Synthetic biology enabled wearable biosensors for non-invasive biomarker monitoring using sweat

Abstract

Monitoring biomarkers is key to understanding human health and diagnosing disease. Frequently this requires blood samples to be taken for subsequent testing. It has disadvantages including pain and infection risk to the individual being sampled and a significant time lag before the results are known.

Most blood-based monitoring tests require samples to be taken in a healthcare setting by trained personnel and the sample sent to a laboratory for analysis. This limits access to biomarker monitoring.

Using alternative biofluids such as saliva and urine still requires active sample production so sampling can be inconvenient for individuals. Sweat has many potential advantages for monitoring biomarkers as it allows for non-invasive sampling, which can be carried out passively, and sweat contains a number of different potential markers of health and physiological status. As a result sweat has become a key area of focus in developing new monitoring devices, particularly in the use of wearable devices that allow passive monitoring. Research in this area has used electrochemical sensors for detection of biomarkers, but electrochemical sensors have potential disadvantages in terms of cost and how the sensing is impacted by temperature, humidity, movement and other variables. Synthetic biology has developed a wide range of tools capable of generating biosensors with highly tailorable characteristics, which are potentially suitable for monitoring biomarkers whilst being more capable of withstanding changes to their environment. In this project multiple biosensors using different approaches of whole cell biosensors, aptamer-based sensors and fluorescent protein-binding based sensors have been developed and shown to be capable of detecting biomarkers for lactate, potassium, tryptophan, histamine, testosterone and cortisol, all of which are thought to show information on physiological state. To test the suitability of whole cell sense and respond genetic circuits, a novel tryptophan biosensor was developed as part of the project. Engineered proteins containing circularly permuted GFP were also developed to generate biosensors for cortisol, testosterone and histamine. These sensors have been shown to respond to target analytes in sweat at the required range. These sensors have also been encapsulated into a hydrogel material to show it is possible to combine these sensors into a wearable device which would be suitable for passive monitoring, thus demonstrating the suitability of biosensors to generate a new approach to biomarker monitoring.