Computational Design of a Single Heater Convective Polymerase Chain Reaction for Point-of-Care

Recently, researchers have started working to develop polymerase chain reaction (PCR) devices as a means for point-of-care (POC) applications. Among the requirements are portability, affordability, and performing reliably and quickly. Proposed by the present study is a process to design a convective-PCR (CPCR) device with only a single heater. It is assumed that such a design developed using microfluidics and capillary tube should help make a CPCR to be portable and more economical for POC use. One of the challenges is to achieve steadily the prerequisite three temperature zones with a single heater. It is demonstrated that this can be done with the present methodology. The underlying physics of the convection driving the CPCR function is mathematically modeled, then verified by our experimental results. In search of better designs, the following parameters that affect the CPCR performance are considered: the heater's height, and the diameter, the height, and the wall thickness of the capillary tube. A large design space consisting of design candidates is defined by combining the values within the range of each of these parameters. The results of the corresponding design cases are obtained from our mathematical model, and the performance of each case is evaluated by their deoxyribonucleic acid (DNA) doubling time. The two best CPCR performing reactors are selected and discussed. It is, therefore, demonstrated that the present methodology is capable of enhancing the CPCR reactor performance with a single heater.

[1]  Angelika Niemz,et al.  Point-of-care nucleic acid testing for infectious diseases. , 2011, Trends in biotechnology.

[2]  David Erickson,et al.  Numerical simulations of a low power microchannel thermal cycling reactor , 2002 .

[3]  Oktay Baysal,et al.  Aerodynamic Shape Optimization: Methods and Applications , 1999 .

[4]  Ping-Hei Chen,et al.  Sensors and Actuators B: Chemical , 2022 .

[5]  Victor M Ugaz,et al.  PCR in a Rayleigh-Bénard convection cell. , 2002, Science.

[6]  Sabrina Conoci,et al.  PCR Technologies for Point of Care Testing: Progress and Perspectives. , 2017, ACS sensors.

[7]  Kevin D. Dorfman,et al.  Coupled flow and reaction during natural convection PCR , 2013 .

[8]  B. Gale,et al.  A disposable, continuous-flow polymerase chain reaction device: design, fabrication and evaluation , 2016, Biomedical Microdevices.

[9]  K. Vafai,et al.  Rapid microfluidic thermal cycler for polymerase chain reaction nucleic acid amplification , 2008 .

[10]  Andreas Manz,et al.  Handheld real-time PCR device. , 2016, Lab on a chip.

[11]  Ping-Hei Chen,et al.  Development of Capillary Loop Convective Polymerase Chain Reaction Platform with Real-Time Fluorescence Detection , 2017 .

[12]  Kevin D. Dorfman,et al.  Polymerase chain reaction in natural convection systems : A convection-diffusion-reaction model , 2005 .

[13]  S. Churchill,et al.  Correlating equations for laminar and turbulent free convection from a vertical plate , 1975 .

[14]  Duli Yu,et al.  Real-time capillary convective PCR based on horizontal thermal convection , 2019, Microfluidics and Nanofluidics.

[15]  Victor M Ugaz,et al.  A pocket-sized convective PCR thermocycler. , 2007, Angewandte Chemie.

[16]  Shizhi Qian,et al.  A Low-Cost and Fast Real-Time PCR System Based on Capillary Convection , 2017, SLAS technology.

[17]  Dieter Braun,et al.  Exponential DNA replication by laminar convection. , 2003, Physical review letters.

[18]  Carl T Wittwer,et al.  Extreme PCR: efficient and specific DNA amplification in 15-60 seconds. , 2015, Clinical chemistry.

[19]  Ping-Hei Chen,et al.  Rapid DNA amplification in a capillary tube by natural convection with a single isothermal heater. , 2011, BioTechniques.

[20]  O. Baysal,et al.  Performance Evaluation of a Micro Synthetic-Jet Actuator via Its Generated Vortices , 2009 .

[21]  Yingfu Li,et al.  Detection of DNA Amplicons of Polymerase Chain Reaction Using Litmus Test , 2017, Scientific Reports.

[22]  Y. Çengel.  Heat and Mass Transfer: Fundamentals and Applications , 2000 .

[23]  Ke Li,et al.  A smartphone-based point-of-care diagnosis of H1N1 with microfluidic convection PCR , 2017 .

[24]  Oktay Baysal,et al.  Performance of convective polymerase chain reaction by doubling time , 2019, International Journal of Heat and Mass Transfer.

[25]  J. El-Ali,et al.  Simulation and experimental validation of a SU-8 based PCR thermocycler chip with integrated heaters and temperature sensor , 2004 .

[26]  Richard Bruch,et al.  Multiplexed Point-of-Care Testing – xPOCT , 2017, Trends in biotechnology.

[27]  Jung Il Shu,et al.  Computational Analysis and Design Optimization of Convective PCR Devices , 2019 .

[28]  Chunsun Zhang,et al.  PCR microfluidic devices for DNA amplification. , 2006, Biotechnology advances.

[29]  B. Cooper,et al.  Multiplex PCR point of care testing versus routine, laboratory-based testing in the treatment of adults with respiratory tract infections: a quasi-randomised study assessing impact on length of stay and antimicrobial use , 2017, BMC Infectious Diseases.

[30]  Songlin Zhuang,et al.  The development of a portable buoyancy-driven PCR system and its evaluation by capillary electrophoresis , 2016 .