Label-free biosensor arrays using open circuit potential measurements

Electrochemical sensors can be miniaturised more readily than optical sensors and are suitable for use with portable instrumentation by minimally trained clinical personnel. A real-time measuring system could provide detailed understanding of complex biological systems. Label-free high throughput analysis methods allowing protein/DNA quantitative detection is highly desirable. In particular field-effect devices are promising candidates for the development of inexpensive microarrays associated with portable instrumentation. These stable semiconductor devices measure variations in the open circuit potential (OCP) that occur at the metal gate interface when the charge density and distribution of the immobilised biolayer changes upon interaction with a bioconjugate.

We here present a multi-channel biosensor using direct multiplexed OCP variation measurements. The OCP was measured in real time using an ultra-low input bias current instrumentation amplifier providing an accurate differential measurement of voltage. An array of high resolution, multi-channel, simultaneous-sampling, Sigma-Delta ADCs convert the OCP differential measurements from analog to digital. Thus, the microcontroller could use the measurement data from an array of sensor inputs, which are at very high accuracy.
The microcontroller provide overall controls and monitoring through its peripherals. A higher level of controls and monitoring is done through LabVIEW, or own written program. Automated process could be pre-programmed. USB or TCP/UDP protocols communication is used to transfer real-time measurement data and controls between the microcontroller and PC. A fully automated and accurate measurement system is hence achieved with direct computer interface for logging and analysis of the data.
The present work shows that high-throughput label-free electrical detection of biomolecules such as proteins or DNA can be achieved by direct detection of the OCP with suitable multiplexed instrumentation. DNA hybridisation and binding of intercalator compounds to DNA has been detected with the system.