Ann Arbor: A gravity-powered chip that can mimic a human heartbeat outside the body could advance pharmaceutical testing and open new possibilities in cell culture because it can mimic fundamental physical rhythms, according to the University of Michigan researchers who developed it. The apparatus is a new development in the "lab on a chip" category—a class of microfluidic devices that can perform complex laboratory functions in a tiny space.
The first uses are likely to be in testing new cardiovascular drugs
and blood thinners, where blood flow is critical to predicting
performance, says Shuichi Takayama, U-M professor of biomedical
engineering and macromolecular science and engineering who is one of the
creators of the device.
"This chip gives us a bridge between the petri dish and the patient,"
Takayama said. "Cells behave much more naturally when they're subjected
to the pulsing rhythms inside the body, as opposed to sitting in a
static environment in the lab. So, by duplicating those rhythms on a
chip, we can perform much more accurate lab tests before we begin
testing on patients."
While previous devices have been able to recreate the pulse of a
heartbeat outside the body, they required the use of a syringe pump
operated by a lab technician, which made long-term tests difficult. The
new device is much simpler to operate and can run unattended for long
periods of time.
The steady input pressure also makes it possible to run multiple
pulse rates and pressures on a single chip. This is a big step forward
because it enables technicians to run multiple tests at once, Takayama
"Different types of patients have different pulse rates," he said.
"For example, a septic patient's heart may beat faster or one blood
vessel may have a different flow rate than another. Those factors
influence how a given therapy will affect a cell. We can now replicate
those factors and many others on a single chip and run the tests
Developed at the Biointerfaces Institute and Michigan Center for
Integrative Research in Critical Care, the chip uses an intricate
network of microscopic, gravity-driven channels, capacitors and switches
to make liquids flow across it in an unlimited variety of pulses and
flow rates. It enables researchers to test new therapies on human cell
samples that have been injected into the device, in an environment that
closely mimics conditions inside the body.
Takayama says the chip can also be used to duplicate other biorhythms
in the body, like signals within the brain and hormone delivery.
"For example, we generally study liver cells' response to insulin by
giving them a big dose all at once," he said. "But in the body, the
liver gets insulin from the pancreas in a series of tiny pulses. We
could use this chip to duplicate those pulses and create a much more
accurate model of what's happening in the body."
chip operates much like an electronic processor in a computer, but it
uses fluid instead of electricity. Sung-Jin Kim, a former researcher in
Takayama's lab who is now an assistant professor of mechanical
engineering at KonKuk University in Seoul, South Korea, explains that
developing switches and capacitors that use fluid is simple in principle
but was difficult to put into practice.
"One of our biggest challenges was building a gravity-driven
microfluidic circuit that works reliably," he said. "Because unlike
electronics, microfluidic switches need negative pressure to close
properly. We eventually realized that we could control the pressure of
the system by positioning the outflow well at a measured distance below
the chip, creating just the right amount of pressure."
The team uses CAD-design software to custom-design each chip to exact
specifications, then uses a combination of soft lithography and
photolithography to mold the chip out of silicon rubber at a cost of
only a few cents each.
Because the chips are used in the lab and not on humans, Kim says
researchers can begin using them right away. He says the team has no
immediate plans for commercialization, but they may begin sharing the
design with researchers on a noncommercial basis in a matter of months.
The team's findings are detailed in a study published in Nature
Communications, titled "Multiple independent autonomous hydraulic
oscillators driven by a common gravity head." Funding was provided by
the National Institutes of Health (grant no. 096040), Institutional
Program for Young Researcher Overseas Visits of Japan and the National
Research Foundation of Korea.