Light switch for Neurons

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Moving microfluidics from the lab bench to the factory floor

As the United States seeks to reinvigorate its job market and move past economic recession, MIT News examines manufacturing’s role in the country’s economic future through this series on work at the Institute around manufacturing.

 

ImageThe Center for Polymer Microfabrication is designing processes for manufacturing microfluidic chips. Pictured here is a chip fabricated by the center’s tailor-made production machines.
Photo: Melinda Hale

In the not-too-distant future, plastic chips the size of flash cards may quickly and accurately diagnose diseases such as AIDS and cancer, as well as detect toxins and pathogens in the environment. Such lab-on-a-chip technology — known as microfluidics — works by flowing fluid such as blood through microscopic channels etched into a polymer’s surface. Scientists have devised ways to manipulate the flow at micro- and nanoscales to detect certain molecules or markers that signal disease.

Microfluidic devices have the potential to be fast, cheap and portable diagnostic tools. But for the most part, the technology hasn’t yet made it to the marketplace. While scientists have made successful prototypes in the laboratory, microfluidic devices — particularly for clinical use — have yet to be manufactured on a wider scale.

MIT’s David Hardt is working to move microfluidics from the lab to the factory. Hardt heads the Center for Polymer Microfabrication — a multidisciplinary research group funded by the Singapore-MIT Alliance — which is designing manufacturing processes for microfluidics from the ground up. The group is analyzing the behavior of polymers under factory conditions, building new tools and machines to make polymer-based chips at production levels, and designing quality-control processes to check a chip’s integrity at submicron scales — all while minimizing the cost of manufacturing.

“These are devices that people want to make by the millions, for a few pennies each,” says Hardt, the Ralph E. and Eloise F. Cross Professor of Mechanical Engineering at MIT. “The material cost is close to zero, there’s not enough plastic here to send a bill for. So you have to get the manufacturing cost down.”

Micromachines

Hardt and his colleagues found that in making microfluidic chips, many research groups and startups have adopted equipment mainly from the semiconductor industry. Hardt says this equipment — such as nano-indenting and bonding machines — is incredibly expensive, and was never designed to work on polymer-based materials. Instead, Hardt’s team looked for ways to design cheaper equipment that’s better suited to work with polymers.

The group focused on an imprinting technique called microembossing, in which a polymer is heated, then stamped with a pattern of tiny channels. In experiments with existing machines, the researchers discovered a flaw in the embossing process: When they tried to disengage the stamping tool from the cooled chip, much of the plastic ripped out with it.

To prevent embossing failures in a manufacturing setting, the team studied the interactions between the cooling polymer and the embossing tool, measuring the mechanical forces between the two. The researchers then used the measurements to build embossing machines specifically designed to minimize polymer “stickiness.” In experiments, the group found that the machines fabricated chips quickly and accurately, “at very low cost,” Hardt says. “In many cases it makes sense to build your own equipment for the task at hand,” he adds.

In addition to building microfluidic equipment, Hardt and his team are coming up with innovative quality-control techniques. Unlike automobile parts on an assembly line that can be quickly inspected with the naked eye, microfluidic chips carry tiny features, some of which can only be seen with a high-resolution microscope. Checking every feature on even one chip is a time-intensive exercise.

Hardt and his colleagues came up with a fast and reliable way to gauge the “health” of a chip’s production process. Instead of checking whether every channel on a chip has been embossed, the group added an extra feature — a tiny X — to the chip pattern. They designed the feature to be more difficult to emboss than the rest of the chip. Hardt says how sharply the X is stamped is a good indication of whether the rest of the chip has been rendered accurately. 

Jumpstarting an industry

The group’s ultimate goal is to change how manufacturing is done. Typically, an industry builds up its production processes gradually, making adjustments and improvements over time. Hardt says the semiconductor industry is a prime example of manufacturing’s iterative process.

“Now what they do in manufacturing is impossibly difficult, but it’s been a series of small incremental improvements over years,” Hardt says. “We’re trying to jumpstart that and not wait until industry identifies all these problems when they’re trying to make a product.”

The group is now investigating ways to design a “self-correcting factory” in which products are automatically tested. If the product doesn’t work, Hardt envisions the manufacturing process changing in response, adjusting settings on machines to correct the process. For example, the team is looking for ways to evaluate how fluid flows through a manufactured chip. The point at which two fluids mix within a chip should be exactly the same in every chip produced. If that mixing point drifts from chip to chip, Hardt and his colleagues have developed algorithms that adjust equipment to correct the drift.

Holger Becker, co-founder of Microfluidic ChipShop, a lab-on-a-chip production company in Jena, Germany, says the center’s research plays an important role in understanding the different processes involved in large-scale production of microfluidics.

“Most of the academic work in microfluidics concentrates on applications, and unfortunately only very few concentrate on the actual manufacturing technologies suited for industrialization,” Becker says. “David Hardt’s team takes a very holistic approach looking into all different process steps and the complete manufacturing process instead of individual technologies.”

“We’re at the stage where we’d like industry to know what we’re doing,” Hardt says. “We’ve been sort of laboring in the vineyard for years, and now we have this base, and it could get to the point where we’re ahead of the group.”

By MIT News

Institute faculty share prestigious neuroscience prize Ed Boyden and Feng Zhang awarded the Perl/UNC Neuroscience Prize

MIT faculty members Ed Boyden and Feng Zhang, along with Karl Deisseroth of Stanford University, have been awarded the Perl/UNC Neuroscience Prize for developing a way to control brain activity using light. The Perl prize carries a $10,000 award and is given annually to recognize a seminal achievement in neuroscience. Four of the 12 past recipients were later awarded Nobel Prizes.

Boyden, Zhang and Deisseroth share the 2012 Perl prize for developing a technology known as “optogenetics,” in which neurons are genetically engineered to respond to light. This allows researchers to control the activity of specific cell types with great precision, and to probe the brain’s intricate circuits in ways that would have been unimaginable a few years ago. Optogenetics has already led to major advances in basic neuroscience, and the method has great promise for understanding and potentially for treating a wide range of brain disorders.

Boyden is a faculty member in the MIT Media Lab and an investigator at the McGovern Institute for Brain Research. Zhang is also a McGovern Investigator, with a joint appointment in the Department of Brain and Cognitive Sciences and at the Broad Institute.

Zhang and Boyden will deliver their prize lectures at the University of North Carolina at Chapel Hill on Sept. 20.

By MIT news

A pulsating gut on a chip

A coin-sized device created by a team at Harvard University mimics the structure and physiology of the human intestine by supporting gut microbes and imitating the organ’s rhythmic motion.

Donald Ingber and his colleagues at the Wyss Institute in Boston, Massachusetts, built the chip (pictured) out of a clear polymer. It contains two microscopic fluid channels separated by a porous, flexible membrane. Human gut epithelial cells, which line the gut’s surface, cover the membrane and supported the growth of a common gut bacterium, Lactobacillus rhamnosus. The researchers simulated gut contractions, or peristalsis, by applying suction through two side chambers. In response, the epithelial cells formed folds similar to the finger-like protrusions, or villi, that line the inner intestinal wall.

The gut tissue layer blocked the flow of small molecules between the channels, and this barrier function improved with the presence of the bacteria. The authors say that their device is a better intestinal mimic than cells in static culture and suggest that it could be used for drug screening and toxicity tests.

R. SOC. CHEM.

 

Nature 483, 376 (22 March 2012) doi:10.1038/483376a

Lab Chip 10.1039/C2LC40074J (2012)