Diagnostic Technologies

Non-instrumented nucleic acid amplification (NINA) platform


Project overview

NINA Illustration

Cut-away view of the reusable NINA device showing relative location of insulation, heat source, phase change material, and samples. Photo: PATH.

PATH lead development of technologies that facilitate electricity-free, instrument-free nucleic acid amplification. The development of a non-instrumented nucleic acid amplification (NINA) heating device using an exothermic chemical reaction and engineered phase-change material represents the first example of electricity-free nucleic acid amplification. In the NINA heater, we used the exothermic reaction to generate the heat necessary for the amplification reaction to take place. Coupling this reaction with engineered phase change material enables reproducible and tunable temperature control.

Project location

Worldwide

Dates of project

2010 – 2015 This page is an archived record of a project that has closed. If you are interested in more information about the NINA device, contact dxinfo@path.org

Partners

US Centers for Disease Control and Prevention

Funding sources

National Institutes of Health

Needs

NINA Thermal Image

Thermal imaging of the NINA device was used to assess heat losses and compare insulating materials. Photo: PATH.

Many infectious diseases that affect global health are most accurately diagnosed through nucleic acid amplification and detection. However, existing nucleic acid amplification tests (NAATs) have traditionally been too expensive and complex for most low-resource settings. The small numbers of centralized laboratories that exist in low-resource settings (LRS) tend to be in urban areas and primarily cater to the affluent. In contrast, health care facilities in rural areas commonly have only basic equipment, and health workers have limited training and little ability to maintain equipment and handle reagents. Unreliable electrical power and the difficulty of maintaining a diagnostic instrument powered by electricity create additional barriers to the use of NAATs at the point of care (POC). Additionally, battery-powered instruments cannot serve as reliable alternatives, as batteries have poor shelf lives, offer poor performance in extreme temperatures, can be prohibitively costly, and can easily be removed and used for other purposes. Despite the need small, portable, low-cost, instrument-free NAATs that can be used in LRS are not commercially available today.

There are many infectious diseases rampant in LRS where the lack of simple, instrument-free, nucleic acid based diagnostic tests is a critical barrier to timely diagnosis and treatment. These diseases include malaria, human immunodeficiency virus (HIV), tuberculosis, influenza, among others. HIV diagnosis is a good example of an infectious disease that could benefit from greater NAAT access at the POC in LRS.

Ideally, an HIV diagnostic test for such settings would be rapid, cost-effective, and capable of detecting recent or acute infections when the infected individual is at a much higher risk of transmitting the virus. In the case of infants born to HIV-positive mothers, diagnosis and antiretroviral therapy immediately after birth can significantly improve the outcome of the infected infant. Currently available HIV diagnostics either only detect the host’s immune response (after the acute phase) or use highly infrastructure-dependent technologies.


Goals

The goal of this project was to develop a POC diagnostic device that replaces traditional heating elements and control mechanisms with exothermic reactions and engineered phase change materials, obviating the need for electricity. This innovation will provide extremely low-cost, precisely controlled heat for isothermal NAAT processes in environments where electricity is not available or is unreliable. The device has the potential to enable the use of high accuracy NAATs at the POC. Although the NINA technology is viewed as a platform useful to detect many infectious diseases, the focus of the project was to improve detection of acute and infant HIV diagnosis.


Approach

The overall strategy of this project was to combine two complementary technologies under development at PATH and the US Centers for Disease Control and Prevention (CDC)—the NINA platform and an HIV loop-mediated isothermal amplification (LAMP) assay amenable for use in LRS.

PATH demonstrated the use of calcium oxide and a proprietary engineered phase change material to stabilize the temperature of an assay mixture within a narrow range suitable for LAMP. The CDC have developed a novel combination of lysis buffer, LAMP and fluorescently labeled primers to enable visual detection. The development of the prototype NINA device in conjunction with the CDC’s HIV LAMP assay represents the first example of using an exothermic chemical reaction and engineered phase-change material in an NAAT.


Status

The PATH-CDC collaboration has demonstrated detection of HIV-1 RNA in human blood specimens using the NINA heater to thermally stabilize reaction mixtures within the narrow temperature ranges required for a variety of isothermal amplification strategies (58°–60°C, 60°–63°C, 63°–65°C). NINA heater prototypes have also been used to demonstrate proof of principle via LAMP DNA amplification from the following pathogens: Plasmodium falciparum (malaria), HIV-1 (DNA and RNA), Ralstonia solanacearum (an agricultural pathogen), Salmonella, and Mycobacterium ulcerans (Buruli ulcer).

This page is an archived record of a closed project. If you are interested in more information about the NINA device, contact dxinfo@path.org


 

Resources

Publications

View our NINA publications on NCBI