Towards solid-state biosensors for evidence-based management of febrile illness

Fever is a major reason for seeking medical care globally. It is the most prevalent symptom of infection, whether viral, bacterial, parasitic or fungal. The unspecific nature of fever makes it particularly challenging to identify a specific etiology, especially in low- and middle-income countries where diagnostic resources are scarce or absent. Incorrect or delayed diagnosis of acute fever is causing many preventable deaths and fuels the global rise in antimicrobial resistance. There is an urgent need for a simple to use, inexpensive and rapid diagnostic testing technology which can detect a multiplexed panel of biomarkers relevant to diagnosing and managing febrile illness. In this thesis, we provide a first approach based on solid-state microfabricated electrochemical sensors that are well suited for mass-manufacturing at low costs. We first report about a pH sensor based on a single layer of conductive TiN, which greatly simplifies pH sensor fabrication. Then, we demonstrate the sensing of dissolved oxygen using a nanotitration approach which does not require an oxygen-permeable membrane. We further demonstrate that our approach yields additional information on the buffer capacity of a solution. Next, we introduce the idea of redox-active nanopores for sensing proteins. We show that the redox-cycling current in such pores exhibits a weaker dependence on the pore diameter than the ionic current used in traditional nanopore analytics. This is advantageous for an increased signal-to-noise ratio and ultimately for improving the accessibility of nanopore analytics on proteins. Finally, we discuss how further development of these sensors could enable the detection of hypoxemia, anemia and various host protein markers to differentiate between bacterial and viral infections and significantly reduce antibiotics prescription among febrile patients while improving treatment outcome.