DynamicOrgan System: Open Organ-on-Chip Platform Demo

Multi-organ chips are miniaturized devices containing 3D organ models connected by nutrient channels pumped by heart-simulating devices. Each organ has a minimum functional unit of approximately 10mm scale, 100,000 times smaller than the original. Using Nobel Prize-winning induced pluripotent stem cell technology, researchers can generate all organ types from a single blood sample, enabling simulation of 16 out of 34 human organs including liver, kidney, and pancreas. The liver processes all substances within 500 micrometers, making rapid toxicity assessment critical. This technology allows testing drug effects on personalized organ models, potentially replacing animal testing.

Pump-based organ-on-a-chip systems consist of interconnected compartments separated by semi-flexible PDMS membranes with glass support layers. Air pumps create pressure differentials that flex membrane walls, generating fluid flow through the system. This architecture enables independent control of flow rates and pressures in different compartments, supporting sophisticated multi-organ modeling. Fluid flow dramatically alters cellular behavior—endothelial cells grown under flow conditions align along flow direction, develop elongated shapes, and form organized vascular structures resembling native blood vessels, demonstrating mechanotransduction where mechanical forces are transduced through the cytoskeleton to trigger intracellular signaling pathways. Induced pluripotent stem cells can be differentiated into functional podocytes through 10-day protocols, though they pose significant safety hazards if accidentally exposed. Multi-organ chip systems integrate intestinal, brain, liver, and kidney compartments connected by shared blood circuits to model complete ADME profiles. Kidney-on-a-chip systems incorporate dual circulation circuits where blood and urine circuits interact only at specific points where glomerular and proximal tubule cells are seeded on semi-porous membranes. The ultimate vision is human-on-a-chip systems enabling personalized medicine through patient-derived iPSCs, though current implementation faces significant barriers including lack of standardization, high costs ($60,000+ for equipment, €150 per chip), limited scalability, and labor-intensive operation requiring specialized training.

Scientists have developed a human body-on-a-chip system containing five chambers with different cell types connected by channels that circulate nutrient solution simulating blood flow, enabling simultaneous testing of drugs on multiple cell types including cancer cells, cardiac cells, and liver cells without requiring animal testing.

Multi-organ chips integrate multiple organ models through shared circulation systems to replicate human physiology. Key design principles include maintaining near-physiological circulation for growth factor and cytokine exchange, enabling organs to interconnect and communicate. Chips accommodate various cell sources (iPSCs, primary cells, biopsies) and formats (2D cultures, spheroids, organoids). The experimental workflow involves preparing organ models, transferring to chips at day zero, culturing for 1-4 weeks, and sampling for metabolite analysis (LCMS), viability assessment (LDH, ALT, albumin), and functional measurements. Endpoint analysis includes histology, qPCR, sequencing, and permeation studies.

Organ-on-a-chip technology represents a revolutionary approach to biological research using microphysiological systems that simulate physiological conditions without electrodes. These systems enable continuous monitoring of parameters like temperature and can represent functional biological units such as the liver containing approximately one million cells. The technology allows researchers to study drug metabolism and systemic delivery across biological barriers, with systems operable for extended periods up to 28 days while allowing extraction and analysis of metabolic markers. Multi-organ systems can reveal interactions between different organs that would not be apparent when studying organs in isolation, simulating blood circulation using dual circulation loops. The technology can accept human biopsies, bridging the gap between animal models and human physiology, and can model various organs including the liver, kidneys, skin, and bones through different administration routes.

High-throughput screening (HTS) is a laboratory-based experimental screening process that uses robotic technology to test large numbers of compound derivatives against biological targets. Unlike virtual screening, HTS uses real chemical compounds and automated equipment (robotic arms, plate readers) to perform biological assays. While faster than manual screening, HTS requires significant resources including large quantities of chemicals, specialized hardware, and produces highly biologically relevant results that validate computational predictions.

High-throughput screening (HTS) is a robotic-based methodology that enables researchers to rapidly conduct millions of chemical, genetic, or pharmacological tests using microtiter plates (typically 384, 1536, or 3456 wells) to identify active compounds, antibodies, or genes that modulate specific biomolecular pathways; the process involves preparing assay plates from stock compound libraries, measuring biological responses through automated analysis systems, and applying statistical methods including Z-scores, signal-to-noise ratios, and strictly standardized mean difference (SSMD) for quality control and hit selection, with recent advances in microfluidics enabling screening speeds up to 1,000 times faster than conventional techniques.

High throughput screening (HTS) is one of the most important and effective screening methods for screening compounds. All 5000 to 10,000 active compounds are screened for the ability to interact with the identified target using HTS. This method uses robotics, data processing, control software, liquid handling devices, and sensitive detectors to rapidly conduct millions of pharmacological, chemical, and genetic tests. More than 50,000 compounds can be screened in a day. From 5000 to 10,000 compounds, only around 100 to 200 compounds are identified with affinity and selectivity for the identified targets, and these compounds are called hits.

High-Throughput Screening (HTS) is an experimental approach used by research institutions with strong economic resources, including major universities and pharmaceutical laboratories. In HTS, researchers have access to large physical compound libraries and simultaneously test all compounds against a specific biological target to identify molecules with potential activity. This process is expensive and time-consuming.

High Throughput Screening (HTS) or High Throughput Experimentation (HTE) is a scientific research methodology that accelerates experimentation through automation, parallelization, miniaturization, and intelligent experiment design, enabling simultaneous execution of multiple experiments (up to 80 synthesis reactions) with real-time analytics and 24-hour operation to reduce time-to-market for new products.

Regulatory science is best defined as translational science. It involves translating the latest advances in technology to mechanisms that facilitate safe and effective delivery of tools and technologies to the point of care. Regulatory agencies must take a proactive posture, requiring a collaborative mindset where they focus on advancing public health rather than simply approving or rejecting products. This involves research on the ground and helping de-risk tools and technologies with innovators.

The translation of regulatory science research into formal guidance involves significant lag times—research conducted in the mid-1990s on xenotransplantation infectious risks did not result in written guidance until several years later, with final documents issued in 2003. The FDA's intramural and extramural research programs, including Centers of Excellence in Regulatory Science, support proactive addressing of regulatory science gaps while maintaining in-house capability to respond to public health emergencies. The researcher reviewer model enables daily advice to sponsors during development periods, with open public workshops and advisory committees facilitating stakeholder engagement throughout the regulatory process.

Regulatory science is the discipline that develops knowledge, tools, standards, and approaches to evaluate the safety, effectiveness, and quality of medical products and foods, transforming scientific discoveries into practical healthcare solutions through methods like whole genome sequencing for pathogen tracking, precision medicine for targeted treatments, and advanced technologies such as brain-computer interfaces for prosthetics.

Regulatory science is important for improving regulatory standards, procedures, and decision-making in drug development. Regulatory systems are never perfect and evolve over time, exposed to push and pull dynamics from new innovations and societal mechanisms (like orphan drug legislation). The Regulatory Science Network Netherlands brings together regulators, industry, academia, and patient representatives to discuss how regulatory systems can be improved. A study of new orphan drugs approved in 2016-2020 found that 13 were from repurposing trajectories, and 3 out of 4 came from academia, showing a substantial contribution of academia to repurposing in rare diseases. Regulatory science aims to map regulatory issues across drug development dossiers to understand where applicants come from, what hurdles they face, what data should be provided, and where extra investment is needed. The approach involves three layers: easy support to help developers understand where to go and what is important at what time, think tanking to look at systems and improve individual projects, and more detailed support using frameworks like technology readiness levels. The goal is to bring regulatory science closer to academic drug development through systematic mapping of regulatory issues across dossiers. The panel discussion addressed key challenges including building dialogue between academia, regulators, and industry, national expertise centers and funding, political support, innovation and disruptive approaches, patient education and involvement, and knowledge sharing.

Regulatory science and translational medicine bridge basic research discoveries to clinical applications and regulatory approval processes. Research areas include developing laboratory assays to predict clinical outcomes, investigating transdermal drug delivery optimization, and examining neuroinflammatory mechanisms in traumatic brain injury. The field requires understanding both scientific rigor and regulatory requirements to advance therapies through clinical development pipelines. Professionals work across academic, industry, and government sectors to ensure safe and effective translation of scientific discoveries into medical practice.