample volumes

Effect of De-Twinning on Tensile Strength of Nano-Twinned Cu Films

Tensile tests were carried on the electroplated Cu films with various densities of twin grain boundary. With TEM images and a selected area diffraction pattern, nano-twinned structure can be observed and defined in the electroplated Cu films. The density of the nano-twin grain structure can be manipulated with the concentration of gelatin in the Cu-sulfate electrolyte solution. We found that the strength of the Cu films is highly related to the twin-boundary density. The Cu film with a greater twin-boundary density has a larger fracture strength than the Cu film with a lesser twin-boundary density. After tensile tests, necking phenomenon (about 20 μm) occurred in the fractured Cu films. Moreover, by focused ion beam (FIB) cross-sectional analysis, the de-twinning can be observed in the region where necking begins. Thus, we believe that the de-twinning of the nano-twinned structure initiates the plastic deformation of the nano-twinned Cu films. Furthermore, with the analysis of the TEM images on the nano-twinned structure in the necking region of the fractured Cu films, the de-twinning mechanism attributes to two processes: (1) the ledge formation by the engagement of the dislocations with the twin boundaries and (2) the collapse of the ledges with the opposite twin-boundaries. In conclusion, the plastic deformation of nano-twinned Cu films is governed by the de-twinning of the nano-twinned structure. Moreover, the fracture strength of the nano-twinned Cu films is proportional to the twin-boundaries density

Effects of <i>ADAMTS14</i> genetic polymorphism and cigarette smoking on the clinicopathologic development of hepatocellular carcinoma

<div><p>Background</p><p><i>ADAMTS14</i> is a member of the ADAMTS (<u>a</u> <u>d</u>isintegrin <u>a</u>nd <u>m</u>etalloproteinase with <u>t</u>hrombo<u>s</u>pondin motifs), which are proteolytic enzymes with a variety of further ancillary domain in the C-terminal region for substrate specificity and enzyme localization via extracellular matrix association. However, whether <i>ADAMTS14</i> genetic variants play a role in hepatocellular carcinoma (HCC) susceptibility remains unknown.</p><p>Methodology/Principal findings</p><p>Four non-synonymous single-nucleotide polymorphisms (nsSNPs) of the <i>ADAMTS14</i> gene were examined from 680 controls and 340 patients with HCC. Among 141 HCC patients with smoking behaviour, we found significant associations of the rs12774070 (CC+AA vs CC) and rs61573157 (CT+TT vs CC) variants with a clinical stage of HCC (OR: 2.500 and 2.767; 95% CI: 1.148–5.446 and 1.096–6.483; <i>P</i> = 0.019 and 0.026, respectively) and tumour size (OR: 2.387 and 2.659; 95% CI: 1.098–5.188 and 1.055–6.704; <i>P</i> = 0.026 and 0.034, respectively), but not with lymph node metastasis or other clinical statuses. Moreover, an additional integrated <i>in silico</i> analysis proposed that rs12774070 and rs61573157 affected essential post-translation <i>O</i>-glycosylation site within the 3^rd thrombospondin type 1 repeat and a novel proline-rich region embedded within the C-terminal extension, respectively.</p><p>Conclusions</p><p>Taken together, our results suggest an involvement of <i>ADAMTS14</i> SNP rs12774070 and rs61573157 in the liver tumorigenesis and implicate the <i>ADAMTS14</i> gene polymorphism as a predict factor during the progression of HCC.</p></div