Development of Aptamer Functionalized ZnO Micro-ring resonators for BioSensing

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The aim of this PhD project is to develop a new biological sensing platform that will combine optical and electrical detection of a wide range of potential diseases, pathogens and toxins into a compact real time device capable of carrying out point of care diagnosis. A micro ring resonator (MRR) is a refractive index-based sensor. In a ring resonator light propagates in the form of circulating waveguide modes, which are a result of the total internal reflection of the light along the curved boundary of the ring between high and low refractive index materials. The light is coupled into the ring via an adjacent linear waveguide located within a few hundred nanometers. The circulating waves form a constructive interference pattern when the wavelength are divisors of the ring circumference. These are the so-called resonance frequencies of the ring resonator. These optical modes are sensitive to the evanescent field surrounding the waveguide, hence a bio-molecular binding event will cause a change in the resonance frequency. The change in the field is larger the closer the target protein is to the actual resonator. Recently short single stranded DNA strands, so called aptamers, have been drawing attention as the potential replacement of antibodies in sensor devices. The advantage of aptamers is that they are smaller than antibodies and hence bring the target proteins much closer to the sensing components, which results in a potential increase in the response. The potential for these systems is in the detection of proteins, both for infectious diseases and food toxins, with the possibility to achieve multi-channel sensors by utilizing arrays of MRRs. The project will also look to utilize aptamer functionalized ZnO to realize Field Effect Transistors (FETs) that can operate as electrical based bio sensor. The aptamer-FET based detector has a high sensitivity; a small perturbation in charge distribution near the channel will result in a marked change in the current, an order of magnitude difference is expected when directly comparing an aptamer FET with an antibody FET. In addition, the device can have high selectivity, enhanced by the use of multiple aptamer-FETs in an array, each probing for a different protein. As a result it will be possible to determine the protein fingerprint in any liquid sample. The detector can be operated at a low supply voltage of typically 3 V. This means that the translational potential of this work is most relevant to regions where laboratory infrastructure is scarce, technical ability is limited and time is short. This could mean UK primary care, where there is huge pressure for a quick diagnosis, improved accuracy of infection diagnosis and improved antibiotic stewardship, but also in a developing world setting. The final stage of the project will seek to combine these 2 sensors into one where ZnO is used as both the channel material in the aptamer-FET and the waveguide in the aptamer-MRR, allowing the combination of both the optical and electrical sensing device in a single sensor occupying the same space. The advantage of this is that the two techniques will provide a control of each other without the need of additional experiments or multiple sensors on one device. Although this approach will be applicable for a wide variety of proteins, the initial work will focus on one important example: aflatoxin B1. Aflatoxins are one of the most dangerous of the mycotoxins and they are the secondary metabolic products of the fungal genus Aspergillus. The most toxic compound is aflatoxin B1, which affects not only human, but also other primates, mammals, fish, birds and rodents. It mainly affects the liver function. In addition aflatoxin B1 is considered to be the most toxic natural hepatocarcinogen. As a result many countries have limits to the amount of aflatoxin that can be present in foodstuff, for example the European Union has set the limit at 2 ug kg-1 for aflatoxin B1.