Exosomal membrane proteins analysis using a silicon nanowire field effect transistor biosensor.

Exosomes are of great significance in clinical diagnosis, due to their high homology with parental generation, which can reflect the pathophysiological status. However, the quantitative and classification detection of exosomes is still faced with the challenges of low sensitivity and complex operation. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a Silicon nanowire field effect transistor biosensor (Si-NW Bio-FET). First, the impact of Debye length on Si-NW Bio-FET detection was investigated through simulation. The simulation results demonstrated that as the Debye length increased, the electrical response to Si-NW produced by charged particle at a certain distance from the surface of Si-NW was greater. A Si-NW Bio-FET modified with specific antibody CD81 on the nanowire was fabricated then used for detection of cell line-derived exosomes, which achieved a low limit of detection (LOD) of 1078 particles/mL in 0.01 × PBS. Furthermore, the Si-NW Bio-FETs modified with specific antibody CD9, CD81 and CD63 respectively, were employed to distinguish exosomes derived from human promyelocytic leukemia (HL-60) cell line in three different states (control group, lipopolysaccharide (LPS) inflammation group, and LPS + Romidepsin (FK228) drug treatment group), which was consistent with nano-flow cytometry. This study provides a highly sensitive method of directly quantifying exosomes without labeling, indicating its potential as a tool for disease surveillance and medication instruction.

Real-time measurement of the trans-epithelial electrical resistance in an organ-on-a-chip during cell proliferation.

The trans-epithelial electrical resistance (TEER) is widely used to quantitatively evaluate cellular barrier function at the organ level in vitro. The measurement of the TEER in organ-on-chips (organ chips) plays a significant role in medical and pharmacological research. However, due to the limitation of the electrical equivalent model for organ chips, the existing TEER measurements usually neglect the changes of the TEER during cell proliferation, resulting in the low accuracy of the measurements. Here, we proposed a new whole-region model of the TEER and developed a real-time TEER measurement system that contains an organ chip with a plate electrode. A whole region circuit model considering the impedance of the non-cell covered region was also established, which enables TEER measurements to be independent of the changes in the cell covered region. The impedance of the non-cell covered region is here attributed to the resistance of the porous membrane. By combining the real-time measurement system and the whole region model, subtle changes in cellular activity during the proliferation stage were measured continuously every 6 minutes and a more sensitive TEER response was obtained. Furthermore, the TEER measurement accuracy was also verified by the real-time measurement of the TEER with stimulation using the permeability enhancer ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). The obtained results indicated that the new proposed whole region model and the real-time measurement system have higher accuracy and greater sensitivity than the traditional model.

Probing electron-atom collision dynamics in gas plasma by high-order harmonic spectroscopy.

Plasma is a complex system involving diverse collisional processes and interactions, such as electron-impact excitation, ionization, recombination, etc. One of the most important methods for studying the properties and dynamics of plasma is to analyze the radiations from plasma. Here, we demonstrate the high-order harmonic (HH) spectroscopy for probing the complex electron-atom collision (EAC) dynamics in a laser-induced gas plasma. These measurements were carried out by using an elliptically polarized pump and a time-delayed linearly polarized probe. The HH spectra from argon and krypton plasmas were recorded by scanning the time delay up to hundreds of picoseconds. We found that the delay-dependent HH yield contains three distinct regions, i.e., the first enhancement, the subsequent suppression, and the final restoration regions. A qualitative analysis shows that these features are clear signatures of the EAC processes and interactions involved in the delay-dependent HH spectroscopy.