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ILP Institute Insider

June 13, 2013

Making Waves with Microfluidics

Joel Voldman engineers cutting-edge approaches to stem cell signaling, point of care therapeutics, and neuroengineering.

Alice McCarthy

In the never-ending mega study of how biological systems work, Joel Voldman’s mission is to understand the most basic interactions between single cells. To achieve that, he applies the power of microfluidics to isolate the actions and behaviors of single cells and the interactions between cells.

Joel Voldman
Associate Professor, Electrical Engineering
Co-Director, MEDRC
Cells are small—most on the order of 1-20 microns—and the science of microfluidics allows researchers to develop devices commensurate with that size. “Specifically, we want to enhance or enable the acquisition of information from cells, to understand and control what cells do, and we use microfluidic systems to do that,” Voldman explains. “This research sheds light on how cells work and will hopefully have a direct impact on medicine.”

Stem Cell Signaling
One of Voldman’s main projects is the study of stem cells, those cells capable of transforming into several different cells types in the body. Stem cells can remain as stem cells in a process known as self-renewal or they can evolve into another cell type. If you can control those decisions, you could potentially cause those stem cells to turn into important tissues for use in regenerative medicine or testing drug toxicology.

Although the science of stem cell biology has made terrific strides in the past 30 years, since the first mouse embryonic stem cells were isolated and since the derivation of human stem cells in 1998, researchers have largely been unsure what specific factors are responsible for that cellular metamorphosis. That recipe is controlled by interactions between the cells. And the fate of the cell is controlled locally in the size range of hundreds of microns.

“Because we can manipulate things in that size range using microfluidics, we can start to do experiments that illuminate how those decisions are made and then potentially control those,” adds Voldman.

Voldman’s group recently applied the science of microfluidics to study how stem cells communicate with each other in media that influence their outcome. They secrete molecules into the liquid that diffuse and interact with the cells around them. These processes are hard to study and control, however. But Voldman and colleagues developed novel microfluidic systems that allow them to control the environment around the cells very precisely.

“We can turn those signals on and off and for the first time we could show how removing those signaling molecules influences the fates of those cells,” he explains.

Specifically, his research group discovered that an important class of signaling molecules, known as matrix metalloproteinases (MMPs), keeps embryonic stem cells stable and consistent over time and ready for transformation. Until Voldman’s research, the role of MMPs in stem biology was underappreciated.

There are potentially important medical reasons to keep stem cells stable: to exponentially create a large homogeneous stem cell population on an industrial scale. For transplantation or any sort of therapy, billions of stem cells might be needed. “The methods to create stem cells populations have been available but the recipe was not completely known,” Voldman adds. “We’ve identified this critical element to the recipe. Now others can pose their own questions of these cells and apply these technologies to these cells.”

Medical Devices on the Micro Scale
Through his involvement with the Medical Device Realization Center (MEDRC) at MIT, Voldman is collaborating with several different research industries including those in microelectronics, medical devices, pharmaceuticals and biotech to radically advance the field of medical device development. Following the example set by the microelectronics industry in the radical transformation in computers and cell phone innovation, the MEDRC seeks to bring similar substantial innovation to medical devices.

Although the Boston/Cambridge area is home to extremely deep biomedical science know-how, the MEDRC is seeking to fill an important gap. “There are many technologies that are almost good enough but not quite right for the next-generation of medical devices,” explains Voldman. “We can identify and fill that gap,” he says. “We may see a medical need and possible technical solutions for that need. If brought to us at MIT we can de-risk a technology enough so that it can be commercialized by a company.”

Through the MEDRC, Voldman is particularly interested in developing new point of care medical devices incorporating microfluidics technology. Envision blood work analysis that requires only a finger prick 15 minutes before a scheduled doctor appointment where results are made available immediately for discussion rather than having to get a call back and another visit.

Collaborating scientists and engineers from industry take up residence at the MEDRC to work on a given project. That tight relationship with industrial partners and the end user and the physician is in the DNA of how these projects work. Not only does this type of collaboration allow the project to stay focused and relevant to the sponsoring company but it also prevents development of a technology that is not commercially viable. “This type of research approach is valuable to our industry partners,” Voldman says. The visiting scientist knows what is going on behind the firewall at their company and they are able to take the science learned from the open MIT environment back to the company.

Voldman adds, “From our point of view, it increases the likelihood that what we develop will reach commercialization and change how medicine is done.”

Neuroengineering
Voldman’s research team also participates in the National Science Foundation’s Center for Sensorimotor Neural Engineering (CSNE). For this initiative, his team is focused on developing new technologies that can sense information from neurons. Like cells, neurons are bathed in fluid which is why Voldman believes that much of what he knows about microfluidics can be directly applicable to the study of neurons.

“We are working with colleagues to make neural recordings from electrodes implanted next to neurons,” explains Voldman. “These electrodes can ‘hear’ the electrical firing of the neuron and infer what is going on.” Targeted applications may include the ability to reanimate a paralyzed limb or control a prosthetic. One of the major challenges in the field of neuroengineering is maintaining active implantable electrodes in the brain over a long period of time. His team is working on strategies to ensure the long-term viability of these electrodes.

Regardless of the applications, Voldman asserts that MIT is the best place to do microfluidics research applied to biology and medicine. Acknowledging MIT’s surrounding unparalleled biomedical enterprise, its world-class activities in all areas of microfluidics research, and the strengths of its professors, postdocs, and students, Voldman sees another key strength. “MIT has an ease and familiarity with industrialization and with industrial connections,” he explains. “There are processes for working with both startups and established companies so you can translate your discoveries out in to the marketplace.”