Marrying high performance optics with microfluidics

Harvard engineers have successfully created a silicone rubber stick-on sheet containing dozens of miniature, powerful lenses, bring them one step closer to putting the capacity of a large
laboratory into a micro-sized package.

The marriage of high performance optics with microfluidics could prove the perfect match for making lab-on-a-chip technologies more practical.

Microfluidics, the ability to manipulate tiny volumes of liquid, is at
the heart of many lab-on-a-chip devices. Such platforms can
automatically mix and filter chemicals, making them ideal for disease
detection and environmental sensing.

The performance of these devices, however, is typically inferior to
larger scale laboratory equipment. While lab-on-a-chip systems can
deliver and manipulate millions of liquid drops, there is not an equally
scalable and efficient way to detect the activity, such as biological
reactions, within the drops.

The Harvard team’s zone-plate array optical detection system, described
in an article appearing in the journal Lab on a Chip, may offer a
solution. The array, which integrates directly into a massively parallel
microfluidic device, can analyze nearly 200,000 droplets per second; is
scalable and reusable; and can be readily customized.

“In essence, we’ve integrated some high performance optics onto a chip
that contains microfluidics as well. This allows us to be able to
parallelize the optics in the same way that a microfluidic device
parallelizes sample manipulation and delivery,” says Ken Crozier, an associate professor of electrical engineering at Harvard’s School of
Engineering and Applied Sciences (SEAS), who directed the research.

Unlike a typical optical detection system that uses a microscope
objective lens to scan a single laser spot over a microfluidic channel,
the team’s zone-plate array is designed to detect light from multiple
channels simultaneously. In their demonstration, a 62 element zone-plate
array measured a fluorescence signal from drops traveling down 62
channels of a highly parallel microfluidic device.

The device works by creating a focused excitation spot inside each
channel in the array and then collects the resulting fluorescence
emission from water drops traveling through the channels, literally
taking stop-motion pictures of the drops as they pass.

“Water drops flow through each channel of the device at a rate of
several thousand per second,” explains lead author Ethan Schonbrun, a
graduate student at SEAS. “Each channel is monitored by a single zone
plate that both excites and collects fluorescence from the high speed
drops. By using large arrays of microfluidic channels and zone plate
lenses, we can speed up microfluidic measurements.”

The series of images are then recorded by a digital semiconductor (CMOS)
camera, allowing high speed observation of all the channels
simultaneously. Moreover, the array is designed so that each zone plate
collects fluorescence from a well-defined region of the channel, thereby
avoiding cross talk between adjacent channels. The end result is a movie
of the droplets dancing through the channels.

“Our approach allows us to make measurements over a comparatively large
area over the chip. Most microscopes have a relatively limited view and
cannot see how the whole system is working. With our device, we can
place lenses wherever we want to make a measurement,” adds Crozier.

The system can detect nearly 200,000 drops per second, or about four
times the existing state-of-the-art detection systems. Further, the lens
array is scalable, without any loss in efficiency, and can be peeled
on-and-off like a reusable sticker. Ultimately, the integrated design
offers the sensitivity of a larger confocal microscope and the ability
to measure over a larger area, all in a much smaller, cheaper package.

“Because we have this massively parallel approach—effectively like 62
microscopes—we can get very high measurement or data rates,” says
Crozier. “This device has shown we can measure up to 200,000 drops per
second, but I think we can push it even further.”

Nanophotonics experts Schonbrun and Crozier originally developed the
zone-plate technology to enhance optical tweezers so they could grab
particles in a liquid using light. Using the high numerical aperture
that makes efficient optical tweezers, they realized that arrays of zone
plates could also be used to implement an efficient and scalable optical
detection platform.

The researchers, who have filed a patent on their invention, are
optimistic that with further research and development, the device could
enhance a range of microfluidic and microfluidic-based lab-on-chip
devices and speed the advance of using them for applications such as
in-the-field biological assays.

Crozier and Schonbrun’s co-authors included postdoctoral fellows Adam R.
Abate and Paul E. Steinvurzel, both in SEAS, and David. A. Weitz,
Mallinckrodt Professor of Physics and of Applied Physics, in SEAS and
the Department of Physics.

The authors acknowledge funding from the Defense Advanced Research
Projects Agency. Fabrication work was carried out at the Center for
Nanoscale Systems at Harvard, which is supported by the National Science
Foundation.