アジェンダ

Nanobiodevices, Quantum Technology, and AI for Future Healthcare
Yoshinobu Baba, Professor, Nagoya University, Japan

We have developed nanobiodevices, quantum technology, and AI for biomedical applications and healthcare, including single cancer cell diagnosis for cancer metastasis, circulating tumor cell (CTC) detection by microfluidic devices, nanopillar devices for ultrafast analysis of genomic DNA and microRNA, nanopore devices for single DNA and microRNA sequencing, nanowire devices for exosome analysis, single-molecular epigenetic analysis, AI-powered nano-IoT sensors, quantum switching intra vital imaging of iPS cells and stem cells, and quantum technology-based cancer theranostics. Immuno-wall microfluidic devices realized the fast and low invasive "from blood to analysis" type biomarker detection of cancer with fM detection sensitivity within 2 min.  Additionally, nanopillar nanofluidic devices give us ultrafast separation of DNA and microRNA within 60 us and nanopillar-nanopore integrated nanobiodevice enables us ultrafast single molecular DNA sequencing.  Nanowire devices are extremely useful to isolate extracellular vesicles from body fluids and vesicle-encapsulated microRNA analysis.  The device composed of a microfluidic substrate with anchored nanowires gives us highly efficient collections of extracellular vesicles in body fluids and in situ extraction for huge numbers of miRNAs (2,500 types) more than the conventional ultracentrifugation method. Nanowire devices gave us the miRNA date for several hundred patients and machine learning system based on these miRNA data enabled us to develop the early-stage diagnosis for lung cancer, brain tumor, pancreas cancer, liver cancer, bladder cancer, prostate cancer, diabetes, heart diseases, and Parkinson disease.  Nanowire-nanopore devices combined with AI (machine learning technique) enable us to develop mobile sensors for SARA-CoV-2, PM2.5, bacteria, and virus in the environment.  Quantum dots and nanodiamonds with nitrogen-vacancy centers are applied to develop quantum-biodevices for single cancer cell diagnosis, single molecular epigenetic analysis, quantum switching intra vital imaging for iPS cell (induced pluripotent stem cells) based regenerative medicine, and quantum photo immuno-therapeutic devices for cancer.

The NIH Microphysiological Systems Program: Tissue Chips for Tools for Drug Development and Precision Medicine
Danilo Tagle, Director, Office of Special Initiatives, National Center for Advancing Translational Sciences at the NIH (NCATS), United States of America

Approximately 30% of drugs have failed in human clinical trials due to adverse reactions despite promising pre-clinical studies, and another 60% fail due to lack of efficacy. A number of these failures can be attributed to poor predictability of human response from animal and 2D in vitro models currently being used in drug development. To address this challenges in drug development, the NIH Tissue Chips or Microphysiological Systems program is developing alternative innovative approaches for more predictive readouts of toxicity or efficacy of candidate drugs. Tissue chips are bioengineered 3D microfluidic platforms utilizing chip technology and human-derived cells and tissues that are intended to mimic tissue cytoarchitecture and functional units of human organs and systems. In addition toxicity studies in drug development, these microfabricated devices are also being used to model various human diseases for assessment of efficacy of candidate therapeutics. A more recent program is the development of "clinical trials on chips" to inform clinical trial design and implementation, and for studies in precision medicine. Presentation will provide a program update and future directions towards widespread use of tissue chip technologies in partnerships with various stakeholders.

Nanoplasmonic Platforms for COVID-19 Vaccine Development
Amy Shen, Professor, Okinawa Institute of Science and Technology Graduate University, Japan

The recent emerging SARS-CoV-2 variants require swift actions in identifying specific antigens and optimizing vaccine development to maximize the humoral response of the patient. Specifically, measuring the specificity and the amount of antibody produced by the host immune system with high throughput and accuracy is crucial to develop timely diagnostics and therapeutic strategies. Motivated by finding an easy-to-use and cost-effective alternative to existing serological methodologies, an optomicrofluidic sensing platform is developed to rapidly detect antibodies against the SARS-CoV-2 spike protein in diluted human plasma within 30 minutes, at the limit of detection of 0.5 pM (0.08 ng/mL). The sensing principle is based on localized surface plasmon resonance (LSPR) involving gold nanospikes (fabricated by electrodeposition) in a microfluidic device, coupled with an optical probe. Extending this work, a nanoplasmonic multiplex optical biosensor to capture the humoral response in serums against Spike from SARS-CoV-2 and two hemagglutinins (HAs) from influenza viruses is established recently. This multiplex assay demonstrates multiple serum antibody profiling by using immunized mice, validated by the ELISA. Our nanofabrication and surface patterning techniques, combined with biotin tag-based protein functionalization method, can be utilized to establish high throughput screening platform for the SARS-CoV-2 vaccine development and beyond.

A Microfluidic Handheld Platform - Flexible Use With and Without Instrument
Claudia Gartner, CEO, microfluidic ChipShop GmbH, Germany

Developing Tools For Disease Diagnostics: From Cancer to COVID-19
Steve Soper, Foundation Distinguished Professor, Director, Center of BioModular Multi-scale System for Precision Medicine, The University of Kansas, Adjunct Professor, Ulsan National Institute of Science & Technology, United States of America

We have been developing tools for the diagnosis of a variety of diseases. The commonality in these tools is that they consist of microfluidic devices made from plastics via injection molding. Thus, our tools can be mass produced at low-cost that facilitates bench-to-bed side transition and point-of-care testing (POCT). We have also been generating novel assays focused on using liquid biopsy samples. Recently, we have focused on developing plastic nanofluidic devices, which provides unique opportunities for single-molecule analyses. In this presentation, I will talk about the evolution of our fabrication efforts of plastic-based microfluidic and nanofluidic devices as well their surface modification to make the devices biocompatible. Then, I will discuss several applications of these devices and the assays for selection of rare liquid biopsy targets from clinical samples and molecular analysis of their contents to help guide disease management. I will use two examples to highlight the utility of these devices: (1) Analysis of circulating tumor cells (CTCs) using microfluidics for the diagnosis of pancreatic ductal adenocarcinoma (PDAC); and (2) detection of COVID-19 using POCT from saliva samples.  PDAC is a deadly disease with a 5-year survival rate <5%. A microfluidic chip for CTC selection consisted of channels surface-decorated with antibodies that could select CTCs directly from whole blood and enumerate them to determine response to therapy or subject them to next generation sequencing to determine a patient's ability to accept certain treatments. The COVID-19 diagnostic accepts saliva samples and searches for SARS-CoV-2 particles and counts the number of virus particles selected using a label-free approach; nano-Coulter Counter chip (nCC). Both steps of the assay were carried out using a microfluidic and nanofluidic device, respectively. The chips were integrated to a control board to allow for sample processing automation with results in <20 min.

Lab on a Particle Technology to Unlock Antibody and Cell Therapy Discovery
Dino Di Carlo, Professor and Vice Chair of Bioengineering, University of California-Los Angeles, United States of America

We have developed 3D-shaped hydrogel microparticle platforms to capture cells, as well as isolate and label their secretions. These "lab on a particle" systems enable sorting cells based on secreted products for the discovery of antibodies, the development of cell lines producing recombinant products, and the selection of functional cells for cell therapies. Each cell and its secreted products can be analyzed using widely available flow cytometers operating at up to a 1000 cells per second. I will discuss our latest results in sorting antigen-specific T cells and mesenchymal stem cells based on secreted cytokines, extracellular vesicles, and growth factors. Cells sorted based on these properties are intact, can regrow, and maintain the selected function over multiple population doublings, enabling cell therapy discovery and manufacturing workflows.

Promoting Microfluidics From the Lab to Real Biomedical Applications
An-Bang Wang, Distinguished Professor, Institute of Applied Mechanics, National Taiwan University, Taiwan

Microfluidics can bring significant advantages in various applications, e.g., chemical reaction, process control and bio-medical detection etc. In the past twenty-five years, we shifted the research topics from different microfluidic components for pure scientific interest, including micropump, microvalve, and micromixer etc., to various integration systems for potential industrial applications, e.g., microreactor / multi-emulsion generators, high-throughput fluid / flow properties analyzor, and the maskless pattern coating system by multi-phase microfluidic technology, etc. Recently, efforts were made for promoting the microfluidic applications in the life science studies and clinical diagnoses with the advantages of fast, easy use, and excellent cost performance. Examples include a sequential lab-on-a-chip control for biomedical point-of-care testing, and an extremely material- and time-saving TDC (Thin-film Direct Coating) microfluidic platform for fast immunoassay and detection, including the fast TDC WB (western blotting) for fast evaluation of neutralizing response to SARS-CoV-2 and fast TDC IHC (Immunohistochemistry).