Integrated self-regulating resistive heating for isothermal nucleic acid amplification tests (NAAT) in Lab-on-a-Chip (LoC) devices

Abstract

Isothermal nucleic acid amplification tests (NAAT) in a Lab-on-a-Chip (LoC) format promise to bring high-accuracy, non-instrumented rapid tests to the point of care. Reliable rapid tests for infectious diseases allow for early diagnosis and treatment, which in turn enables better containment of potential outbreaks and fewer complications. A critical component to LoC NAATs is the heating element, as all NAAT protocols require incubation at elevated temperatures. We propose a cheap, integrated, self-regulating resistive heating solution that uses 2xAAA alkaline batteries as the power source, can maintain temperatures in the 60–63°C range for at least 25 minutes, and reaches the target range from room temperature in 5 minutes. 4 heating element samples with different electrical characteristics were evaluated in a thermal mock-up for a LoC NAAT device. An optimal heating element candidate was chosen based on temperature profiling. The optimal candidate was further evaluated by thermal modelling via finite element analysis of heat transfer and demonstrated suitable for isothermal nucleic acid amplification.

Versatile printed microheaters to enable low-power thermal control in paper diagnostics

“…The "self-regulating" heaters had average initial resistances of 0.8 Ohms and average steady-state resistance (heatedup) of 13.6 Ohms which ultimately required 3 V of DC power to reach 61.5-64°C. 47 In our work, a single 5.5 Ohm microheater was heated for 15 minutes for ten trials and produced heat curves with no significant difference between heating trials and standard deviations between 4.3 and 4.9 within the trials (Fig. 4E, Tables S4 and S5 †).…”

“…Because there is no resistance drift for these resistors, we can easily maintain both temperature and power settings. Pardy et al evaluated commercial prototype elements and maintained temperature between 60-63°C for 25 minutes 47 featuring heating elements that increase in resistance with temperature. They claimed this resistance drift made the heaters self-regulating.…”

“…Our use of a single rechargeable NiMH AA battery is the lowest power and most sustainable solution for high temperature incubations to-date. Tang et al 54 and Pardy et al 47 both used two AAA alkaline batteries to produce their 3 V potential necessary for heating their LAMP reactions to 65°C. The Yager lab powered their MAD NAAT assembly containing multiple electronic components including a custom PCB heater with two AA batteries.…”

“…Pardy et al discussed the positive attributes of alkaline batteries including their low price, relatively small size and good energy density, however NiMH batteries also have these qualities and are known to provide a better voltage plateau (meaning more stable discharge over time) than rechargeable alkaline batteries resulting in more consistent heating for a longer time period. 47,48 Alkaline and NiMH batteries are both considered non-hazardous waste and can be recycled if recycling is available in the region. By reducing the power by more than half (from 3 V to 1.2 V), we also enable a greater ability to incorporate these microheaters into cheap and portable cell phone powered platforms for multi-temperature and sequential heating, which was successful.…”

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

“…We compared the performance of a commercially available self-regulating heating element to a thermostat-regulated etched foil heating element in LoC NAAT prototypes and concluded that self-regulating heating was the favorable option for disposable instrument-free LoC NAAT devices [ 33 ]. Furthermore, we demonstrated a self-regulating heater integrated with a LoC prototype system, with which we performed loop-mediated isothermal amplification (LAMP) in the 20–25 °C room temperature range [ 34 ]. In this work, we introduce the concept device of our instrument-free LoC NAAT platform and perform thermal analysis on it to verify that it is capable of supporting LAMP in the expected end-user environment.…”