A Microfluidic Experimental Method for Studying Cell-to-Cell Exosome Delivery-Taking Stem Cell-Tumor Cell Interaction as a Case.

Cell-to-cell communication must occur through molecular transport in the intercellular fluid space. Nanoparticles, such as exosomes, diffuse or move more slowly in fluids than small molecules. To find a microfluidic technology for real-time exosome experiments on intercellular communication between living cells, we use the microfluidic culture dish's quaternary ultra-slow microcirculation flow field to accumulate nanoparticles in a specific area. Taking stem cell-tumor cell interaction as an example, the ultra-slow microcirculatory flow field controls stem cell exosomes to interfere with tumor cells remotely. Under static coculture conditions (without microfluidics), the tumor cells near stem cells (<200 µm) show quick breaking through from its Matrigel drop to meet stem cells, but this 'breaking through' quickly disappears with increasing distance. In programmed ultra-slow microcirculation, stem cells induce tumor cells 5000 µm far at the site of exosome deposition (according to nanoparticle simulations). After 14 days of programmed coculture, the glomeration and migration of tumor cells were observed in the exosome deposition area. This example shows that the ultra-slow microcirculation of the microfluidic culture dish has good prospects in quantitative experiments to study exosome communication between living cells and drug development of cancer metastasis.

Manipulating nanoliter fluid circuits on an all-glass chip by the magnetic field.

Actively controlled nanoliter fluid circuits are an urgently needed technology in electronics, biomedicine, chemical synthesis, and biosensing. The difficulty lies in how to drive the microfluid in an isolated and airtight manner in glass wafer. We used a magnetic oscillator pump to realize the switching of the circulation direction and controlling the flow rate of the 10nL fluid. Results of two-dimensional numerical simulations shows that the flow field can reach a steady state and a stable flow can be obtained. The contribution of each vibration cycle to the flow rate is proportional to the frequency, decays exponentially with the viscosity, is proportional to the 4.2 power of the amplitude, and is proportional to the radius. Compared with the existing fluid technology, this technology realizes the steering and flow control of a fully enclosed magnetic control fluid circuit as small as 10nL in hard materials for the first time.

A pandemic-enabled comparison of discovery platforms demonstrates a naïve antibody library can match the best immune-sourced antibodies.

As a result of the SARS-CoV-2 pandemic numerous scientific groups have generated antibodies against a single target: the CoV-2 spike antigen. This has provided an unprecedented opportunity to compare the efficacy of different methods and the specificities and qualities of the antibodies generated by those methods. Generally, the most potent neutralizing antibodies have been generated from convalescent patients and immunized animals, with non-immune phage libraries usually yielding significantly less potent antibodies. Here, we show that it is possible to generate ultra-potent (IC50 < 2 ng/ml) human neutralizing antibodies directly from a unique semisynthetic naïve antibody library format with affinities, developability properties and neutralization activities comparable to the best from hyperimmune sources. This demonstrates that appropriately designed and constructed naïve antibody libraries can effectively compete with immunization to directly provide therapeutic antibodies against a viral pathogen, without the need for immune sources or downstream optimization.