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.

Highlights

  • Novel developments in Point-of-Care and Lab-on-a-Chip devices are targeted at applications that require temperature control, especially nucleic acid amplification tests (NAAT)

  • We propose a temperature control solution based on self-regulating resistive heating that has a temperature control precision sufficient for loop-mediated isothermal nucleic acid amplification (LAMP), is cheap enough to be disposable and power-efficient enough to run from 2xAAA alkaline batteries

  • We demonstrated a self-regulating resistive heating solution for disposable LoC NAAT devices. 4 heating element samples (Fig 1D) were provided by Heatron Inc. with different temperature-dependent resistivity profiles (Table 4) that matched the lower and upper end of the targeted 60–63 ̊C temperature range

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Summary

Introduction

Novel developments in Point-of-Care and Lab-on-a-Chip devices are targeted at applications that require temperature control, especially nucleic acid amplification tests (NAAT). Isothermal NAATs require a single temperature range to be maintained in the reaction volume for the specified amplification time [1,2,3,4], making them more suitable for Lab-on-a-Chip applications than PCR, which requires thermal cycling. Non-instrumented LoC NAAT devices pose unique technical challenges resulting from space, power and cost constraints characteristic of the platform [5]. These constraints have made commercialization difficult in the past, limiting availability to the general public

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