Thermal Analysis of a Disposable, Instrument-Free DNA Amplification Lab-on-a-Chip Platform

Abstract

Novel second-generation rapid diagnostics based on nucleic acid amplification tests (NAAT) offer performance metrics on par with clinical laboratories in detecting infectious diseases at the point of care. The diagnostic assay is typically performed within a Lab-on-a-Chip (LoC) component with integrated temperature regulation. However, constraints on device dimensions, cost and power supply inherent with the device format apply to temperature regulation as well. Thermal analysis on simplified thermal models for the device can help overcome these barriers by speeding up thermal optimization. In this work, we perform experimental thermal analysis on the simplified thermal model for our instrument-free, single-use LoC NAAT platform. The system is evaluated further by finite element modelling. Steady-state as well as transient thermal analysis are performed to evaluate the performance of a self-regulating polymer resin heating element in the proposed device geometry. Reaction volumes in the target temperature range of the amplification reaction are estimated in the simulated model to assess compliance with assay requirements. Using the proposed methodology, we demonstrated our NAAT device concept capable of performing loop-mediated isothermal amplification in the 20–25 °C ambient temperature range with 32 min total assay time.

Can 3D Printing Bring Droplet Microfluidics to Every Lab?—A Systematic Review

“…However, they can also be used to study electromagnetic or thermal effects. For instance, they can be used to analyze heat distribution under various operating conditions in microchannels where measurements would be difficult in situ [ 143 , 144 ]. Furthermore, they can be used to analyze electromagnetic fields and optimize electrode or magnet placement [ 100 , 145 ].…”

From Lab on a Chip to Point of Care Devices: The Role of Open Source Microcontrollers

“…For measuring temperatures lower than 130 Celsius, the ubiquitously available analog temperature sensor TMP36 can be used [ 32 , 33 ]. For measurement of higher temperatures, up to 1000 Celsius, a suitable thermocouple and break-out board containing temperature sensing electronics can be selected [ 31 , 34 ]. For building of a thermocycler such as a polymerase chain reaction (PCR) machine, it is informative to look at the work of Chai, a company founded by Josh Perfetto and Jessie Ho at where they built up a PCR thermocycler based on an Arduino Uno.…”

Development of a Low-Cost, Wireless Smart Thermostat for Isothermal DNA Amplification in Lab-On-A-Chip Devices

“…Self-regulating resistive heating elements are an interesting novel solution to integrated temperature control as they require no thermostat [21,22,23,24,25]. However, due to the open-loop nature of the PTCR (positive temperature coefficient of resistance) effect used for control, they require extensive optimization to the particular NAAT protocol and ambient temperature conditions they are used in [21]. Noncontact electrical heating solutions include induction and microwave heating [26], but are impractical for portable applications.…”

“…In previous works, we demonstrated the integration of commercially available electrical heating elements into isothermal LoC NAAT devices [46,47,48,49,50]. Furthermore, we demonstrated the application of a self-regulating PTCR polymer-resin heating element in a LoC NAAT device, including thermal analysis [21,51] and proof-of-concept LAMP tests [22]. Previously we focused exclusively on low-cost, integrated heating solutions for use specifically in single-use LoC devices and primarily on the LAMP assay.…”

“…Simulation via finite element modelling is used to verify that the reaction volume is in range in steady state at each temperature target, as well as to define the best steady-state error achievable by the system. The thermal evaluation methodology used in this paper was demonstrated in our previous works [21,52].…”