#Poc molecular diagnostics portable#

Inspired by this model, we aimed to leverage this established diagnostic infrastructure as a universal interface for emerging diagnostic toolsets from the field of synthetic biology. The widespread adoption of glucose monitors has resulted in a global network of device manufacturing and consumable distribution, as well as broad acceptance by patients and clinicians. These devices are based on a glucose-dependent electrochemical signal generated by an enzyme, such as glucose oxidase, in their test strips 29.

#Poc molecular diagnostics portable#

As one of the most widely used PoC monitoring devices, it has significantly improved the lives of millions of people with diabetes by enabling the portable quantification, and therefore personal management, of blood sugar levels. Recognizing the importance of this challenge, we identified the blood glucose meter as a potential solution. While gene circuit-based sensors provide a promising solution, they need to be paired with companion technologies to be used outside of the laboratory. As demonstrated by the SARS-CoV-2 outbreak, access to diagnostics is critical and shortages can be a significant bottleneck to containment, leading to restrictions in movement and normal life 28. These advances are bringing real-time surveillance of outbreaks and low-cost tools for accessible global health closer to reality. This is especially relevant for PoC diagnostics where the principles of rational design from synthetic biology are enabling the rapid and low-cost development of sensors for pathogens and small molecules. One of the most exciting aspects of these efforts is the potential to improve access to health care. Using the cell-free enzymatic machinery of transcription and translation, these systems allow for gene circuits to operate as they do inside living cells 17, 20.Įfforts to develop cell-free technologies have been particularly successful for point-of-care (PoC) diagnostics, environmental sensing 4, 17, 21, 22, 23, 24, on-demand manufacturing of protein-based therapeutics 9, 18, 19, 25 and education 26, 27. This has led to efforts to move synthetic biology out of the cell using cell-free protein expression systems which vastly accelerates the design-test cycle 14, 15, 16 and enables these biotechnologies to be housed in a biosafe format that can be freeze-dried for distribution and use without refrigeration 4, 9, 17, 18, 19. Work to date in the field has largely relied on encoding functions into cells, which can take months or years to reach a final product 13. This trend toward practical implementation is setting the stage for biology to address unmet needs in health and food security 4, 5, 6, 7, 8, 9, green manufacturing and energy 10, amongst many others 11, 12. The field of synthetic biology, now on the verge of its third decade, is emerging from its formative tool-building phase into one that is application focused 1, 2, 3. Using this glucose-meter interface, we demonstrate the detection of a small-molecule analyte sample-to-result diagnostics for typhoid, paratyphoid A/B and show the potential for pandemic response with nucleic acid sensors for SARS-CoV-2. We show the development of new glucogenic reporter systems, multiplexed reporter outputs and detection of nucleic acid targets down to the low attomolar range. We describe a molecular translator that can convert the activation of conventional gene circuit-based sensors into a glucose output that can be read by off-the-shelf glucose meters. Here, we leverage the glucose meter, one of the most widely available point-of-care sensing devices, to serve as a universal reader for these decentralized diagnostics. However, it remains a challenge to deliver this sensing capacity into the hands of users in a practical manner. Recent advances in cell-free synthetic biology have given rise to gene circuit-based sensors with the potential to provide decentralized and low-cost molecular diagnostics. Nature Communications volume 12, Article number: 724 ( 2021) A glucose meter interface for point-of-care gene circuit-based diagnostics