Development of Temperature Control Solutions for Non-Instrumented Nucleic Acid Amplification Tests (NINAAT)

Abstract

Non-instrumented nucleic acid amplification tests (NINAAT) are a novel paradigm in portable molecular diagnostics. They offer the high detection accuracy characteristic of nucleic acid amplification tests (NAAT) in a self-contained device, without the need for any external instrumentation. These Point-of-Care tests typically employ a Lab-on-a-Chip for liquid handling functionality, and perform isothermal nucleic acid amplification protocols that require low power but high accuracy temperature control in a single well-defined temperature range. We propose temperature control solutions based on commercially available heating elements capable of meeting these challenges, as well as demonstrate the process by which such elements can be fitted to a NINAAT system. Self-regulated and thermostat-controlled resistive heating elements were evaluated through experimental characterization as well as thermal analysis using the finite element method (FEM). We demonstrate that the proposed solutions can support various NAAT protocols, as well as demonstrate an optimal solution for the loop-mediated isothermal amplification (LAMP) protocol. Furthermore, we present an Arduino-compatible open-source thermostat developed for NINAAT applications.

Simple Approaches to Minimally-Instrumented, Microfluidic-Based Point-of-Care Nucleic Acid Amplification Tests

“…The availability or reliability of electrical grid power can be an issue in many parts of the developing world, and there is an interest in minimally-instrumented POC formats, particularly battery-operated diagnostics devices that can operate free of utilities and generators, or even non-electrical devices that do not need batteries [ 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ]. The primary electrical power consumption of a molecular diagnostics device is for controlled incubation of the amplification reaction.…”

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

“…For temperature controlling and measurement, the Arduino Uno is widely used, for instance in references [ 27 , 28 , 29 , 30 , 31 , 32 ]. For measuring temperatures lower than 130 Celsius, the ubiquitously available analog temperature sensor TMP36 can be used [ 32 , 33 ].…”

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

“…15 Although chemical heaters do not require batteries or external power supplies, they typically rely on highly variable exothermic reactions such as magnesium iron alloy (MgFe) and saline cartridges which are single-use and are difficult to control without a phase change material (PCM) chamber to buffer the sample temperatures. 10,[16][17][18] Current PCB-based heaters, while effective, require long copper traces which result in slow rampups to the target temperature and excess heat and power consumption. 7 In Hwang et al, sample overheating and control of the working voltage for each heating stage of a polymerase chain reaction (PCR) to detect Chlamydia trachomatis remained problematic even after reducing the size of the heating pattern and utilizing a complex electronics system to perform the thermocycling.…”