BioMEMS: Forging New Collaborations Between Biologists and Engineers
November 1st, 2007
My Name is Newly John and I'm at Department of Biomedical Engineering at University of California Irvine. My research involves developing novel biomedical devices and microfluidic devices for neuroscience and stem cell research. Bios And micro foot is a relatively young discipline that has developed over the last maybe five to 10 years, and it uses a lot of the techniques and expertise developed for the integrated circuit industry.
So what we are doing is using the miniaturization methods and approaches developed for integrated circuits to manufacture small devices with small channels and reservoirs, and use that for cell biology applications. Traditionally, most of the biological experiments have been performed on a Petri dish scale. So for the cells, when looking at a cell, which is about 10 microns in diameter, you know, basically we have a small cell that's immersed in a big volume of liquid.
Using microfluidic devices, we can control the environments around the cell. The cell cell communication, as well as cell soluble factor influence much more precisely than just doing the experiment on a larger scale in a Petri dish. So the, these new developments in micro fluidic brings a lot of promise with control and reproducibility over conventional methods.
Our research in using microfluidic devices for cell migration research involves developing new devices that can maintain a steady gradient of soluble factors over the cells, such that we can study how the cells respond to different growth factors or chemokines. This involves in precise control of fluid flow over a group of cells or cells, which is very important and fundamental in most of the biological processes such as morphogenesis, cancer metastasis, and immune cell response. Similar To those microfluidic devices for generating gradients, the devices for culturing neurons and especially com neurons is a new development in microfluidics.
With these devices, we are able to isolate and purify axonal fractions and also obtain very polarized structures. In this case, compared to conventional assays such as void and chambers, where it was very, it was sometimes difficult to prevent leakage and other experimental difficulties. Micro fluidic devices offer overall more reproducible results and at the same time provide optically compatible platform where we can do high resolution microscopy.
And this device is being used to perform experiments to look at how axonal transport is happening. So using this new microfluidic neuronal culture device, a lot of our collaborators across the country are looking at different neurodegenerative models such as Alzheimer's disease, Parkinson's disease, and A LSI Was very fortunate to have excellent collaborators in the neuroscience and the pathology department here at uc Irvine. I collaborate closely with Car Kaman Stewart and Ed Monki and Lisa Flanagan's lab.
Our collaborations involve in meeting regularly and trying to find out what are the problems that the biologists are facing. And in, in these regular meetings, we find out that although there have been conventional tools available, there are still a lot of app applications where us as biomedical engineers can play a significant role in, in improvement and understanding of this biomedical research. So, for example, our collaboration with Dr.Monki and Dr.Flanagan's lab over the last five years has been very productive.
First, our students can learn how to work closely with, with groups, with different scientific disciplines. And at the same time, we have been fortunate to tackle problems in stem cell biology. For example, culturing and differentiating stem cells within microfluidic devices offered a fresh perspective on how stem cells behave in gradient A morphogen such as BMP.
And I think this type of collaboration will be an important part of future science as more and more engineers get interested in biomedical research. And at the same time the needs for new tools with new capabilities from the neuroscience and other bioscience field grow, I expect that there's gonna be a lot of fruitful collaborations that will really push the field of biomedical research. Further, I Think the field of microfluidics and biomes is an exciting phase.
There are are a lot of new applications that's being developed basically every day. I expect that in five years there will be a lot more biologists using these type of devices for daily research, for routine experiments, for cell migration or other special purposes. Because these devices offer a lot of advantages over conventional Petri culture based methods, I think the imagination is a limit for developing new types of applications.
And I, I believe close collaboration with the biologists will result in new types of devices, which will play significant role in future advancement of biomedical research.
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Overview
Newly John from the University of California Irvine discusses his research in developing novel biomedical and microfluidic devices for neuroscience and stem cell research. This emerging field leverages techniques from the integrated circuit industry to create miniaturized devices for cell biology applications.
Key Study Components
Area of Science
- Biomedical Engineering
- Neuroscience
- Microfluidics
Background
- Microfluidics is a young discipline that has evolved over the past decade.
- It utilizes methods from the integrated circuit industry.
- Traditional biological experiments typically use larger scales, such as Petri dishes.
- Cells are often immersed in large volumes of liquid, which can limit experimental precision.
Purpose of Study
- To develop small devices with channels and reservoirs for cell biology applications.
- To improve the precision of experiments involving small cells.
- To explore the potential of miniaturization in biomedical research.
Methods Used
- Development of novel biomedical devices.
- Application of microfluidic techniques.
- Utilization of miniaturization methods from integrated circuits.
- Experimental design focused on small-scale biological applications.
Main Results
- Creation of devices that can manipulate small volumes of liquid.
- Enhanced ability to conduct experiments on a microscale.
- Potential for improved outcomes in neuroscience and stem cell research.
- Demonstration of the advantages of miniaturized experimental setups.
Conclusions
- Microfluidic devices represent a significant advancement in biological research.
- Miniaturization can lead to more precise and controlled experiments.
- Further development in this area could transform neuroscience and stem cell applications.
Frequently Asked Questions
Executive Industry Relevance
Microfluidic devices enable precise control of cellular microenvironments, addressing a key challenge in neuroscience and stem cell research where conventional Petri dish models lack spatial and temporal resolution. This technology supports mechanistic de-risking by allowing fluidic isolation of axonal and somal compartments, facilitating targeted insult studies and pure fraction collection for downstream analysis. The platform enhances predictive confidence in target validation and assay development by improving reproducibility and enabling high-resolution live-cell imaging.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses through fluidic isolation of neuronal compartments to study compartment-specific responses to soluble insults.
- Operational Value: Supports functional target validation by maintaining polarized neuronal structures for up to 2-3 weeks, allowing longitudinal assessment of axonal transport and degeneration.
- Predictive Value: Improves confidence in target engagement studies by reducing experimental variability through precise microenvironment control and reproducible fluidic gradients.
Screening & Assay Development
- Scientific Value: Provides a standardized platform for preparing validated biological systems with fluidic separation, enabling reliable compound screening in distinct axonal or somal compartments.
- Operational Value: Enhances assay reproducibility and scalability through precision-molded polymer parts and compatibility with DIC, phase contrast, confocal, and two-photon microscopy.
- Platform Utility: Supports downstream biochemical analysis such as PCR on pure axonal fractions, increasing screening readiness for target and pathway elucidation.
Translational & Preclinical Research
- Translational Relevance: Models CNS injury and neurodegeneration by enabling localized delivery of toxicants or aggregates to axonal compartments for up to 20 hours post-medium change.
- Preclinical Continuity: Bridges discovery and preclinical validation by allowing longitudinal culture and fixed-endpoint immunocytochemistry to assess structural and functional outcomes.
- Risk-Adjusted Advancement: Informs go/no-go decisions by providing quantitative, compartment-specific readouts that reduce mechanistic ambiguity in target pathways.
Pipeline & Workflow Integration
The microfluidic neuronal culture platform integrates into the discovery continuum from hypothesis testing through lead identification to preclinical validation, supporting iterative design-test cycles in neurotherapeutic development.
- Discovery Biology: Supports hypothesis testing by enabling precise spatiotemporal control of soluble factor gradients to study chemotaxis, morphogenesis, and immune cell responses in a reductionist format.
- Screening: Delivers assay readiness through optically compatible, fluidically isolated compartments that allow parallel compound evaluation without cross-contamination.
- Analytics: Generates quantitative dependent variable measurements such as axonal fluorescence intensity, transport velocity, and PCR-based molecular profiles from purified fractions.
- Translational Research: Connects to preclinical workflows by modeling CNS pathology mechanisms like axonal degeneration and transport deficits relevant to Alzheimer’s and Parkinson’s disease.
- Enterprise Reuse: Functions as a reusable platform across projects due to its adaptability to various neuronal types, stem cell derivatives, and soluble factor assays.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in target validation by reducing biological noise and enabling mechanistic de-risking through compartment-specific perturbation.
- Operational Value: Delivers standardization and reproducibility via precision molding and fluidic control, minimizing well-to-well and experiment-to-experiment variability.
- Strategic Value: Improves capital efficiency by reducing false positives in early screening and decreasing late-stage attrition due to better biological fidelity.
- Portfolio Impact: Enables risk-adjusted prioritization of neurotherapeutic candidates through compartment-resolved efficacy and toxicity profiling.
Implementation Considerations
- Requires expertise in microfluidic design, neuronal culture, and live-cell imaging to optimize device fabrication and experimental setup.
- Depends on access to microfluidic fabrication tools, pressure control systems for hydrostatic isolation, and compatible microscopy platforms.
- Necessitates cross-team standardization between engineering and biology teams for consistent device operation and data interpretation.
- Involves adaptation considerations when extending beyond CNS neurons to other cell types, such as stem cells or immune cells, due to differing adhesion and migration properties.
- Limited by the need for aseptic technique and medium change protocols to maintain fluidic isolation over extended culture periods (2-3 weeks).
