Micro-Scale Transport Processes for Advanced Healthcare and Point of Care Diagnostics

Recent outbreaks like Zika and Ebola highlights the challenges associated with pathogen diagnostics in the developing world. With the outbreak in Africa, and isolated cases on other continents, the need for an affordable, rapid and portable diagnostic solution has been repeatedly stressed and is one of the most critical issues confronting global health. Unfortunately, the current conventional PCR instrumentation needed to perform gold standard DNA-based diagnostic tests is bulky, slow, and expensive, making it unsuitable for resource-limited settings in developing countries where dedicated laboratory facilities are not available. Advances in micro-fluidics and smartphone based technology has paved way for novel implementations of traditional molecular diagnostic techniques. We present a series of advances in molecular diagnostic techniques by harnessing convective flow to actuate biochemical reactions. INTRODUCTION Recently, it has been shown that convective flow fields can be harnessed to perform PCR. Our research led us to investigate the underlying physics of these thermally driven micro-scale Rayleigh-Bénard convective flows. This new understanding revealed how a subset of these flow fields exhibit chaotic advection that greatly accelerate temperature driven biochemical reactions such as PCR [1-6]. Since its first introduction a little over a decade ago, convective thermo-cycling has remained an intriguing avenue to enable rapid PCR. However, a crucial roadblock to practical implementation of this approach has been the inherent interdependence between the internal flow field and the reactor geometry (expressed in terms of the height, h, and diameter, d, of a cylindrically shaped configuration). The spatial temperature gradient established between the top (cool) and bottom (hot) surfaces of the reactor not only actuates the denaturing, annealing, and extension steps necessary to perform the PCR, it also supplies the driving force to physically transport reagents between these reaction zones. It has previously been assumed that this interplay implies a need to custom design reactor geometries to match the individual thermal requirements of each PCR assay to be performed (e.g., when different primers with different annealing temperatures are employed), and that robustness is constrained by a need to maintain a specific orientation with respect to the gravitational driving force. Figure 1: Real time fluorescent detection of convective PCR products via SYBR-PCR chemistry. A blue light source illuminates the convective PCR reactor and the images of the reactor top are taken with smart-phone camera which are subsequently analyzed with a built in image analysis app called PCRtoGo. . CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/113787 doi: bioRxiv preprint first posted online Mar. 5, 2017;