Development of New Therapeutic Applications Using Microfluidics

My name is Mamed Toner. I'm a trained in mechanical engineering originally and biomedical engineering and sciences afterwards. And I'm a faculty member at the Massachusetts General Hospital, Harvard Medical School, and Harvard, MIT, division of Health Sciences and Technology in exploring various applications of biomedical engineering in medicine, various from finding common cells in blood that can be, you can determine, find them very rapidly changing their physiology so you can understand the physiology of these cells in a disease state, let's say in inflammation or a burn or injured patient.

And trying to understand the innate immune system response and trying to understand how blood cells regulate the inflammatory response in these kind of cases and, and looking at their genomics and proteomics. In those kind of examples, what you want to do is say you like to find these cells without altering their physiology and expression levels and so and so forth. So what you're investigating is the natural physiology of the underlying problem and not an artifact of handling the cells.

Other applications will be point of care type devices such as in global health chips that could measure cells of interest that will determine therapy initiation such as the level of CD four positive lymphocytes. And so we are working on developing chips that could find and count the CD four positive cells in a, on a microfluidic microchip technology and more complicated applications will be in what we call rare cell detection. It is in medicine, clinical medicine, we usually deal with common cells and try to understand the person's physiology based on those cells.

But in reality, many of the physiological or pathophysiological processes are controlled by much more, much less common cells, such as dendritic cells, stem cells, and regulatory cells, or in the case of cancer, circulating tumor cells. So we have interest in finding rare cells that actually determine the response to various treatments as well as could be used as diagnostic. So it's a very broad aspect of using microfluidics and moving, putting cells on chips for a number of diagnostic and therapeutic applications there.

Early studies in microfluidics were primarily focused on building, benefiting from the tools of microsystems technologies develop for integrated circuit type applications and applying miniaturizing systems for labon chip type concepts where one would develop developing micro flow cytometry, micro electrophoresis systems, micro chromatography systems. And from these miniaturization studies we've learned a lot about how to bring biological systems together with microsystems. And what has been missing in the field so far is major applications, successful applications where we call it blockbusters or big clinical impact applications of these technologies.

So our laboratories, especially being in a major research hospital, is focused on exploring meaningful, enabling applications of these technologies and come up with areas where we can solve problems that couldn't be solved otherwise. For example, in the case of AIDS for a global health application, a chip that is very inexpensive, that can be used to find and can't see the for disposable chip find and can't see the for positive lymphocytes from whole blood, from a finger prick of blood and which has point of care features. And it will be this technology if success will be used by millions of people.

So manufacturing these things, scaling it up and using it at high impact applications where we have focused our attention as well as many others in the field lately. But there's where I see there's gonna be major advances in the field in finding the meaningful application of these technologies in clinical medicine and biological sciences, the same tools are also explored in, in very clever ways to address fundamental biological processes such as investigate cell cell interactions, investigate how cells respond to environmental cues, controlling microenvironment of the cells and tissues very precisely, that can then be used to understand the form fundamental processes that regulate the bio biological response. The applications of this in like living salary type concepts that we are working on where cells will be labeled clones of cells with that will report on different genes that could be put in a, are put in a very complex microfluidic network and exposed to thousands of different conditions in one experiment.

And you can monitor the real time gene expression of these cells that are tagged with spec, different clones tagged with different genes. Critical issues is one of the biggest issues in the field in my view, is to how to translate these. Some of the basic science findings or these cool technologies, so to speak into new therapies or meaningful biological applications is it's a very multidisciplinary field.

You need engineers, you need physicists, you need biologists, neurobiologists, depending on the applications. So bridging the disciplines is, in my view has been one of the biggest issues. Most of the early discoveries were done by engineers and physicists with no good training or understanding of the biological problems.

But more recently biologists also are finding this, these tools, very ex exciting difference between these different disciplines are being closed significantly over the recent years because the interest in both on the biology side as well as the multidisciplinary pupils such as our group are exploring these applications of these tools and clinical medicine and biology. To me that's one of the multidisciplinary aspect is one of the major issues that is impacting the translation of these ideas. The other one is the bridge between academia and industry.

Many of these ideas are generated in academia, but they're very complex and they involve cells, they involve complex biological processes and then they also involve complex engineering, manufacturing, packaging issues. And so the translation of commercialization of these technologies is something that needs a tremendous attention. Some of that load is in, is on the shoulders of industry.

How do you take fundamental breakthroughs in the industry is not as straightforward process, especially when it involves clinical studies and biological samples. So to those two issues, the multidisciplinary nature of the field and translation from academia to industry might be are the two major hurdles that we need to tackle in the years ahead. But there are a lot of groups working on these issues and, and I see quite an exciting future for the applications of what I call tiny technologies, micro and nano technologies in medicine and biology.