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SELECTBIO Conferences Flow Chemistry Summit 2021

Flow Chemistry Summit 2021 Agenda

Thursday, 30 September 2021


Conference Registration, Materials Pick-Up, Morning Coffee and Pastries

Session Title: Conference Opening Session -- Flow Chemistry Summit 2021 and The Space Summit 2021


Paul WattsConference Chair

Conference Welcome and Introduction by Conference Chairperson -- Flow Chemistry: Current and Future Advances
Paul Watts, Distinguished Professor and Research Chair, Nelson Mandela University, South Africa


Welcome and Introduction to the Space Summit 2021: Impact of Microgravity on Biological and Physical Systems
Marc Giulianotti, Program Director, International Space Station U.S. National Laboratory, United States of America


NIH NCATS Tissue Chips in Space
Danilo Tagle, Director, Office of Special Initiatives, National Center for Advancing Translational Sciences at the NIH (NCATS), United States of America


Bioprinting of Living Tissue Constructs For Space Exploration
Michael Gelinsky, Professor, Technical University Dresden, Germany

For long-term space exploratory missions and extra-terrestrial human settlements, e. g. on Moon or Mars, the astronauts must be able to treat health problems on site as a fast return to Earth is impossible. 3D bioprinting is a promising technology which might allow fabrication of tissue constructs like skin and bone with limited equipment and materials which mostly could be produced locally. The presentation will give an overview about a study on bioprinting for space exploration which recently was carried out for the European Space Agency (ESA). We have investigated different bioprinting technologies, suitable biomaterials and also possible medical scenarios in which bioprinting might become an important tool.


Morning Coffee Break and Networking


CELLINKEffect of Microgravity on Bioprinted Tissues
Nicole Diamantides, Bioprinting Field Application Scientist, CELLINK

Bioprinting can be used to fabricate functional living tissues. These tissues can be used for a variety of applications from drug testing, studying disease pathology, regenerative medicine, and more. Recently, microgravity has been utilized both for understanding how tissues will respond to space travel and as a negative control for understanding how gravitation forces affect tissue formation and disease development. Here, we will discuss how the gene expression of stem cells is affected by space flight and simulated microgravity and how simulated microgravity can be used to understand glioblastoma mechanical regulation.


What Can Biofabrication do for Space and what can Space do for Biofabrication?
Lorenzo Moroni, Professor, Biofabrication for Regenerative Medicine, Maastricht University and Founder MERLN Institute for Technology-Inspired Regenerative Medicine, Netherlands

Biofabrication in space, and in particular bioprinting, is one of the novel promising and perspective research directions in the rapidly emerging field of space biomedical sciences. There are several advantages of bioprinting in space. First, under the conditions of microgravity (µg), it is possible to bioprint constructs employing more fluidic channels and, thus, more biocompatible bioinks. Second, µg conditions enable 3D bioprinting of tissue and organ constructs of more complex geometries with voids, cavities, and tunnels. Third, a novel scaffold-free, label-free, and nozzle-free technology based on multi-levitation principles can be implemented under the condition of µg. The ideal space bioprinters must be safe, automated, compact, and user friendly. Thus, there are no doubts that systematic exploration of 3D bioprinting in space will advance biofabrication and bioprinting technology per se. Vice versa 3D bioprinted tissues could be used to study pathophysiological biological phenomena, when exposed to µg and cosmic radiation that will be useful on Earth to understand ageing conditioning of tissues, and in space for the crew of deep space manned missions. Here, we provide some leading concepts on what mutual benefit can be drawn by the application of biofabrication technologies in space, and sketch a future scenario where such marriage could enable advancements in space biological programs and of our ageing society.


Tissue Chips in Space: Human Cartilage-Bone-Synovium Microphysiological System for Post-Traumatic Osteoarthritis
Alan Grodzinsky, Professor of Biological, Electrical and Mechanical Engineering, Director of the MIT Center for Biomedical Engineering, Massachusetts Institute of Technology (MIT), United States of America

Post-traumatic osteoarthritis (PTOA) is caused by a traumatic impact joint injury associated with an augmented inflammatory environment (such as an ACL rupture). This results in loss of cartilage and impaired joint function, severely impacting the quality of life of otherwise healthy individuals, compounded by the fact that there are no disease-modifying drugs available for OA/PTOA, only short acting pain killers that do not halt disease progression. Astronauts may be at heightened risk of altered musculoskeletal physiology, thus impacting their Space mission. With an aim of PTOA disease management on Earth and supporting astronaut health during long space missions, our overall objective has been to develop a microphysiological system (MPS) to simulate aspects of PTOA pathogenesis and progression in vitro, and to use this MPS to develop therapeutic regimens incorporating appropriate drugs and dynamic exercise loading to prevent disease progression and stimulate pro-anabolic responses. Analyses to date from ISS experiments show changes in human knee tissues indicative of the earliest events in the initiation and progression of PTOA. The effects of human variability are also under study. Use of such an MPS on earth and in LEO-based platforms could enable accelerated disease modeling, providing unique insights into disease progression and development of therapeutic interventions. Effects of altered loading of joint cartilage in space may affect the rate of cartilage breakdown leading to OA. Microgravity may uniquely enable the study of joint-disuse versus exercise in management of OA and PTOA.


Networking Lunch


One-Step Gene Sampler Tool for Genetic Analysis on ISS
Gergana Nestorova, James C. Jeffrey, M.D. Endowed Professorship in Pre-Med, Louisiana Tech University, United States of America

The aim to support an extended human presence in space has led to the establishment of NASA’s GeneLab, which combines a database repository dedicated to ISS biological experiments and corresponding ground-based studies. The biggest constraints for real-time genetic analysis of biological specimens in space are the time that is required for the astronaut to process the sample and the reduced working area on ISS. Because of these limitations, the number of samples that are currently being analyzed in space is very low. The One-Step Gene Sampler tool can significantly reduce the time required for genetic analysis on ISS and therefore could increase the number of samples analyzed in space. This presentation will discuss the design, application, and validation of this technology on ISS. At the core of this tool is a microscopic pin for the purification of nucleic acid that is analyzed by the WetLab-2  facility currently on station. The Gene Sampler tool can be used for RNA purification at various locations of the biological sample and does not require sacrificing of the specimen. Most valuably, the probes need no further processing to separate RNA from the sample. The specimen’s RNA hybridizes to the surface of the probe and no nuclear contamination occurs. Sampling is completed after a minimum of two-minute insertion into the specimen and the probe can be analyzed directly in the ISS SmartCycler instrument. Instead of using the conventional liquid-based process, the purification of genetic material now can be performed dry, utilizing a functionalized metal pin that is compatible with the ISS environment and analytical tools. The technology was launched on SpaceX CRS-21 and validated by Dr. Kate Rubins in February 2021.


Human Multi-Tissue Platform to Study Effects of Space Radiation and Countermeasures
Gordana Vunjak-Novakovic, University Professor, Columbia University, United States of America

Cosmic radiation is the most serious risk encountered during long missions to the Moon and Mars. There is a compelling need to understand the exact effects of cosmic radiation, safety thresholds, and mechanisms of various types of tissue damage, in order to develop measures for radiation protection during extended space travel. As animal models fail to recapitulate the exact mutational changes expected for astronauts, engineered human tissues and “organs-on-a-chip” are valuable tools for studying effects of radiation in vitro. We have developed bioengineered tissue platforms in which we can study radiation damage in a patient-specific setting. All tissues are derived from induced pluripotent stem cells cultured for a period of 4-6 weeks and matured to match some aspects of human physiology. We describe here the studies of radiation effects on bone marrow (a site of acute radiation damage) and cardiac muscle (a site of chronic radiation damage). To this end, we investigated the effects of simulated high-LET cosmic ray exposures, both acute and protracted, on human tissues connected by vascular perfusion. We propose that the engineered human tissue systems can provide test beds for radioprotective therapeutics to mitigate radiation damage during space exploration.


The NATO Project: Nanoparticle-based Countermeasures for Microgravity-induced Osteoporosis
Livia Visai, Associate Professor, University of Pavia, Italy

Recent advances in nanotechnology applied to medicine and regenerative medicine have an enormous and unexploited potential for future space and terrestrial medical applications. The Nanoparticles and Osteoporosis (NATO) project aimed to develop innovative countermeasures for secondary osteoporosis affecting astronauts after prolonged periods in space microgravity. Calcium- and Strontium-containing hydroxyapatite nanoparticles (nCa-HAP and nSr-HAP, respectively) were previously developed and chemically characterized. This study constitutes the first investigation of the effect of the exogenous addition of nCa-HAP and nSr-HAP on bone remodeling in gravity (1 g), Random Positioning Machine (RPM) and onboard International Space Station (ISS) using human bone marrow mesenchymal stem cells (hBMMSCs). In 1 g conditions, nSr-HAP accelerated and improved the commitment of cells to differentiate towards osteoblasts, as shown by the augmented alkaline phosphatase (ALP) activity and the up-regulation of the expression of bone marker genes, supporting the increased extracellular bone matrix deposition and mineralization. The nSr-HAP treatment exerted a protective effect on the microgravity-induced reduction of ALP activity in RPM samples, and a promoting effect on the deposition of hydroxyapatite crystals in either ISS or 1 g samples. The results indicate the exogenous addition of nSr-HAP could be potentially used to deliver Sr to bone tissue and promote its regeneration, as component of bone substitute synthetic materials and additive for pharmaceutical preparation or food supplementary for systemic distribution.


Afternoon Coffee Break and Networking


Paul WattsKeynote Presentation

Drugs for Africa: Process Intensification for API Synthesis Exploiting Continuous Manufacturing
Paul Watts, Distinguished Professor and Research Chair, Nelson Mandela University, South Africa

While Africa has a variety of companies that formulate medicines, it does not have any form of pharmaceutical industry that manufactures the active pharmaceutical ingredients (APIs) with the consequence that these need to be imported. This results in increased drug costs making medications unaffordable to most patients in Africa. The current pandemic has further demonstrated supply chain issues when relying entirely on imported products.

To this effect, we are working on developing local drug manufacturing capacity in Africa using continuous flow technology, with the goal of lowering the cost of drugs, improving drug accessibility and ultimately improving Africa’s health. We are developing cost effective and efficient continuous flow synthetic processes towards a variety of drugs to demonstrate that they can be manufactured at lower cost in Africa. The presentation will give a few case studies.


Continuous-Flow Approach Towards Synthetic CBD
Rodrigo Souza, Associate Professor, Federal University of Rio de Janeiro, Brazil

Recently, CBD was included in some countries as an antiepileptic product for compassionate use in children with refractory epilepsy. With the growth in the demand of CBD, comes a need for high purity-grade cannabinoids for the emerging market. The discovery and development of approaches toward cannabidiol synthesis have emerged from the extraction of the cannabis plants to cannabinoid fermentation in brewer’s yeast successfully. Here in we present our approach towards synthetic CBD by means fo continuous-flow protocol.


Automated Flow Platforms with In-Built Flexibility – Radial Synthesis and Beyond
Kerry Gilmore, Assistant Professor, University of Connecticut, United States of America

Automated flow chemistry platforms have the capability to significantly accelerate and standardize the development and study of organic chemistry reactions and processes. However, one limitation of the general approach is the design of custom systems for specific targets or processes. This requires physical reconfiguration of the system to perform the next “unique” process. By decoupling sequential process steps, an incredible degree of flexibility is introduced into a multistep continuous process. This approach affords numerous capabilities unavailable in a traditional flow system. In this talk, we will discuss how automated platforms using this approach create the opportunity for one-stop systems for fully remote research and data generation.


New Frontiers in Flow Technology and Reaction Processes
Aaron Beeler, Assistant Professor, Boston University, United States of America

In the Beeler Research Group, we are developing new technologies and approaches that can be applied to natural product synthesis and medicinal chemistry. The lecture will highlight developments in challenging reactions which can be used to access complex small molecules which are critical in our multidisciplinary and collaborative research. A common theme in our lab is the use of flow chemistry to develop efficient reactions and processes that overcome limiting boundaries that are prevalent in batch reactions. Flow chemistry allows us to reconsider the utility of many transformations for applications in synthesis, such as photochemical reactions of cinnamates to access complex cyclobutanes and visible light excitation of pyridinium ylides to afford azepines and related analogues. I hope to demonstrate how flow chemistry provides us a tool for development of new and more efficient reactions that are robust, highly scalable, and provide access to complex and novel chemotypes.


Paul BohnKeynote Presentation

Fluidically-Coupled Electrochemical Immunosensing of Interleukin-6 in as a Biomarker for Traumatic Brain Injury and Covid-Related Cytokine Storms
Paul Bohn, Arthur J. Schmitt Professor of Chemical and Biomolecular Engineering and Professor of Chemistry and Biochemistry, University of Notre Dame, United States of America

A highly sensitive, label-free immunosensing platform based on interdigitated electrode arrays (IDEAs) has been developed for the detection of IL-6, a critical cytokine biomarker for inflammation and trauma. The IL-6 IDEA sensor exhibits a LOD in PBS that is comparable to other label-free sensors and ELISA-based electrochemical immunosensors, and it achieves linear ranges at IL-6 concentrations across 4 orders of magnitude for all fluids. Thus, the IL-6 IDEA sensor is an excellent candidate for clinical application as a POC tool, given its simple assembly, ease of operation, straightforward analysis, and good sensitivity for IL-6 in physiological fluids. Furthermore, preliminary experiments on non-optimized structures show that operation in generator-collector redox cycling mode can produce significant amplification factors. The performance of the IL-6 IDEA sensor was also explored in both CSF and serum. The IDEA sensor is less sensitive to IL-6 in CSF and serum than in in PBS, which is expected due to the presence of interferents, such as cellular debris, proteins, lipids, etc. Although LODs in CSF and serum were higher, the IL-6 IDEA electrochemical immunosensor can reliably detect IL-6 across 4 orders of magnitude at clinically relevant concentrations in CSF and serum. CSF is the preferred physiological fluid for biomarker detection due to its exceptionally low concentration of non-target interferents relative to blood plasma or serum.


Challenges and Benefits of Implementing Integrated Continuous Manufacturing (ICM) Beyond the Laboratory
Bayan Takizawa, Chief Business Officer, CONTINUUS Pharmaceuticals, Inc., United States of America

Recently, there has been increased interest in the application of continuous manufacturing to pharmaceuticals. The advantages are undeniable, as many other industries have evolved their production systems, enjoying the improved efficiencies and lower costs associated with continuous manufacturing. Pharma, conversely, has been slower to adapt, clinging to outdated batch methods and fragmented supply chains that are vulnerable to disruptions, which ultimately impact patient care. Fortunately, more and more companies are embracing continuous manufacturing, several receiving approvals of continuously produced drug products in recent years. This presentation will focus on some of the challenges in implementing continuous manufacturing in the pharma industry, but also show why change is imminent. Regulatory, quality, cultural, and other relevant factors will be discussed.


Close of Day 1 of the Conference

Friday, 1 October 2021


Morning Coffee, Pastries and Networking


Chairperson's Opening Remarks: Bringing Together Flow Chemistry and Space Chemistry
Jana Stoudemire, Director, In-Space Manufacturing, Axiom Space, United States of America


In-Line Analysis In Flow: The Gateway to Smart Synthesis and Machine Learning in Chemistry
Michael Organ, Professor and Director of the Centre for Catalysis Research and Innovation , University of Ottawa, Canada

In-process reaction monitoring with GCMS, LCMS, and NMR spectroscopy has been developed to accurately track reaction performance. This has facilitated the incorporation of feed-back loops between the reactor effluent stream and the front end of the reactor using in-house developed software for hands-free continuous reaction optimization and production monitoring. Of course, samples must first be extracted from continuous processes in order to perform the above mentioned in-line analysis. This is often times thwarted by the presence of solids in the flowing stream, which can both block lines and valves and make analyses inaccurate. We have developed technology for the reliable handling of samples that contain solids from flow streams, which will be discussed.


Klavs JensenKeynote Presentation

Automation, Machine Learning, and Robotics for Flow Chemistry Optimization
Klavs Jensen, Professor, Massachusetts Institute Of Technology, United States of America

Advances in flow chemistry enabled by automation, machine learning, robotics, and on-line analytics  are highlighted through case studies, including an automated droplet microfluidic electrochemistry platform for redox neutral electrochemistry, reaction optimization and characterization of kinetics, (2) an automated cascade of miniaturized continuous stirred tank reactors (CSTRs) for optimization of flow chemistry and photo-redox catalysis involving suspensions of solids, and (3) an automatic, robot assembled, reconfigurable modular micro/mini-fluidic system for execution and optimization of multistep reactions. Machine learning models for retrosynthesis and forward prediction combined with reaction context identification provide computer aided synthesis pathway planning for this system.  We describe and compare different optimization strategies and discuss challenges and opportunities in further integration of machine learning and synthesis platforms.


Volker HesselKeynote Presentation

Microfluidic Systems based on Multi-phase Designer Solvents with Aim to Automate Purification and Recycling Reactants
Volker Hessel, Professor, School of Chemical Engineering, The University of Adelaide, Australia

Novel Process Windows with their unusual, typically harsh process conditions have enlarged the processing portfolio. Recently, we have developed a biomimetic processing concept that aims to develop flexible compartments for integrated reactions in a way as organelles (vacuoles) in a cell do. The compartments are formed by self-organising media by multi-phase designer solvents. In this way, cascade reactions may be run automatically in just one reactor (ONE-FLOW), which is compartmented to the complexity needed.

The presentation will show (1) the use of solubility modelling for finding the best solvents out of a myriad of choices, (2) the performance/opportunity and problems at a model reaction with organocatalyst, (3) the performance/opportunity and problems at a model reaction with enzyme catalyst, (4) a life cycle assessment for an industrial process (3-step ibuprofen) under favourable assumptions and tailored to the idea, (5) a life cycle assessment for an industrial process (1-step or 2-step rufinamide) under reported industrial conditions and not ideally tailored to the idea,  and (6) a comparison of all classes of designer solvent per life cycle assessment impact category; the latter comprises ionic liquids, scCO2, fluorous solvents, thermomorphic solvents, and deep eutectic solvents.


Mid-Morning Coffee Break and Networking


Amanda EvansKeynote Presentation

Continuous Flow in the High Desert: Tales from Los Alamos National Laboratory
Amanda Evans, Scientist, Los Alamos National Laboratory, United States of America

Los Alamos National Laboratory (LANL) has a long history of using state-of-the-art technologies for making molecules and developing processes fundamental for securing the defense of the United States. Continuous flow processing paradigms and inline analytical technologies provide unique avenues for safely optimizing and scaling chemical syntheses while affording improved understanding and control of reaction kinetics. Examples of integration of continuous flow and inline analytics into diverse production practices at LANL will be presented, as will a discussion of how U.S. national labs (inclusive of the ISS) can benefit from the innovations that flow chemistry can provide for materials and medical countermeasures production.


In Space Production, Chemistry and Crystals
Ken Savin, Senior Program Director, In Space Production, International Space Station US National Lab, United States of America

Access to the microgravity environment of Low Earth Orbit offers industry production opportunities not possible terrestrially. This presentation will focus on ISS National Lab efforts around in-space production, manufacturing processes and intellectual-property generation with a focus on chemistry applications that enable new business growth and represent markets that could generate revenue from access to space. This is a unique opportunity to keep up with the production and IP opportunities for advanced materials products and pharmaceuticals.


Accelerated Development of Quantum Dots by Autonomous Robotic Experimentation in Flow
Milad Abolhasani, Associate Professor , North Carolina State University, United States of America

In this talk, I will present the Artificial Chemist technology, that is, a modular flow chemistry platform operated by a machine learning-guided decision-making algorithm for accelerated development of energy-relevant colloidal nanomaterials. I will discuss the unique advantages of reconfigurable flow reactors for autonomous multi-step synthesis, optimization, and continuous manufacturing of colloidal quantum dots (QDs) for direct utilization in next-generation photonic devices. The Artificial Chemist can rapidly and efficiently (i) explore and learn the synthesis and processing universe of colloidal QDs, (ii) identify the composition and relevant synthesis and processing route(s) of QDs to achieve specific optical or optoelectronic properties, and (iii) continuously manufacture the rapidly optimized QDs at a fraction of time/cost of currently utilized batch techniques. The developed autonomous robotic experimentation strategy can be readily adapted for accelerated development and end-to-end manufacturing of other solution-processed nanomaterials.


Networking Lunch


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