Biomolecule sensing is particularly important for pharmaceutical and medical development. In the past few decades, biomolecular sensors have undergone several generations of development with the advances in biology, chemistry, and fabrication technology. Present-day biomolecular sensors often comprise Micro-Total Analysis Systems (μ TAS) with minimization, integration, and intelligence. The final goal is to realize a Lab-on-a-Chip system which integrates fluid control, biomolecule detection, and processing in one single chip. Currently, most of the developed and utilized biomolecular sensors are based on a variety of technologies such as fluorescence probe detection, surface plasmon resonance detection (SPR), ion sensitive field effect transistor detection (ISFET), light addressable potentiometric sensor detection (LAPS), surface acoustic wave detection (SAW), and quartz crystal microbalance detection (QCM), etc.

From the point of view of ease of data acquisition and of simplicity of system integration, the final goal of Lab-on-a-Chip biomolecule sensing seems best achieved by using a direct electrical detection method in future biomolecular sensors. Direct electrical detection methods are advantageous in that no signal conversion is required and, more importantly, because their integration with a fluidic control system is relatively straightforward. Capacitive electrical detection schemes are particularly easily integrated.

In this dissertation, a sub-50 nm capacitor sensing structure integrated with microand nano-fluidic flow control component has been constructed. It is based on a full analysis, design, and fabrication approach, which addresses noise, sensitivity, and integration issues. This device is composed of an integrated microfluidic flow control channel in PDMS and a nanofluidic channel in silicon oxide feeding a nano-gap capacitor sensing structure with gold electrodes. Our integrated analytical system is also capable of selectivity. This can be realized by the immobilization of specific probe and target molecules on the gold electrode surfaces.

The molecule detection capability is based on the electrical capacitance change upon probe and target molecule binding on the gold electrode surfaces (spaced 50 nm) in the nano-gap sensing structure. A result of our nano-gap capacitor sensing structure design and optimization analysis is our being able to reduce background noise from the electrical double layers by using the sub-50 nm gap sensing structure to overlap the electrical double layers. This results in the capacitance from the diffuse layers to increase dramatically, therefore, increase the system sensitivity to capacitance component due to probe and target molecule binding.

The possibility of excellent fluidic flow control through the nano-gap sensing structure for active molecule flow and exchange is accomplished by using a unique integrated nanofluidic flow control component, which consists of the microfluidic flow control channel in PDMS connected with the nanofluidic channel in parallel. This parallel flow control (PFC) configuration uses flow in the microfluidic channel to set up the pressure gradient across the nanofluidic channel. This configuration also facilitates the interfacing between nanofluidic systems and external macro fluidic systems.

We also provide a demonstration of the biomolecule sensing capabilities of our analytical systems. Probe molecules (cysteamine) are first self-assembled on the gold electrodes, and target molecules (quantum dots with carboxyl groups) then are bonded with the probe molecules. Both of binding occurrences are detected by measuring the capacitance change. We are able to detect about 15% capacitance changes with the amino-carboxyl binding occurrence. Optical fluorescence spectra are also obtained to verify that the quantum dots used in this demonstration actually do attach and cause the corresponding capacitance change. This successful electrical detection of the common amino-carboxyl binding process shows the potential detection applications of our systems for other biomolecules.