A PDMS microfluidic device for generation and dilution of two-dimensional combinatorial solution mixtures, integrated with a well array for cell storage and culture from the Khademhosseini lab at Harvard Medical School. See: http://pubs.rsc.org/en/content/articlelanding/2011/lc/c1lc20449a
Microfluidics could enable fundamentally new measurements at the cell/tissue level (not just faster, cheaper, or miniaturized versions of existing assays). In industry, this relates to what Fluidigm, CellAsic, and others are already doing.
“Dr. Manz believes there is growing interest and research on the use of microfluidic devices for cell-based studies. In contrast to the molecular diagnostics arena—in which “I have seen little that is revolutionary about microfluidics in the sense of obtaining fundamentally new information,” Dr. Manz points to new work from the fields of cell biology and tissue engineering.
Expiration of patents may encourage commercial development: Manz argues that the expiration of key microfluidics patents should free up the commercialization process.
Move toward easier-to-use systems: One form of this is the rise of simpler, paper-based, readerless chips (e.g., Diagnostics for All, Paul Yager’s initiatives). Others are developing systems with all sensing and control integrated into a single, easier-to-use device.
The orientation, size, geometry, layout, and pitch of microfluidic ports has many variations. Establishing a standard in this area will allow for lower cost, greater automation, improved compatibility, and minimizing re-engineering.
Following their recent acquisition by Opko, Claros Diagnostics is hiring! There are two exciting openings for Project Leaders in Assay Development, as they are expanding the development of new assays on their platform.
This is a terrific opportunity for industry veterans or qualified individuals looking to enter industry. Check them out here and here at the job board!
Great to see ~50 new and familiar faces from the Boston/New England lab-on-a-chip community gathered the first FluidicMEMS event this fall on November 14th at MIT! Thanks to extraordinary co-organizers A.J. Kumar and Joost Bonsen. We were generously sponsored by the MIT Alumni Association (thanks Katie Mahoney!) and Zeta Instruments.
This time I shared some thoughts on commercialization, and many interesting and intense discussions were had by all. We’ve got some exciting events planned for the winter and spring, so drop us a line if you’re interested in hearing about future events.
Quick video of Patrick Beattie from Diagnostics for All explaining how they’re using low-cost paper microfluidics to save lives at birth in the developing world. Specifically, DFA is developing a test for anemia and hyper/hypoglycemia, and a test for proteinuria to detect preeclampsia.
See other innovators working on saving lives at birth here and here.
Last week we heard more from Eileen Bartholomew of the XPRIZE Foundation about the anticipated 2012 announcement of the Tricorder XPRIZE. Named after the universal medical diagnostic from Star Trek, the device should allow consumers to diagnose themselves, enabling people to become “CEOs of their own health.” There’s a huge potential for microfluidics to be involved with a point-of-care device like this, especially since lab-on-a-chip systems could facilitate ease-of-use and require smaller sample volumes (e.g., a fingerprick of blood vs. a vial of blood that would need to be drawn by a professional).
Specs so far:
Usable by consumers without aid from medical professionals
Single device with the ability to diagnose 15 diseases: 12 core-set diseases + 3 elective-set diseases. Examples: Hypertension, urinary tract infection, sleep apnea, sexually transmitted illness (STI)
Diagnostic results within 3 days
Probably linked to a mobile device like a smartphone (note the contest is being underwritten by Qualcomm)
Expected prize announcement in 2012
Duration of competition expected to be ~ 3.5 years long
Will the XPRIZE motivate existing companies to collaborate? Currently many are struggling to launch a test that outputs one or two results, never mind 15. I also wonder how the 15 diseases chosen will affect marketing for the device. What if you’re a relatively healthy person who only needs 3 out of the 15 functions? Would you pay more for an all-in-one device like this, or are you more likely to buy individual tests based on your needs? How much use will be symptom-driven (urinary tract infection) vs. long-term monitoring of a known condition (hypertension) vs. screening (STIs)?
Recently I ran across this Stanford video of Gajus Worthington, co-founder and CEO of Fluidigm. Recorded in 2004, it’s a behind-the-scenes snapshot of the early years of the company, after they’d launched their first products (in protein crystallization) in 2003. Over the past decade Fluidigm has gone from fundraising to becoming a public company with a 2010 revenue of $33.6 million.
One quote grabbed me:
“We did this wrong, if you read the textbooks. You’re supposed to figure out what the market opportunity is, then you’re supposed to go out and find technology, and build a team, and all that kind of stuff. Right. We didn’t do it that way.
We did it, classically, the way you’re not supposed to, which is you find a technology, you get obsessed with it, and you go running around trying to figure out what can I do with it. Well I submit to you that that’s the way most technology companies work.
That’s the way it worked with the laser, that’s the way with lots of other components. You have some kind of technology, you get a bunch of smart people who are obsessed with it. And ultimately they find something useful they can do with it. It’d be nice to do it the other way, but unfortunately I really don’t know of any examples where that has transpired. ” — Gajus Worthington, CEO of Fluidigm
I tried thinking of biomedical technology companies that started with a market opportunity first, and then developed solutions. I couldn’t come up with any in the microfluidics space. (Although it is hard to know the backstory behind how companies match product and market.) Do you have any examples of a team starting with a problem, evaluating a range of solutions (microfluidic and non-microfluidic), choosing to go with microfluidics, and then building a microfluidics team?
In diffusible signaling, cells communicate with each other by secreting signaling molecules which diffuse into the surrounding liquid before being taken up by those same cells or neighboring cells via receptors. Cell signaling is especially important for stem cells because it can determine how a stem cell specializes into various tissue types. Traditionally cells are grown in Petri dishes in standing liquid. In these conditions, the chemical makeup of the environment around the cells is constantly changing as cells secrete and take up a complex array of signaling molecules. It has been challenging for biologists to experimentally probe the details of these closed-loop interactions: what molecules are secreted when, which cells receive the signals, and what effects do the signals have on the cell?
Enter microfluidics. This paper shows how microfluidics provide a new tool for biologists to interrogate diffusible signaling loops. The idea: for cells grown under continuous, non-recirculating microfluidic perfusion, most secreted signaling molecules are swept away before binding to nearby cells. This continuous clearing enables more strict control over the cell’s environment by allowing the researcher to specify what molecules are perfused into the cell culture. In engineering terms, you have more control over the inputs (signaling molecules) to the system (the cell).
Not only did Katarina show that continuous flow can disrupt diffusible signaling, she was able to uncover a specific biological result which suggests that FGF4 is not the only cell-secreted molecule needed for differentiation of the stem cells to neuroectoderm (cells that gives rise to our nervous system during development).
Blagovic, K., Kim, L. Y., Skelley, A. M., & Voldman, J., “Microfluidic control of stem cell diffusible signaling,” Micro Total Analysis Systems ’08 677-679, 2008. | Downoad PDF
K. Blagovic, S. P. Desai, and J. Voldman, “Micro-patterned polystyrene substrates for highly integrated microfluidic cell culture ” in Micro Total Analysis Systems 2009, Jeju, Korea, 2009, pp. 144-6. | Download PDF
Fantastic to hear about a new, substantial U.S. government funding effort in microfluidics research! Last month a joint effort between the NIH, DARPA, and the FDA was announced to develop human-on-chip platforms to test drug candidates more efficiently and accurately. The NIH and DARPA are soliciting proposals separately from all types of research organizations (academic, industry, government, other) and each agency plans to commit up to $70 million to the effort (up to $140 million combined).
A big problem in drug development is that current methods for testing safety and efficacy are either cheap and inaccurate (in vitro experiments, animal studies) or more accurate and very expensive (human clinical trials cost $20k – $50k per patient). Often a drug works in a mouse but doesn’t work in humans, leading to millions lost on failed clinical trials. The hope is that microphysiological environments mimicking human tissue and organ structure may enable more accurate assessment of a drug’s performance at much lower cost. These chips wouldn’t replace clinical trials, but might allow us to hone in on effective drugs earlier in the development process, saving time and money.
DARPA has already begun soliciting proposals, and abstracts are due in just a few days (Oct 27, 2011). Full proposals are due on Dec 12, 2011. To apply, see more information here and here. There’s also a teaming website here to help facilitate collaboration. From the DARPA website:
DARPA is soliciting innovative research proposals to develop an in vitro platform of human tissue constructs that accurately predicts the safety, efficacy, and pharmacokinetics of drug/vaccine candidates prior to their first use in man. Alternative testing methods that rely on isolated human cells hold the promise of authentic human responses to candidate drugs, vaccines, and biologics. Recent research has shown that three-dimensional constructs of one or more cell types are able to reproduce relatively authentic human tissue and organ physiology in an in vitro environment. As a result, DARPA seeks in vitro platforms comprised of human tissue constructs that will accurately assess efficacy, toxicity, and pharmacokinetics in a way that is relevant to humans and suitable for regulatory review.
a blog about microfluidics and bioMEMS technologies and how they can help solve real-world problems. Written by Lily Kim, a biomedical-engineer-turned-technology-strategist, FluidicMEMS covers new developments fresh from academia as well as the process of bringing these technologies into the world.