A low-cost and miniaturized potentiostat for sensing of biomolecular species such as TNF-α by electrochemical impedance spectroscopy.

Miniaturizing potentiostats, keeping their cost low and yet preserving full measurement characteristics (e.g. bandwidth, determination of capacitive/inductive contribution to sensor's impedance and parallel screening) is still an unresolved challenge in bioelectronics. In this work, the combination of simple analogue circuitry together with powerful microcontrollers and a digital filter implementation is presented as an alternative to complex and incomplete architectures reported in the literature. A low-cost acquisition electronic system fully integrated with a biosensors platform containing eight gold working microelectrodes and integrated reference and counter electrodes was developed and validated. The manufacturing cost of the prototype was kept below 300 USD. The performance of the proposed device was benchmarked against a commercial impedance analyzer through the electrochemical analysis of a highly sensitive biosensor for the detection of tumor necrosis factor α (TNF-α) within the randomly chosen range of 266pg/mL to 666ng/mL in physiological medium (PBS). A strong correlation between the outputs of both devices was found in a critical range of frequencies (1-10Hz), and several TNF-α cytokine concentrations were properly discriminated. These results are very promising for the development of low-cost, portable and miniaturized electrochemical systems for point-of-care and environmental diagnosis.

An Integrated Circuit for Chip-Based Analysis of Enzyme Kinetics and Metabolite Quantification.

We have created a novel chip-based diagnostic tools based upon quantification of metabolites using enzymes specific for their chemical conversion. Using this device we show for the first time that a solid-state circuit can be used to measure enzyme kinetics and calculate the Michaelis-Menten constant. Substrate concentration dependency of enzyme reaction rates is central to this aim. Ion-sensitive field effect transistors (ISFET) are excellent transducers for biosensing applications that are reliant upon enzyme assays, especially since they can be fabricated using mainstream microelectronics technology to ensure low unit cost, mass-manufacture, scaling to make many sensors and straightforward miniaturisation for use in point-of-care devices. Here, we describe an integrated ISFET array comprising 2(16) sensors. The device was fabricated with a complementary metal oxide semiconductor (CMOS) process. Unlike traditional CMOS ISFET sensors that use the Si3N4 passivation of the foundry for ion detection, the device reported here was processed with a layer of Ta2O5 that increased the detection sensitivity to 45 mV/pH unit at the sensor readout. The drift was reduced to 0.8 mV/hour with a linear pH response between pH 2-12. A high-speed instrumentation system capable of acquiring nearly 500 fps was developed to stream out the data. The device was then used to measure glucose concentration through the activity of hexokinase in the range of 0.05 mM-231 mM, encompassing glucose's physiological range in blood. Localised and temporal enzyme kinetics of hexokinase was studied in detail. These results present a roadmap towards a viable personal metabolome machine.