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The microchip has five inlets and one outlet, all linked to tubing via the magnetic connectors. The inset at upper right shows the setup of the tube-magnet combination. Image: G. Cooksey, NIST

Designing microfluidic devices presents a variety of challenges, many of which are intrinsically tied to the small size of the products and their parts. Among the most frustrating design aspects of the miniature devices, according to researchers at the National Institute of Standards and Technology (NIST; Gaithersburg, MD), are the connectors that form the fluid pathways from external liquid pumps and regulators to the chip. Taking matters into their own hands, the NIST scientists have developed a new magnetic connector that they believe will improve microfluidic device design.

Typically, connectors for microfluidic applications require gluing the tubing directly to the chip or employing a male-female connection that joins the tubing to the male component. But these methods are associated with many potential flaws and defects, such as broken bonds or leaks, cracked chips from heat-curing the glue, or devices rendered unusable from rogue glue that runs into the channels. Using magnets as the basis for the connection, the NIST connectors avoid these potential risk factors, however.

The scientists’ connector for microfluidic applications consists of a ring magnet engineered with an O-ring gasket on its underside and a tube in the center. The tube is positioned directly on top of the inlet or outlet port of a channel in the chip. To secure the magnet and tubing in place, a disc magnet goes on the bottom of the chip. In addition to being cost-effective, the connector is flexible, reliable, and enables quick assembly of the connection. Furthermore, it is reusable, unlike existing microfluidic connectors, the researchers claim. The magnetic connector appears to be suitable for use with most microfluidic devices, with the exception of iron-containing fluids, superparamagnetic particles, cells with magnetic particles, and temperatures greater than 80°C.

Click here to view a video demonstrating assembly and use of the connectors with a microfluidic chip.

Human red blood cells, in which membrane proteins are targeted and labeled with quantum dots, reveal the clustering behavior of the proteins. The number of purple features, which indicate the nuclei of malaria parasites, increases as malaria development progresses. The NIST logo at bottom was made using a photo lithography technique on a thin film of quantum dots, taking advantage of the property that clustered dots exhibit increased photoluminescence. (Credit: H. Kang/NIST and F. Tokumasu/NIAID.)

New research from the National Institute of Standards and Technology (NIST; Gaithersburg, MD) and the National Institute of Allergy and Infectious Diseases (NIAID; Bethesda, MD) enables scientists to observe and analyze activities that occur over hours or even days inside cells, opening the door to solving many mysteries associated with molecular-scale events.

The joint NIST/NIAID research team has discovered a method of using quantum dots to illuminate the cellular interior to reveal these slow processes. A type of nanoparticle, quantum dots are semiconductor particles that can be coated with organic materials tailored to be attracted to specific proteins within the part of a cell a scientist wishes to examine. When exposed to light, the dots glow.

“Quantum dots last longer than many organic dyes and fluorescent proteins that we previously used to illuminate the interiors of cells,” explains biophysicist Jeeseong Hwang, the NIST team leader. “They also have the advantage of monitoring changes in cellular processes while most high-resolution techniques like electron microscopy only provide images of cellular processes frozen at one moment. Using quantum dots, we can now elucidate cellular processes involving the dynamic motions of proteins.”

The NIST/NIAID study focused primarily on characterizing quantum dot properties, contrasting them with other imaging techniques. In one experiment, the team employed quantum dots designed to target a specific type of human red blood cell protein that forms part of a network structure in the cell’s inner membrane. When these proteins cluster together in a healthy cell, the network provides mechanical flexibility to the cell so that it can squeeze through narrow capillaries and other tight spaces. But when the cell gets infected with the malaria parasite, the structure of the network protein changes.

“Because the clustering mechanism is not well understood, we decided to examine it with the dots,” says NIAID biophysist Fuyuki Tokumasu. “We thought if we could develop a technique to visualize the clustering, we could learn something about the progress of a malaria infection, which has several distinct developmental stages.”

The team’s efforts revealed that as the membrane proteins bunch up, the quantum dots attached to them are induced to cluster and glow more brightly, permitting scientists to watch as the clustering progresses. More broadly, the team found that when quantum dots attach themselves to other nanomaterials, the dots’ optical properties change in unique ways in each case. They also found evidence that quantum dot optical properties are altered as the nanoscale environment changes, offering a greater possibility of using quantum dots to sense the local biochemical environment inside cells.

“Some concerns remain over toxicity and other properties,” Hwang says, “but altogether, our findings indicate that quantum dots could be a valuable tool to investigate dynamic cellular processes.”

For detailed information on this research, see Probing Dynamic Fluorescence Properties of Single and Clustered Quantum Dots Toward Quantitative Biomedical Imaging of Cells.

A prototype betavoltaic battery contains layers of silicon carbide and metal foil embedded with the radioactive isotope tritium. When high-energy electrons emitted by the decay of tritium hit the silicon carbide, it produces an electrical current that exits the cell through the metal pins. (Photo by Widetronix.)

Imagine not having to change your batteries for 25 years. Widetronix (Ithaca, NY) is developing a new type of betavoltaic battery that could eventually make that a reality.

Betavoltaic batteries harvest energy from the nuclear decay of isotopes, enabling them to produce very low levels of current and to last for decades. Their cells use a semiconductor to capture the energy in electrons, or beta particles, produced during the isotopic decay. The lifetime of betavoltaic devices depends on the half-lives of the radioisotopes that power them, which range from a few to 100 years.

Widetronix’s batteries are powered by the decay of the hydrogen isotope tritium into high-energy electrons. Since tritium has a half-life of 12.3 years, Widetronix puts twice as much tritium in its batteries as initially required to make batteries that will last for 25 years.

The batteries are composed of a metal foil impregnated with tritium isotopes and a thin chip of the semiconductor material silicon carbide, which can convert 30% of the beta particles that hit it into an electrical current. “Silicon carbide is very robust, and when we thin it down, it becomes flexible,” says Widetronix CEO Jonathan Greene. “When we stack up chips and foils into a package a centimeter squared and two-tenths of a centimeter high, we have a 1-µW product.” A prototype being tested by Lockheed Martin for military purposes produces 25 nW of power.

While Widetronix’s current invention is initially slated for military applications, the company is also working with medical device makers to develop models for implantable medical devices. Because these betavoltaic devices can withstand harsher conditions than chemical batteries and because of their long life spans, they are considered an attractive power source for medical implants.

For more information on this technology, see “A 25-Year Battery” in Technology Review, published by the Massachusetts Institute of Technology (Cambridge, MA).

Scientists are constantly looking to nature to guide them in the development of effective new technologies. Most recently, researchers hailing from several British and Australian universities have partnered to explore the unique surface properties of insect wings. Ultimately, the team’s goal is to replicate these desirable properties to produce novel polymeric coatings suitable for NEMS and MEMS systems, as well as for lab-on-a-chip devices for diagnostic applications.

Of particular interest to the researchers are wings that are superhydrophobic and those that are extremely lubricious. Some insect wings, according to the team, are so hydrophobic that they immediately repel even the smallest drop of water. Others exhibit negligible friction, which allows for minuscule dust particles to be sloughed away with little force, thereby exhibiting a self-cleaning capability of sorts.

Using atomic force microscopy, the researchers have determined that the forces required to slough nanoscopic dust particles off of a wing fall in the range of 2 to 20 nN. Upon obtaining these data, the researchers then employed an insect wing membrane to cast a polymer surface in polydimethylsiloxane (PMDS). In turn, they were able to replicate the structure of the wing.

Details of the project will be shared in an upcoming 2010 issue of the International Journal of Nanomanufacturing.

A mechanical microdrilling technique developed by Hitachi Via Mechanics enables the formation of 10,000 100-µm-diam throughholes on a 0.5-mm-thick wafer.

Microdrilling techniques developed by Hitachi Via Mechanics (San Jose) may offer a cost-effective alternative to laser-based catheter drilling. Enabling the high-volume production of throughholes measuring 100 µm in diameter and smaller, the technology can be employed in conjunction with PVC, Ultem, and other compounds used in the medical device industry.

Hitachi engineers in the United States and Japan collaborated on the development of the technology, which has been applied to the ND-1S single-spindle modular system with vision and the ND-Q six-spindle production-level microhole mechanical drilling system. This six-spindle machine is compatible with a range of fixtures to suit different part configurations.

For use with a variety of polymer sheet, tube, and composite materials, the technology can form 10,000 100-µm-diam throughholes on a 0.5-mm-thick cast polyimide wafer. This capability indicates that many existing laser processes used to drill high-density hole arrays could be replaced by a simpler mechanical method at about one-fifth the cost, according to the manufacturer. Mechanical drilling processes are especially effective in applications that suffer from surface or material thickness variations, since a mechanical tool, rather than the focal position of a lens, defines the hole size.

There have been a lot of exciting developments recently in the field of biodegradable electronics. As we reported yesterday, a research project yielded flexible silicon electronics on silk substrates that almost completely dissolve inside the body. Now, a group from Stanford University has laid claim to being the first to develop fully biodegradable semiconducting materials.

Led by Zhenan Bao, associate professor, department of chemical engineering at Stanford, the team has managed to build biocompatible organic electronics that can dissolve in the body for potential use in tissue engineering or drug-delivery applications. The electronics are constructed from a biodegradable semiconducting material that, according to MIT Tech Review, “resembles skin-pigment melanin and gold and silver electrical contacts.”

Discovering that the electronics were stable in water, the team simulated the conditions of the body using a slightly basic salt-based solution. These conditions spurred the degradation of the electronics, which ultimately dissolved in the body. Only metal electrical contacts measuring less than 1 nm thick were present after 70 days. The researchers acknowledge, however, that in order to fulfill a function prior to degradation, the electronics would likely have to be encapsulated and then exposed to the body’s natural conditions once they have completed the assigned task.

A clear silk degradable film about 1 cm square with six silicon transistors on its surface can be implanted in mice. The orange liquid on the hair is a disinfectant used during surgery. (Photo by John Rogers and Fiorenzo Omenetto.)

A group of scientists from several universities are developing thin, flexible silicon electronics on silk substrates that almost completely dissolve inside the body. The new technology offers a range of advantages. While electronics must usually be encased to protect them from the body, these electronics do not require protection. In addition, the silk substrate conforms to biological tissue before melting away over time, and the thin silicon circuits left behind do not cause irritation because they are only a few nanometers thick.

“Current medical devices are very limited by the fact that the active electronics have to be ‘canned,’ or isolated from the body, and are on rigid silicon,” says Brian Litt, associate professor of neurology and bioengineering at the University of Pennsylvania (Philadelphia). Litt, who is working with the silk-silicon group to develop medical applications for the new devices, comments that they could interact with tissues in new ways. While the group has built arrays of transistors on thin silk films, it is developing silk-silicon LEDs that could act as photonic tattoos for showing blood-sugar readings and designing arrays of conformable electrodes that could interface with the nervous system.

To make the devices, silicon transistors about 1 mm long and 250 nm thick are collected on a stamp and then transferred to the surface of a thin film of silk. The silk holds each device in place, even after the array is implanted in an animal and wetted with saline, causing it to conform to the tissue surface.

Last year, John Rogers, professor of materials science and engineering at the Beckman Institute at the University of Illinois (Urbana-Champaign), developed flexible, stretchable silicon circuits whose performance matches that of their rigid counterparts (see “Foldable, Stretchable Circuits,” Technology Review, March 28, 2008). To make these devices biocompatible, Rogers’s lab collaborated with bioengineering professors Fiorenzo Omenetto and David Kaplan from Tufts University (Medford, MA), who made nanopatterned optical devices from silkworm-cocoon proteins (see “Spinning Silk into Sensors,” Technology Review (January/February 2009).

Last year, a cross-disciplinary team of researchers reverse-engineered the communications protocol of an implantable cardioverter-defibrillator (ICD). In doing so, the team succeeded in extracting secure patient data, depleting battery power, changing the device’s settings, and inducing fibrillation. And it got the industry buzzing. Apparently, it also caught the attention of fellow researchers: European researchers have responded to this wireless worry with an approach to safeguarding implants against heart device hackers.

Although the probability of implant hacking seems to be low, researchers from the Swiss Federal Institute of Technology in Zurich and the French National Institute for Research in Computer Science and Control have joined forces to protect devices in the event of a wireless attack. According to an article in the MIT Technology Review, French researcher Claude Castelluccia and his colleagues examined the prospect of enhancing device security by creating a direct correlation between implant access and proximity of the communicating device.

The concept of requiring wireless reading devices to be physically near an implant in order to communicate with it or access it is not a new one, according to Castelluccia. However, he notes that this security measure can be circumvented by using a strong radio transmitter to give the illusion of proximity to the device. With this issue in mind, the researchers have developed a method that relies on ultrasound waves and radio signals in order to obtain an accurate assessment of proximity. Their scheme permits implant access up to 10 m away from the device; but, it requires a series of authentication steps in order to gain access. The exception for the protocol, however, would be during an emergency, in which case anyone as close as 3 cm can gain automatic access for safety and patient-care purposes.

With a prototype under its belt, the research team has patented the technology and is speaking with potential partners about developing a prototype.

This story has caught MPMN’s attention. What do you think: Is the possibility of such a threat that real? Would you consider integrating such a security measure into your implant? Let us know!

Read more about the original research in an MPMN editor’s column published last year.

Among the most prominent news stories of the past year is that of the decline of the domestic automotive industry and, with it, the plight of Michigan manufacturers. To weather the economic storm, suppliers to the automotive industry have had to seek business in other sectors. And, supported in many ways by Michigan-based organizations, many suppliers have set their sights on the relatively stable medical device industry.

Crain’s Detroit Business featured coverage of the 5th-annual MichBio Expo last week, specifically highlighting a panel discussion focusing on diversifying to serve the medical device industry. In it, Jeff Kaczperski, president of injection molder Omega Plastics (Clinton Township, MI), offered a variety of tips for suppliers looking to diversify into the lucrative medtech marketplace. According to the article, his advice included familiarizing oneself with the market, devising a concrete business strategy and specific steps for fostering growth, and preparing to respond to customers’ potential questions of loyalty should the auto industry bounce back in full force.

But is the transition really that simple? And, more importantly, what does this mean for medical device OEMs?

MPMN touched on these issues in an editorial earlier this year.  As we noted, these newcomers could present cost benefits to medical device OEMs. However, the real issue with the diversification effort is: Will quality be compromised? Can automotive suppliers cater to the stringent requirements and demands of the medical device industry with such proposed ease?

What do you think, faithful blog followers? Is diversification a good thing for the medical device industry, or are you troubled by the potential consequences?

A low-power neural amplifier collects electrical signals from nerves and minimizes electrical noise. (Photo: Brian Otis, University of Washington.)

Electrical engineers at the University of Washington (Seattle) have developed an implantable neural sensing chip that requires low power. Known as NeuralWISP, the new sensor platform draws power from a radio source situated up to a meter away. In contrast, some wireless medical devices such as cochlea and retinal implants rely on inductive coupling, requiring the power source to be centimeters away from the device.

The device contains a microprocessor powered by a commercial radio-frequency reader that doubles as a data-collection device—the same equipment used to power and read information from radio-frequency identification (RFID) tags. The new technology could eventually find its way into sophisticated implantable medical devices.

While neural implants have shrunk in size, most implantable devices still require multiple components that are larger than the transistors on the microcontroller, such as a clock for timing operations and an antenna for communication and power harvesting, remarks Brian Otis, professor of electrical engineering at the University of Washington and lead researcher on the NeuralWISP project.

Placed on a circuit board slightly more than 2 cm long, the NeuralWISP is a collection of small low-power components such as a specialized signal amplifier. A future version will integrate all components onto a single 2-mm-long chip. The circuitry converts usable power from the roughly 430-µW reader to a voltage that can turn on the microcontroller. This microcontroller, in turn, controls the sensor and its timer and runs instructions that allow data to be sent back to the reader.

One of the main ways to save power, says Otis, was to reduce how often the sensor measured electrical signals produced by neurons. The researchers programmed the microcontroller to wake up when an electrical spike occurred and record only the signals that were above a certain threshold.

In addition to some circuit design considerations, researchers built a small signal amplifier that boosts the electrical signal from neurons while minimizing electrical noise. For this, they split the incoming signal into two parts. The amount of incoming electricity from neural activity is the same, but by splitting it between a pair of transistors within the circuit, the amount of noise is cut in half.

A tethered moth is connected to the neural sensing system, which records activity from its central nervous system as it flaps its wings. (Photo: Brian Otis, University of Washington.)

To sense central nervous system activity, the researchers devised experiments involving a moth, collecting data on electrical signals from the moth’s wing muscles. The tests showed the frequency with which the moth flapped its wings. While the current system is too large to allow the moth to fly freely, an upcoming chip is small enough to enable unencumbered flight, Otis says.

“Most implantable devices have used lower frequencies,” says Josh Smith, principal engineer at Intel and organizer of the WISP Summit, a workshop on wirelessly powered sensor networks and computational RFID held November 3 in Berkeley, CA. Lower frequency also means that the devices must be read at close range. Using commercial RFID readers allows the device to be powered and data to be read from further away, Smith adds.

However, it is still an open question whether the antenna will maintain the long range once it is implanted in animal tissue because the signal might be absorbed. “Measuring moths is a good fit for this approach, since the antenna does not have to go inside the animal’s tissue,” Smith comments.

Additional information on this technology is available in Technology Review, published by the Massachusetts Institute of Technology (Cambridge, MA).