Optical Imaging of the Nanoscale Structure and Dynamics of Biological Membranes

Biological membranes serve as the fundamental unit of life, allowing the compartmentalization of cellular contents into subunits with specific functions. The bilayer structure, consisting of lipids, proteins, small molecules, and sugars, also serves many other complex functions in addition to maintaining the relative stability of the inner compartments. Signal transduction, regulation of solute exchange, active transport, and energy transduction through ion gradients all take place at biological membranes, primarily with the assistance of membrane proteins. For these functions, membrane structure is often critical. The fluid-mosaic model introduced by Singer and Nicolson in 1972 evokes the dynamic and fluid nature of biological membranes.(1) According to this model, integral and peripheral proteins are oriented in a viscous phospholipid bilayer. Both proteins and lipids can diffuse laterally through the two-dimensional structure. Modern experimental evidence has shown, however, that the structure of the membrane is considerably more complex; various domains in the biological membranes, such as lipid rafts and confinement regions, form a more complicated molecular organization. The proper organization and dynamics of the membrane components are critical for the function of the entire cell. For example, cell signaling is often initiated at biological membranes and requires receptors to diffuse and assemble into complexes and clusters, and the resulting downstream events have consequences throughout the cell. Revealing the molecular level details of these signaling events is the foundation to understanding numerous unsolved questions regarding cellular life

AC and DC Differential Bridge Structure Suitable for Electrochemical Interfacial Capacitance Biosensing Applications

This paper presents a capacitive differential bridge structure with both AC and DC excitation and balancing capability for low cost electrode-solution interfacial capacitance biosensing applications. The proposed series RC balancing structure offers higher sensitivity, lower susceptibility to common-mode interferences, and drift control. To evaluate the bridge performance in practice, possible effects of initial bridge imbalance due to component mismatches are investigated considering the required resolution of the balancing networks, sensitivity, and linearity. This evaluation is also a guideline to designing the balancing networks, balancing algorithm and the proceeding readout interface circuitry. The proposed series RC bridge structure is implemented along with a custom single frequency real-time amplification/filtering readout board with real-time data acquisition and sine fitting. The main specifications for the implemented structure are 8-bit detection resolution if the total expected fractional capacitance change at the interface is roughly 1%. The characterization and measurement results show the effectiveness of the proposed structure in achieving the design target. The implemented structure successfully achieves distinct detection levels for tiny total capacitance change at the electrode-solution interface, utilizing Microcystin-(Leucine-Arginine) toxin dilutions as a proof of concept