David Beebe, Biomedical Engineering Associate Professor at the University of Wisconsin-Madison, has created palm-sized “laboratories” that require no assembly, contain no electronics and are powerful enough to detect botulinum neurotoxin in a tiny drop of blood. In addition, he can fabricate them in about an hour to perform several assay steps.
With approximately $7 million in Defence Advanced Research Projects Agency funding over the last six years, Beebe has studied microfluidic systems. His latest advance, published in the journals Analytical Chemistry and Electrophoresis, details the method his research group developed for making customised integrated microsystems easily and quickly.
The traditional time-consuming, labour-intensive solid-phase process includes liquid, solid, light-exposure, etching and removal steps. But Beebe’s method hinges on using a liquid-phase processing technique to make the devices in situ.
Researchers start with polycarbonate top and bottom layers, which they bond with an adhesive gasket, leaving a gap of 100 to 200 microns. Then they fill the gap with a photo-polymerisable polymer. Using masks, they shine light on selective areas of the device to form a channel network, then remove the excess polymer. They can make multiple layers and, to add pumps, filters, valves and other components, flow a different polymer into the channels and repeat the process.
With University of Illinois Urbana-Champaign Chemistry Professor Jeff Moore, the group was first to incorporate materials that respond to environmental stimuli such as temperature, light, pH or a biological agent and react according to conditions in the channel. “There’s no external power required,” says Beebe. “All of the power comes directly from chemical-to-mechanical conversion.”
Building the devices, which are easily customised for many applications, doesn’t require a clean room. Although Beebe’s group collaborated with Food Microbiology and Toxicology Professor Eric Johnson to develop a system specifically to detect the botulinum neurotoxin, the applications are far-reaching.
His group is currently working with Pediatrics Professor Michael MacDonald on a microfluidic insulin delivery patch so that parents don’t need to wake diabetic children at night to give them shots. Rather, they’d just apply the patch, which would deliver an appropriate overnight dose.
Beebe’s goal is to improve upon it as well: “This whole idea of using stimuli-responsive organic materials should allow us to make a similar low-cost patch that senses the glucose level and regulates the release in response to changes,” he says.
The holy grail of drug delivery is that ability to monitor the body in real time and adjust dosage and delivery accordingly. According to Beebe, that goal is within reach, although appropriate chemistries still need to be developed to make the goal of low-cost, responsive drug delivery a reality. “From the engineering side, we really have demonstrated all of the functionality necessary to do the closed-loop system,” he says, about his devices’ ability to sense and react to environmental changes.
His research group is also focusing on building microsystems to study basic cell biology. Beebe’s students, as well as staff at his company, Vitae, have researched embryos, cell biology and microsystems for several years and soon hope to release a product for human in-vitro fertilisation. “What we’ve shown is that by culturing embryos in a microfluidic environment, you can modify their behaviour,” he says. “And in the case of mice embryos and other tests that are ongoing, they actually are ‘happier’ and behave more like they do in vivo.”
With funding from the Army, the group plans to extend the concept to mammary gland progenitor cells for breast-cancer research in collaboration with Oncology and Biomedical Engineering Assistant Professor Caroline Alexander. In addition, Beebe will use a recently awarded UW-Madison industrial and economic development research technology transfer grant to develop systems for drug discovery with BellBrook Labs, a Madison-based biotechnology company.