An Integrated Polymer Based Polymerase Chain Reaction And Capillary Electrophoresis System For Genetic Diagnosis

Micro-Total-Analysis-Systems (µTAS) for genetic diagnosis have a great potential to revolutionize the future of health care. However the lack of µTAS, which is fully integrated, mass-producible and application oriented, has delayed µTAS development in real life application. In this work, I developed designs, protocols and supporting infrastructures for a polymer-based, fully integrable genetic diagnosis system capable of the Polymerase Chain Reaction (PCR) and Capillary Electrophoresis (CE). Each individual module could be integrated through a novel valve/pumping design and is fully capable of hand-free operation. These modules have been demonstrated to have a separation similar to our previous generation glass-based chips, which have previously proved the capability of genetic diagnosis. The integrated PCR module has demonstrated the concept of a CMOS compatible PCR system that is capable of mass-production. These discrete PCR modules are rapid prototypes. Using laser-based and milling machine-based rapid prototyping methods, the fabrication processes and module designs were developed. During this, the designs were studied through simulations and back-of-the-envelope (BOE) calculations. At the time of writing, the valving, PCR and CE modules have been successfully tested (with publications in print, in press and underway). In addition, a valving and CE combination has also been successfully demonstrated for a restriction fragment length polymorphism (RFLP) diagnostic and submitted for publication. All of these designs were intended to be developed in a manner that could be implemented in a PMMA chip, or on a future CMOS chip for greater cost reduction. This work has developed some of the key technologies for PCR-CE in a way that is scalable to such a CMOS system, notably with valves that can be used in a hybrid PMMA/CMOS system, and in testing a silicon based and robust temperature control system that could be implemented on CMOS

Spatial-temporal pattern and influencing factors of tourism ecological security in Huangshan City

It is of important theoretical and practical value to scientifically evaluate tourism ecological security for the sustainable development of tourist cities. The study focuses on the “characteristics of the impact factors on tourism ecological security at different levels” of tourism ecological security that have been neglected in the previous literature. From the perspective of Compound Ecological systems theory, we built an evaluation index system for tourism ecological security in Huangshan City based on the Pressure-State-Impact-Economic-Environmental-Social (PSR-EES) model and used a combination of the entropy weight TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution) method, traditional and spatial Markov chains, and panel quantile regression to analyze and characterize the spatial-temporal dynamics of security levels and driving factors. The results showed that (1) the level of tourism ecological security of the districts and counties in Huangshan City improved rapidly, but the difference was expanding. The level of tourism ecological security in the four counties was generally higher than that in the three districts. (2) In terms of the spatial-temporal dynamic evolutionary characteristics, the transfer of tourism ecological security in Huangshan City has its characteristics of stability and path dependence. Type transfers usually occur between adjacent levels. The lower the level of tourism ecological security, the higher the probability of upward transfer. A neighborhood background plays an important role in the process by which a higher neighborhood rank increases the probability of upward transfer. (3) Regarding the driving factors, environmental pollution and economic development have a negative inhibitory effect on tourism ecological security, and the negative effect decreases as the level of TES improves. The top three positive effects were government intervention and educational levels. The degree of regional greening and government intervention had greater positive marginal effects on lower-level areas. In contrast, tourism development, educational level, and labor input had greater positive marginal effects on areas with higher TES levels

Polymeric rapid prototyping for inexpensive and portable medical diagnostics

Tianchi Ma, Victoria Northrup, Andrew O. Fung, D. Moira Glerum, Christopher J. Backhouse, "Polymeric rapid prototyping for inexpensive and portable medical diagnostics", Proc. SPIE 8412, Photonics North 2012, 84120B (24 October 2012); doi: 10.1117/12.2001470. Copyright 2012, Society of Photo Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited. https://doi.org/10.1117/12.2001470The advent of inexpensive CO2 laser systems has led to a wide range of demonstrations of microfabricated lab on chip systems built of acrylic. However, there has been little application of these systems to building microfluidics for DNA analysis. In this work we explore the use of CO2 laser systems for building microfluidics for DNA analysis and relate the artifacts of the fabrication technology to the performance of the system. We show that surface roughness that leads to significant constrictions in the separation channel provides an upper limit of the size of DNA that can be analysed. Below that upper limit, the resolution of the chip is strongly affected by the degree to which the separation channel is exposed to redeposited by-products of the ablation process. We show that by controlling these effects we are reliably able to discern two types of PCR product as a test representative of a real application. By being able to do this is in microfluidic devices the size of a postage stamp we have shown that we can now use CO2 laser systems for the development of extremely inexpensive diagnostic systems using a rapid prototyping approach.Natural Sciences and Engineering Research Council of CanadaTeledyne-DALS

Robust thermal control for CMOS-based lab-on-chip systems

The need for precise temperature control at small scales has provided a formidable challenge to the lab-on-chip community. It requires, at once, good thermal conductivity for high speed operation, good thermal isolation for low power consumption and the ability to have small (mm-scale) thermally independent regions on the same substrate. Most importantly, and, in addition to these conflicting requirements, there is a need to accurately measure the temperature of the active region without the need for device-to-device calibrations. We have developed and tested a design that enables thermal control of lab-on-chip devices atop silicon substrates in a way that could be integrated with the standard methods of mass-manufacture used in the electronics industry (i.e. CMOS). This is a significant step towards a single-chip lab-on-chip solution, one in which the microfluidics, high voltage electronics, optoelectronics, instrumentation electronics, and the world-chip interface are all integrated on a single substrate with multiple, independent, thermally-controlled regions based on active heating and passive cooling.Natural Sciences and Engineering Research Canada (NSERC)Teledyne-DALSA Semiconducto

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO