Bioelectronic properties of DNA, protein, cells and their applications for diagnostic medical devices.

From a couple of centuries ago, understanding physical properties of biological material, their interference with their natural host and their potential manipulation for employment as a conductor in medical devices, has gathered substantial interest in the field of bioelectronics. With the fast-emerging technologies for fabrication of diagnostic modalities, wearable biosensors and implantable devices, which electrical components are of essential importance, a need for developing novel conductors within such devices has evolved over the past decades. As the possibility of electron transport within small biological molecules, such as DNA and proteins, as well as larger elements such as cells was established, several discoveries of the modern charge characterization technologies were evolved. Development of Electrochemical Scanning Tunneling Microscopy and Nuclear Magnetic Resonance among many other techniques were of vital importance, following the discoveries made in sub-micron scales of biological material. This review covers the most recent understandings of electronic properties within different scale of biological material starting from nanometer range to millimeter-sized organs. We also discuss the state-of-the-art technology that's been made taking advantage of electronic properties of biological material for addressing diseases like Parkinson's Disease and Epilepsy.

Thermally Assisted Acoustofluidic Separation Based on Membrane Protein Content.

The over- and under-expression of certain proteins in extracellular vesicles has been observed in many physiological and pathological conditions; however, a simple method to sort vesicles based on contrast in protein content is yet to be developed. We herein present a nonaffinity-based method for rapid and inexpensive isolation of lipid vesicles based on their membrane protein content. Based on a composition-specific thermophysical property change of vesicles at different protein contents, an acoustic property change that enabled an acoustophoretic separation was observed. This change was demonstrated in a thermally modulated acoustofluidic device in the form of a shift in vesicle migration from the nodal plane to antinodal plane at a specific temperature known as the acoustic contrast temperature (TΦ). Using phosphatidylcholine vesicles containing the membrane proteins gramicidin D, alamethicin, and melittin at molar contents ranging from 0.001% to 10%, we observed that increasing the membrane protein content brought about conformational changes in the membrane which afforded the vesicles distinctive acoustic properties. Then, by establishing an acoustic contrast temperature window, vesicles with the same protein but different molar content were successfully separated. The efficiency of the separation was studied for various vesicle mixtures and a separation efficiency as high as 97% was accomplished. In order to confirm the technique's applicability for biological samples, sheep red blood cells with various melittin peptide contents similarly demonstrated the depressing effects of melittin on membrane bending modulus and depressed the TΦ of the cells. This method holds promise for a myriad of applications in the biomedical field, especially in bioanalytical research.

Thermo-acoustofluidic separation of vesicles based on cholesterol content.

Biomechanical properties of cells such as cellular stiffness have been increasingly considered as biomarkers for diseases. For instance, stiffness of cancer cells has been correlated to the malignant potential in certain cell lines. In cells, the cholesterol content plays a crucial role in determining stiffness. Changes in the cholesterol content in cellular membranes can be an indication of pathological disorders. Acoustophoresis as a separation and diagnostic tool is well positioned to help in the separation and diagnosis of cells taking advantage of its unique separation criteria of density and compressibility. However, under the same conditions, cells and vesicles secreted by these cells often have a positive contrast factor sign and thus do not yield simple separations. Thermally-assisted acoustophoresis, also referred to as thermo-acoustophoresis, solves this problem by adding a temperature dimension to the separation. In this work, we evaluate the acoustic contrast temperature (TΦ) of vesicles at different cholesterol molar ratios (Xchol) and develop a multi-stage lab-on-a-chip method to accomplish for the first time the separation of a three-vesicle mixture. Using Xchol = 0.1, 0.2, and 0.3 vesicles, we have obtained separation efficiencies exceeding 93%. The simplicity, rapidity, and label-free nature of this approach holds promise as a diagnostic and separation tool for cells and extracellular vesicles such as exosomes and microvesicles.