Harnessing Chaotic Flow Effects in Microscale Natural Convection to Achieve Accelerated Biochemistry

The lack of rapid, affordable, and easy to use medical diagnostic technologies is a critical issue confronting global public health. A major challenge to these efforts lies in the design of instrumentation used to perform a key step in the analysis. This step, the polymerase chain reaction (PCR), involves a sequence of thermally activated biochemical processes that selectively replicate well-defined sub regions within a longer DNA strand. Although PCR is generally considered to be a mature technology from a biochemical standpoint, many limitations are still imposed by the highly inefficient design of conventional PCR thermocycling hardware that is slow, expensive, and consumes considerable electrical power to repeatedly heat and cool the reagent mixture. Here we describe an alternative thermocycling approach that has the potential to addresses these needs by harnessing thermally driven natural convection to perform rapid DNA amplification via the PCR. A buoyancy driven instability is induced within a confined volume of fluid by imposing a spatial temperature gradient. Under the right conditions (fluid properties, geometry, temperature gradient, etc.) a stable circulatory flow pattern can be established that will repeatedly transport PCR reagents through temperature zones associated with each stage of the reaction. The inherently simple design (similar in principle to a lava lamp) and minimal electrical power consumption make this approach well-suited for use in portable applications. We also describe our computational and experimental studies of the flow fields established within convective thermocycling reactors, revealing a rich complexity not found in most steady laminar flows. These complexities arise because, under the thermal conditions associated with PCR, the nature of the buoyancy driven instabilities that initiate and sustain motion make it necessary to operate in a transition regime associated with the onset of convective turbulence. These unique characteristics can be harnessed to guide the design of new devices capable of generating optimal conditions for ultra-rapid PCR replication.