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Microfluidics is triggering technological revolutions in many disciplines, including implantable drug delivery systems, to detection of biological or chemical hazards, to DNA analysis.

Microfluidics deals with the behaviour, precise control and manipulation of fluids that are geometrically constrained to a small, typically sub-millimeter, scale. Microfluidics is a multidisciplinary field and is used in the development of inkjet printheads, DNA chips, lab-on-a-chip technology, micro-propulsion, and micro-thermal technologies. Potential applications of this new field range from chemical lasers, to implantable drug delivery systems, to detection of biological or chemical hazards, to DNA analysis.

The basic idea behind microfluidics is to implement operations that used to require an entire lab in a single micro-sized device. A lab-on-a-chip is a device that integrates one or several laboratory functions on a tiny single chip to achieve automation and high-throughput screening. Lab-on-a-chips deal with the handling of extremely small fluid volumes down to less than pico-liters. Lab-on-a-chip devices are a subset of Micro-electro-mechanical systems (MEMS) devices and often indicated by “Micro Total Analysis Systems” (µTAS) as well.

At small scales (channel size of around 100 nanometers to 500 micrometers) some interesting and sometimes unintuitive properties appear. In particular, the Reynolds number (which compares the effect of the momentum of a fluid to the effect of viscosity) can become very low. A key consequence is co-flowing fluids do not necessarily mix in the traditional sense, as flow becomes laminar rather than turbulent; molecular transport between them must often be through diffusion

Developments in the field of microfluidics have triggered technological revolutions in many disciplines, including chemical synthesis, electronics, diagnostics, single-cell analysis, micro- and nanofabrication, and pharmaceutics.

Moreover, as with many other scientific fields, research for military purposes stimulated a lot of effort on the development of microfluidics technology as a tool of defense against potential bacteriological threats. In particular, government institutions, such as the DARPA (Defense Advanced Research Projects Agency), commissioned microfluidics systems for fast and in-situ detections.

Profusa wins $7.5m DARPA Grant for Implantable Biosensors

San Francisco-based tissue-integrated sensor maker Profusa said today it won a $7.5 million grant from the Defense Advanced Research Projects Agency and the U.S. Army Research Office for the development of implantable biosensors.

The new sensors will be designed for the simultaneous, continuous monitoring of multiple body chemistries, the company said, with their initial use slated to provide real-time monitoring of combat soldier’s health status.

“Profusa’s vision is to replace a point-in-time chemistry panel that measures multiple bio­markers, such as oxygen, glucose, lactate, urea, and ions with a biosensor that provides a continuous stream of wireless data. We are gratified to be awarded this grant to accelerate the development of our novel tissue-integrating sensors for application to soldier health and peak performance,” CEO Ben Hwang said in prepared remarks.

The biosensors are placed just under the skin with a specially designed injector, Profusa said. Each sensor is a flexible fiber, between 2 and 5 mm long, composed of “smart hydrogel,” and are designed to be integrated into the body’s tissue to overcome the foreign body response for more than 1 year, the company said.

“Long-lasting, implantable biosensors that provide continuous measurement of multiple body chemistries will enable monitoring of a soldier’s metabolic and dehydration status, ion panels, blood gases, and other key physiological biomarkers. Our ongoing program with Darpa builds on Profusa’s tissue-integrating sensor that overcomes the foreign body response and serves as a technology platform for the detection of multiple analytes,” CTO Natalie Wisniewski said in a prepared statement.

 

Microfluidic Laboratory-on-a-chip

One of the main microfluidic applications is the so-called Laboratory-on-a-chip, that has the aim to integrate all the functionalities of an entire laboratory within a single microfluidic chip. For instance, in cell biology, researchers are able to culture their cells within a microfluidic device with the possibility to inject drugs and see live the response of the sample at a cellular basis. In this regard, the possibility to have complete control over the surrounding environment has been deeply explored.

This approach can be a game changer in applications  ranging from cancer research to defense against chemical agents, and it holds the promise of providing orders of magnitude advantage in speed and cost.

 

Scientists develop ‘lab on a chip’ that costs 1 cent to make

Researchers at the Stanford University School of Medicine have developed a way to produce a cheap and reusable diagnostic “lab on a chip” with the help of an ordinary inkjet printer.

“Enabling early detection of diseases is one of the greatest opportunities we have for developing effective treatments,” Esfandyarpour said. “Maybe $1 in the U.S. doesn’t count that much, but somewhere in the developing world, it’s a lot of money.

A combination of microfluidics, electronics and inkjet printing technology, the lab-on-a-chip is a two-part system: A clear silicone microfluidic chamber for housing cells sits on top of a reusable electronic strip. A regular inkjet printer that can be used to print the electronic strip onto a flexible sheet of polyester using commercially available conductive nanoparticle ink.

Designed as a multifunctional platform, one of its applications is that it allows users to analyze different cell types without using fluorescent or magnetic labels that are typically required to track cells. Instead, the chip separates cells based on their intrinsic electrical properties: When an electric potential is applied across the inkjet-printed strip, cells loaded into the microfluidic chamber get pulled in different directions depending on their “polarizability” in a process called dielectrophoresis. This label-free method to analyze cells greatly improves precision and cuts lengthy labeling processes.

The tool is designed to handle small-volume samples for a variety of assays. The researchers showed the device can help capture single cells from a mix, isolate rare cells and count cells based on cell types.

The low cost of the chips could democratize diagnostics similar to how low-cost sequencing created a revolution in health care and personalized medicine, Davis said. Inexpensive sequencing technology allows clinicians to sequence tumor DNA to identify specific mutations and recommend personalized treatment plans. In the same way, the lab on a chip has the potential to diagnose cancer early by detecting tumor cells that circulate in the bloodstream. “The genome project has changed the way an awful lot of medicine is done, and we want to continue that with all sorts of other technology that are just really inexpensive and accessible,” Davis said.

The technology has the potential to not only advance health care, but also to accelerate basic and applied research. It would allow scientists and clinicians to potentially analyze more cells in shorter time periods, manipulate stem cells to achieve efficient gene transfer and develop cost-effective ways to diagnose diseases, Esfandyarpour said. The team hopes the chip will create a transformation in how people use instruments in the lab. “I’m pretty sure it will open a window for researchers because it makes life much easier for them — just print it and use it,” he said.

 

Microfluidic Cooling

The challenge in scaling chips and increasing clock rates is mainly due to limitations in removing excess heat. In order to overcome the stubborn heat removal problem, air and liquid based cooling with fans and metallic plates is used. However, these methods have low heat-removal efficiency and undesired thermal resistance.

To solve these problems, microfluidic cooling approaches are emerging, which exploit microchannels positioned on wafer surfaces. Microfluidics are promising for addressing hot spots in mobile devices, not only for high-performance computing applications. They can cool hot spots directly, and are useful for thinned die and 3D stacks.

 

DARPA’s Intrachip/Interchip Enhanced Cooling (ICECool)

The increased density of components in today’s electronics has pushed heat generation and power dissipation to unprecedented levels. Current thermal management solutions, usually involving remote cooling, where heat must be conducted away from components before rejection to the air, are unable to limit the temperature rise of today’s complex electronic components without adding considerable weight and volume to electronic systems. The result is complex military systems that continue to grow in size and weight due to the inefficiencies of existing thermal management hardware.

DARPA’s Intrachip/Interchip Enhanced Cooling (ICECool) program seeks to overcome the limitations of remote cooling. ICECool will explore ‘embedded’ thermal management by bringing microfluidic cooling inside the substrate, chip or package and by including thermal management in the earliest stages of electronics design. Success with ICEcool may help close the gap between chip-level heat generation density and system-level heat removal density in high-performance electronic systems, such as computers, RF electronics and solid-state lasers.

Microelectronics experts at IBM Corp. are taking the next step in a U.S. military research program to design convective or evaporative microfluidic cooling directly into microchip designs and packaging. For the latest contract, IBM electronics thermal management experts will build on completed research in military electronics to help designers make substantial reductions in size, weight, and power consumption (SWaP) of computer chips, while retaining or advancing chip performance.

The BAE Systems Electronic Systems segment in Merrimack, N.H., and the Boeing Co. Defense, Space & Security segment in El Segundo, Calif., also are involved in the DARPA ICECool program. BAE Systems and Boeing are working on the ICECool Applications program to find new approaches to electronics thermal-management in military embedded systems and RF MMICs.

IBM will continue searching for ways to shrink chip-cooling technologies such that they can build cooling into the chip itself. The goal is to close the gap between chip and chip-cooling technologies for military electronics like computers, RF transceivers, and solid-state lasers.

Cooling High-Powered Systems From Within

Qorvo and Lockheed Martin are working to apply its thermal management techniques with Qorvo’s gallium nitride (GaN) on silicon carbide (SiC) QGaN15. This technology has the exciting potential to cool systems that need it the most — from sophisticated military equipment such as radars and electronic warfare to high-performance computers and servers.

This approach can also be extended to existing or future die technology such as gallium arsenide (GaAs) and GaN on diamond. Roger Hall, general manager of Qorvo’s Infrastructure and Defense Products said, “Qorvo has been working with DARPA since 2013 on breakthroughs involving GaN on diamond. Now we’re thrilled to be working on a new microfluidic cooling approach for GaN and other microelectronics.”

Significant Increase in RF Output Power

Qorvo and Lockheed Martin demonstrated an impressive, six-times increase in RF output power with its new chip-level heat removal, versus conventional cooling techniques. Hall said, “Fast and cost-effective cooling for high-powered microchips has far-reaching applications for the hundreds of chips inside everyday devices. By increasing the thermal conductivity and reducing device temperature, we are paving the way for new generations of GaN devices that may be much smaller than today’s products.”

Qorvo and the ICECool team is developing a transmit antenna prototype and increasing the technology readiness level of this new cooling technique, so the electronics we all rely on perform effectively and efficiently.

 

Other applications of microfluidics  include the implementation of fluidic valves and channels with liquid metals, thus enabling reconfigurable radio-frequency antennas 

Tunable Liquid Metal Antennas

Researchers have held tremendous interest in liquid metal electronics for many years, but a significant and unfortunate drawback slowing the advance of such devices is that they tend to require external pumps that can’t be easily integrated into electronic systems.

Team of North Carolina State University (NCSU) researchers have created a reconfigurable liquid metal antenna controlled by voltage only by using electrochemical reactions to shorten and elongate a filament of liquid metal and change the antenna’s operating frequency. Applying a small positive voltage causes the metal to flow into a capillary, while applying a small negative voltage makes the metal withdraw from the capillary.

The shape and length of the conducting paths that form an antenna determine its critical properties such as operating frequency and radiation pattern. “Using a liquid metal—such as eutectic gallium and indium—that can change its shape allows us to modify antenna properties more dramatically than is possible with a fixed conductor,” explained Jacob Adams, coauthor and an assistant professor in the Department of Electrical and Computer Engineering at NCSU.

The positive voltage “electrochemically deposits an oxide on the surface of the metal that lowers the surface tension, while a negative potential removes the oxide to increase the surface tension,” Adams said. These differences in surface tension dictate which direction the metal will flow.

This advance makes it possible to “remove or regenerate enough of the ‘oxide skin’ with an applied voltage to make the liquid metal flow into or out of the capillary. We call this ‘electrochemically controlled capillarity,’ which is much like an electrochemical pump for the liquid metal,” Adams noted.

“Mobile device sizes are continuing to shrink and the burgeoning Internet of Things will likely create an enormous demand for small wireless systems,” Adams said. “And as the number of services that a device must be capable of supporting grows, so too will the number of frequency bands over which the antenna and RF front-end must operate.  Liquid metal systems “yield a larger range of tuning than conventional reconfigurable antennas, and the same approach can be applied to other components such as tunable filters,” Adams said.

In the long term, Adams and colleagues hope to gain greater control of the shape of the liquid metal — not only in one-dimensional capillaries but perhaps even two-dimensional surfaces to obtain nearly any desired antenna shape. “This would enable enormous flexibility in the electromagnetic properties of the antenna and allow a single adaptive antenna to perform many functions,” he added.

 

Other applications

 A related microfluidic fabrication technology that has been developed at Lincoln Laboratory is low-voltage electrowetting. In this process, a thin dielectric layer is applied to the walls of microfluidic channels, and the application of suitable voltages enables the switching and propagation of two-component fluids (such as oil drops in water) in complex paths.

Electrically controlled microfluidic circuits can be designed and implemented, including pumps, valves, mixing elements, and filters. Besides biomedical applications, the Chemical, Microsystem, and Nanoscale Technologies Group is pursuing applications of low-voltage electrowetting in microoptics and microhydraulics. In microoptics, the group has demonstrated the fabrication and functionality of switchable liquid lens arrays, with dimensions of individual lenses down to 50 µm and even less, capable of changing focus over a wide range as the applied voltage changes the shape of the oil-water interface.

A related application envisions electrowetting-based optical beam steering, where the variable-focus liquid microlenses are replaced with variable-angle liquid microprisms. The group’s initial studies into microhydraulics applications have recently shown efficient fluid displacement through arrays of microchannels in a conductive matrix, leading to the development of pistons and actuators.

 

 

References and Resources also include:

https://www.ll.mit.edu/mission/electronics/cmnt/microfluidics/microfluidics.html

http://med.stanford.edu/news/all-news/2017/02/scientists-develop-lab-on-a-chip-that-costs-1-cent-to-make.html

http://www.darpa.mil/program/intrachip-interchip-enhanced-cooling

http://www.qorvo.com/innovation/customer-stories/qorvo-and-lockheed-martin-microchip-cooling-for-darpa-icecool-program

http://www.cytofluidix.com/profusa-wins-7-5m-darpa-grant-for-implantable-biosensors/

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