Detection of specific DNA sequences in biofluids

Presently available biosensors are based on a labelling technique where DNA molecules of the biosample under test are firstly tagged by fluorescent labels so that their immobilization with a given probe can be visualized. However, the labelling step is costly, time consuming, and can drastically change the binding properties of the molecules. This restricts these techniques to centralized services in hospitals.

Nanonets2Sense aims at developing the 3D integration of silicon nanonets into nanonet-based field-effect transistors, their integration above conveniently designed readout circuit, and their functionalization with some DNA model sequences. This provides a label-free detection, based on the monitoring of the modification of the electrical properties of nanonets, in response to DNA probe/target recognition between the DNA sequences present in the biofluid sample to be analysed and some DNA probe sequences grafted beforehand on the nanonet. This would afford low-cost, small size, portable tools available at the point-of-care. This integrated approach allows the sequential testing of full arrays of sensors, making multiplex detection achievable, with increased reliability. It would for instance be possible to average the response of several pixels functionalized with the same probe, to use different probes that could detect several DNA sequences typical of the same disease, and to keep a reference with some pixels free of any probe or functionalized with non-complementary probes.

Many medical applications can be envisioned, for instance in the field of pharmacogenetics (e. g. to be aware of the genetic characteristics which can influence patient reaction to a medical treatment), or in therapy monitoring (e.g. to monitor the amount of circulating micro-RNA sequences which are released in blood during treatment by dying cancerous tumours).

Detection of acetone in breath:

The other aim of Nanonets2Sense is to explore the potential of nanonets, here made of ZnO, to detect gases such as acetone in the exhaled breath and provide the information on a handheld terminal such as a cell phone. Heating is necessary to activate the surface interactions which are at the core of the detection principle. The key there is to demonstrate the integration of such ZnO nanonets on the micro hotplates which are used to localize the heating exactly below the sensing material.

Breath tests are becoming popular as non-invasive methods of disease diagnoses, due to their quick results and ease of use. Exhaled breath consists of many different molecular species, and some of them are typical of diseases. With diabetes, acetone content increases significantly in breath as fatty acids are metabolized for energy during periods of glucose deficiency, and it is thus a useful biomarker of type I diabetes.

Indeed, with 60 million people diagnosed with diabetes and about 20% of 742 million EU population considered to be obese, potential demand for health and wellbeing acetone sensors can be estimated to be 148 million. Globally, the World Health Organization reports that in 2014, 9% of the population was estimated to be diabetic, with 13% considered to be obese, thus, globally this figure can be estimated to increase to more than 1.2 billion. Given the fact that annual global new smartphone shipment amounts to 380 million, and assuming 20% of the new phones incorporate the acetone sensors, this means a potential market is worth about 76 million units. With wearable and portable devices, this market opportunity is likely to be significantly larger.