Spotlight on Pumps and Valves

Solenoid pinch valves
The Intelivalve line of solenoid pinch valves from Acro Associates Inc. is designed to accommodate the types of tubing used most frequently in fluid-based medical devices with single-use or disposable fluid paths. Thus, it can accommodate 1/8- to 7/16-in. OD flexible tubing, tubing with durometers up to 75 Shore A, and tubing materials with media pressure ratings up to 30 psi. The valves have a dedicated sensor and controller; thus, not only are power management and state sensing built-in features, but the valves emit almost imperceptible noise and offer an option for tube detection, cycle monitoring, and fault logging. To facilitate integration, multiple controllers can be linked and enabled to communicate via a controller area network or the RS-422 or RS-485 interface. These pinch valves are suited for use in dialysis treatment equipment, blood-collection devices, perfusion systems, and drug-administration systems. They can also serve as emergency shutoff valves, direct administration devices, or valves for precise dosing, filling, or mixing.
Acro Associates Inc.
Concord, CA

Microfluidic valves
Combining the proven rocker principle with an innovative actuator enables Twin Power microfluidic valves from Burkert Fluid Control Systems to maintain given levels of performance and reliability in a smaller valve design with lower power consumption. The dual-solenoid valves are available in 10-, 16-, and 22-mm sizes. They also exhibit the flow and pressure resistance typically found in larger valves, making them suitable for applications in which space is critical or strong performance is needed. The 10-mm valve comes with orifices sized up to 1.6 mm and with pressure resistance as high as 73 psi; the 16-
and 22-mm models are available with a 3.0-mm orifice. Maximum pressure resistance is 29 psi for the 16-mm valve and 73 psi for the 22-mm valve.
Burkert Fluid Control Systems
Irvine, CA

Microminiature vacuum pumps
High-performance, maintenance-free Type NPK04 microminiature swing-piston pumps for transferring, evacuating, or compressing air in medical and analytical instrumentation generate high flows at vacuum or pressure. Available from KNF Neuberger Inc., the 2.5-in.-long pumps deliver free-flow rates to 4 L/min and can be optimized to produce elevated levels of vacuum or pressure: up to 21 in.Hg or 45 psig, respectively. Also, standard pumps can be customized to meet particular OEM requirements. The swing piston incorporated in the design enables the pump to move media oil-free. Users can specify standard dc motors or brushless dc motors. Supplied ready to install and able to operate in any position, these pumps run quietly with minimal vibration and provide sustained energy-efficient service.
KNF Neuberger Inc.
Trenton, NJ

Solenoid pump
Designed to offer medical device engineers design flexibility, the LPL2 inert solenoid pump from The Lee Co. has a distinctively engineered port head that accommodates tubing connections and manifold mounting. This design enables the medical device developer to test the fluidic system using connections to soft 1/16-in. tubing. Once the system design has been finalized, the same pump can then be manifold-mounted by means of standard O-rings. The pump additionally features a contoured end cap that is compatible with standard AMP connectors, providing secondary connector retention.
The Lee Co.
Westbrook, CT

Piezoelectric diaphragm micropumps
Based on piezoelectric diaphragm pump technology, the self-priming micropumps in the MP-6 series from Servoflo Corp. deliver air, gases, or liquids in low-flow portable medical equipment applications, such as drug-delivery devices, infusion pumps, nebulizers, respiratory equipment, and point-of-care platforms. These stock pumps measure 30 × 15 × 3.8 mm, consume less than 200 mW of power, and are capable of cycling several-hundred times per second. Typical flow values are 18 ml/min maximum with 100-mbar backpressure for gas and 7 ml/min with 600-mbar backpressure for water. Custom pump modifications can be made to meet customer requirements. A polypropylene version is available for handling corrosive media. Evaluation kits are available.
Servoflo Corp.
Lexington, MA

Brushless dc air pump
The 230-series brushless dc WOB-L air compressor is designed for medical device applications calling for a lightweight, compact pump with variable output. The 3.8 × 2.64 × 3.63-in., 1.2-lb pump from Thomas Div. generates output between 1000 and 3000 rpm and features an efficient brushless dc motor, an enclosed crankcase to keep noise to 40 dBa, and proprietary piston technology. Maximum flow is 0.50 cu ft/min, and maximum pressure is 30 psig. The pump runs on 12 V, draws 3.3 A of current, and has a motor rating of 40 W. It operates at temperatures between 50° and 104°F.
Thomas Div.
Sheboygan, WI

OEM pumps for surgical ablation
The 400RXMD range of OEM pumps, based on the manufacturer's RX pump technology, is designed for such surgical ablation applications as treatment of cardiac arrhythmia and cancer. Watson-Marlow Pumps Group has incorporated numerous customer-requested improvements into this pump series. Among them are a choice of pressure settings to accommodate specific application requirements, a mechanism that enhances flow accuracy, and a tube holder designed to ensure that a newly loaded tube goes into the right position whenever the safety lid is closed. Pressure, flow, and rotational direction can be set to suit the user's needs. Used in equipment employing radio-frequency ablation, the pump circulates cooling fluid to provide precise temperature control so that the treatment will be more effective and prevent scarring. It is available in 10 variants offering flow rates to 500 ml/min at 550 rpm and pressure settings ranging up to 8 bar.
Watson-Marlow Pumps Group
Wilmington, MA

Marshall Manufacturing Offers Precision Wire and Tube Bending (MD&M West Exhibitor)

A medical manufacturing partner that prioritizes prototyping and the use of custom tooling for material machining and forming offers services in automated and robotic precision wire and tube bending. Tubes 0.050 to 0.500 in. in diameter and wire in diameters of 0.050 to 0.375 in. can be formed. The customer-focused ISO 13485–certified company assists clients with decisions about materials and processes that will lead to the achievement of the best form, function, and manufacturability for any medical part. Using such techniques as electrical-discharge machining, flaring, swaging, and laser machining, the company manufactures parts from premachined wire and tubing. Premachining operations include precision cutoff, turning, and milling of special tips, such as trocar, bullet, barbed, pencil, and other types, as well as cross holes, grooves, and slots, all with precise tolerances. Premachined parts can be bent to orient their machined features on each end to a precise final destination via customized separators and indexing.

Minneapolis

Marshall Manufacturing will be exhibiting at MD&M West in Booth #1191

Valtronic Expands Electronic Manufacturing Capability (MD&M West Exhibitor)

Solon, OH
 

Valtronic will be exhibiting at MD&M West in Booth #1586


Teknor Apex Adds Two High-Hardness Grades to TPV Elastomers

 A supplier has added two high-hardness grades to its series of thermoplastic vulcanizate (TPV) elastomers. Medalist MD-200 now includes compound MD-240 at 87 Shore A and MD-245 at 43 Shore D, the latter grade having a durometer roughly equivalent to 93 Shore A. The line of resilient, high-purity, nonhygroscopic compounds designed and qualified to substitute for rubber in medical device applications now includes grades ranging in Shore A durometer from an ultrasoft 15 through the hard compounds just introduced. Their rubber-like properties include low long-term compression set, high fatigue resistance, prolonged flex life, stability at high temperatures, abrasion resistance, and long-term sealability. Able to be extruded, injection-molded, and blow-molded, the hard grades are suited for the production of peristaltic tubes, collection and drainage tubes, vial, cap, and plug stoppers, seals and gaskets, device handles, ergonomic soft grips, valves, and diaphragms.

Pawtucket, RI

Teknor Apex will be exhibiting at MD&M West in Booth #2526


Daniel Kraft on How Exponential Technologies Will Reboot Healthcare

Daniel Kraft, MD, executive director of FutureMed.

"Medicine is certainly ripe for some sort of disruption," says Daniel Kraft, MD, the Stanford and Harvard-trained executive director of FutureMed at Singularity University in Silicon Valley. The fuel for that disruption is a variety of technologies with rapid growth curves and the innovators who help leverage them to change the status quo. Artificial intelligence, 3D printing, genomics, Big Data, mobile technology, regenerative medicine, and smart user interfaces each could have a significant long-term impact on the biomedical and life science industries. As diverse fields converge and become accessible at ever-lower price points, they could have a tremendous impact on healthcare, Kraft says.

Developers of medical devices or other healthcare-related products and services can tap into the power of such technologies to help reinvent and re-imagine how healthcare is practiced, Kraft says. He will deliver a keynote on the subject titled "The Future of Health and Medicine; Where Can Technology Take Us?" at MD&M West in Anaheim, CA on February 13. "Hopefully we'll look back in ten years and some of the things we are doing now in healthcare will look antiquated as how we used to go banking or rent videos a decade ago."

Of Hammers, Nails, and Exponentials

According to the popular expression, "if all you have is a hammer, everything looks like a nail." Healthcare needs to expand those proverbial hammers and nails, says Kraft, who has a fondness for reflecting on the tools that have the greatest potential to improve medicine.

Kraft's keynote at MD&M West will also provide a recap of the technological advances discussed at his FutureMed conference. Held February 4-9, that event will bring together more than 50 faculty who will discuss everything from brain-computer interfaces to 3D printing. Kraft's talk also will touch on his own experience as the inventor of the Marrow Miner, a minimally invasive bone-marrow harvesting device that is still under development. More recently, he founded the startup Intellimedicine, which aims to help make medicine more personalized and evidence-based.

The Future of Health and Medicine: Where Can Technology Take Us?

Daniel Kraft, MD regularly speaks on the future of health and medicine. His keynote at MD&M West will examine themes similar to those featured in the TED talk above, including artificial intelligence and nanotechnology.

Other developments to be discussed in Kraft's talk include the burgeoning field of mHealth. "You can now go to an Apple store or a Best Buy and on the shelf they have a whole section of health-related connected devices. What are the implications of that--both for developing new technologies, clinical trial, safety and efficacy, and beyond?" he asks. In addition, there are also recently FDA-approved smartphone-enabled medical devices such as the AliveCor iPhone ECG and the iPhone-compatible iBGStar glucose meter.

Another area to watch closely is genomics, along with the bigger "-omics" world. "A 23andMe genome analysis is now at $99. I had my exome sequenced at $999," Kraft says. "We are essentially at the $1000 genome today and it will be $100 genome in a couple years. How will that affect drugs or devices or the combination of the two?" he asks.

"Most people are quasi familiar with artificial intelligence through things like Siri. How will that affect everything from how drug and device reps interact with clinicians all the way to new ways of being able to access better care--on the workup and diagnosis side, picking the right therapy matched to the specific patient and their data and attributes?"

Also consider the popularity of wearable fitness devices. A recent example of such a product is the Basis watch, which measures one's heart rate and activity level. "It is a consumer device today. But imagine an FDA-approved version for, say, heart failure patients that can pick up heart rate and determine if they are taking too much beta-blocker," Kraft says. "It might also pick up volume status, blood pressure, and can utilized to modulate disease, and talk to their implanted defibrillator."

Another field to keep a close eye on is 3D printing. Kraft predicts that as the technology takes off, there will be an uptick in custom medical devices--for instance, prosthetic limbs that are personalized for a specific patient. He also points to the case of Tal Golesworthy, a British engineer with Marfan's syndrome who saved his own life by using 3D printing technology to develop a custom aortic graft.

3D printing, or, more broadly, digital manufacturing, could also dramatically shift the way medicine in practiced in a variety of settings. "You can print out point of care lab tests on paper, in some cases, that enable you to do diagnostics," Kraft says. Or you could use 3D printing technology to, say, make individualized orthopedic devices or custom instruments for surgery in remote locations. "It is already starting to play a role in some areas in healthcare and has the potential to change both the way we develop and test medical devices all the way to truly building bespoke components for individuals for a variety of healthcare needs."

FutureMed: Glimpsing into the Future of Healthcare

A paralyzed woman controls a robotic arm using thought alone. Leigh Hochberg, MD, PhD, who is featured in the clip above, will speak at this year's FutureMed event.  

Many of the topics highlighted above will be featured at a FutureMed on February 4-9. The theme of convergence is also built into the conference's design. "The main thing that makes FutureMed unique is that it brings folks from many different spectrums together as opposed to the traditional conference or meeting where it is often around a specific medical specialty or devices or pharma." "We are for example going to have a session on artificial intelligence in healthcare with Marty Kohn, MD, from IBM Watson as well as famed venture capitalist Vinod Khosla, musing on how we can disrupt healthcare using smart algorithms and this emerging generation of connected devices." On February 5, the event will be live-streamed at FutureMed2020.com/live.

While FutureMed is limited to less than 100 attendees, a public FutureMed event will be held on February 9 at the Computer History Museum in Mountain View, CA with the core FutureMed participants and faculty and is open to people working across the healthcare ecosystem. Topics to be covered in interactive workshops at the event include oncology, pain management, robotics, and artificial intelligence.

"We'll also have startups doing pitches to some seasoned and interesting investors from Esther Dyson to others," Kraft says. Also on display will be the Ekso Bionics exoskeleton device, which enables a paraplegic to walk, and an opportunity to try out the da Vinci surgical robot. Speakers at the Saturday event include brain-computer interface pioneer Leigh Hochberg, MD, PhD. "We are also going to have a session on artificial intelligence in healthcare by Marty Kohn, MD, from IBM Watson as well as famed venture capitalist Vinod Khosla, musing on how we can disrupt healthcare using smart algorithms and this new generation of connected devices." 

Brian Buntz is the editor-in-chief of MPMN. Follow him on Twitter at @brian_buntz.

Arab Health 2013 Preview

Arab Health 2013 starts today in Dubai. The event’s sponsors are promoting it as the world’s longest-running healthcare exposition and congress. This event, focused on the Middle East market, is now in its 38th year. This year, organizers expect 3,500 exhibitors and 83,000 attendees. Thirty-two country pavilions are planned, including a U.S. pavillion with companies and organizations from across the United States.

All totaled, there are 247 U.S. companies scheduled to exhibit throughout the 423,000 sq ft of show floor space. Many of the 3,500 exhibitors are easily recognizable in the American market, but others are not. The Middle East market appears to be growing and is propelled by abundant disposable income. And many other markets are looking to capitalize on this trend. In fact, nearly 40% of the exhibitors are from just four countries: the United States, Germany, UK, and China.

Arriving in Dubai, I was struck by contrasts. This city is home to incredible wealth and is progressive in its real estate and economic development. It has the world’s tallest building, the 160-story Burj Khalifa Tower,  and a man-made island in the shape of a palm tree. Yet, culturally it remains conservative in some respects. Arriving at the airport visitors are greeted by signs in the taxi/shuttle waiting area indicating one waiting area for men and another for women.

Don Beery is president of Blendon Group Consulting and executive director of the West Michigan Medical Device Consortium. Check back throughout the week for more of his posts from Arab Health 2013. 

Related Content

Arab Health 2013 Day One: Healthcare Opportunities Abound in the Middle East 

How Safe Are Lithium Ion Batteries for Medical Applications?

It is well known that lithium ion batteries can explode under certain conditions. For a visual demonstration, check out the video below (the pyrotechnics begin around 1:50 in). Lithium ion batteries also happen to be found nearly everywhere people are: in consumer electronics, in medical devices, as well as in vehicles such as hybrid cars and, more famously, the Boeing 787 Dreamliner.

It is still unclear what exact role lithium ion batteries played in recent fires in 787 Dreamliners, the batteries are generally safe under normal conditions, as a UL report titled "Safety Issues for Lithium-Ion Batteries" (PDF link) explains. As the title might indicate, however, have substantially higher energy density than other battery chemistries, which ups the risk for fire or explosions. In particular, they are susceptible to problems when they are overcharged or discharged quickly.

How safe are lithium batteries for medical devices? It depends on the device and the species of lithium battery technology in question. There are roughly half a dozen lithium-ion technologies available as well as lithium-polymer batteries, which has a different type of electrolyte.

On Quora, Razvan Baba, who has designed battery chargers, weighs in on the question above, pointing out that the safety window for lithium batteries is narrow. If the temperature is overly high or low, "something bad is bound to happen," he explains, pointing to the diagram on the right.

Also on Quora, Adam E. Piotrowski of CreateBigIdeas LLC acknowledges that the "the use environment of [consumer devices like portable electronics as well as hybrid cars] is very different from the demanding conditions of a commercial airliner." He adds: "Given the size of airplanes, the power demands for an airliner are likely different than those for an ICD or surgical tool, and meeting those demands under operating conditions may create different engineering challenges as compared to powering smaller, less-consuming devices and technologies."

The performance parameters of lithium ion batteries used in medical devices and consumer devices is better understood than it is in airliners, which undergo multiple takeoff and landing cycles daily.

"Answering the question whether or not lithium-ion batteries are safe for medical device applications comes down to understanding the environment and intended application of the device, and then making product and engineering decisions based on those needs and requirements," Piotrowski concludes.

Brian Buntz is the editor-in-chief of MPMN. Follow him on Twitter at @brian_buntz.

Helping Medical Devices Pass Their Tests

Cutting-edge combination products and novel orthopedic implants are improving treatment and enhancing patient care. But their complex nature has resulted in increased FDA scrutiny and a demand for more information to ensure the safety and efficacy of devices hitting the market. As a result, more-thorough medical device testing has become paramount. In turn, accommodating FDA's requests, optimizing devices, evaluating materials, and getting products to market quickly and on budget is putting medical device manufacturers to the test.

Scrutinizing Combination Products

Transdermal patches, specialty orthopedic implants, and drug-eluting stents are just a few of the medical devices that are fueling a rapidly growing market for combination products. As the industry anticipates a healthy future with combination devices, however, medical device manufacturers face a number of emerging challenges in regard to testing and regulatory affairs when bringing these hybrid products to market.

"A lot of the requests we're getting are from companies taking medical devices and fusing them with pharmaceuticals," remarks Eric Hill, business marketing and sales manager at Impact Analytical (Midland, MI). Impact's customers include manufacturers of drug-delivery patches, heart stents, and catheters, among others.

Testing such devices often focuses on whether the combination product contains the intended level of active pharmaceutical ingredients (API). It is also imperative to identify unwanted impurities and extractables, such as residual monomers in polymeric substances. "We always hear about bisphenol A (BPA) in consumer products," Hill adds, "but there's also BPA in medical devices."

EAG Life Sciences provides analytical support for extractables and leachables projects.

While there are definite cost, efficiency, and enhancement-of-care benefits to infusing medical devices with drugs, the medical device industry expects that such complex products will undergo more-rigorous regulatory scrutiny over time than noncombination devices, Hill notes. Thus, Allen Kesselring, director of scientific affairs at EAG Life Sciences (Maryland Heights, MO) observes that although formal regulatory requirements have not changed significantly, EAG is seeing an increase in FDA requests for additional information about combination products. "One thing that has definitely changed in the last couple of years is that the agency is reviewing these devices in a more thorough and detailed manner than before," he says.

In the last few years, FDA has increased its scrutiny of submitted information during the 510(k) review process in particular, says Jim Fentress, product development engineer at Gilero Biomedical (Research Triangle Park, NC). "This trend," he adds, "means that when a company files for 510(k) approval, there are more questions and a higher information threshold on what they expect to see from us."

That information threshold is particularly high for combination products because such products require regulatory filings for both the device and the API, Fentress comments. "A good example is an asthma inhaler. The device has to atomize the drug to the right particle size distribution so that a suitable therapeutic dosage reaches the right lung tissue. But the drug safety and pharmacokinetics must be well understood, independent of the device."

To carry out this more-stringent approach, FDA often collaborates with its colleagues from the Center for Drug Evaluation and Research (CDER). "Traditionally, CDER is the agency that evaluates pharmaceutical products, and as such, it looks at details associated with extractable leachables," Kesselring explains. "In the past, it never really touched medical devices."

EAG's testing experience with extractable leachables in pharmaceutical products and inhalation devices, for example, is enabling the company to meet the challenges posed by additional requests from the agency, Kesselring says. "We're able to help guide medical device companies that come to us and say, 'we've never had this question asked before.'"

Working with medical device clients involves compliance with various subsections of ISO 10993 that are associated with the chemical compatibility and chemical release aspects of the device. These aspects formally require gravimetric evaluation. However, FDA has been requesting information associated with more chemically specific means of testing using gas chromatography-mass spectroscopy (GC-MS), liquid chromatography-mass spectroscopy (LC-MS), and inductively coupled plasma mass spectrometry (ICP-MS). The company often works with a toxicologist to review the test results in order to confirm that no unsafe compounds or impurities are present, Kesselring notes.

In addition to regulatory challenges, such medical device testing can also present cost concerns, Kesselring adds. "For example, the costs associated with chemically specific evaluation of unknown compounds using GC-MS, LC-MS, and ICP-MS can be significantly different from previous budget amounts. A study can cost anywhere from $15,000 to $20,000 for a smaller study involving a few contact materials to over $100,000 for some projects." The cost depends on what FDA is expecting and the specific portion of the device to be tested, he adds.

Materials Testing

Combination products are hardly the only medical devices that must undergo extensive testing. Thus, the large number of orthopedic implant manufacturers coming to Sherry Laboratories (Daleville, IL) are looking to test materials in both raw and finished states, remarks Jennifer Tret, the company's vice president of materials testing. On the device side, for example, surgical-tool clients using the lab's services work with stainless steel and cobalt-chrome alloys that require routine mechanical testing for tensile strength, grain size, microstructure, and surface defects.

Most of the company's testing services involve heat qualification of bar stock or coated finished products at a quality assurance lab, Tret says. But for orthopedic components, it also employs cyclic dynamic and fatigue testing to determine how many cycles the material can withstand and how much quality load it can take.

Sherry Laboratories primarily uses ASTM test methods, starting with ASTM 466 through ASTM F-1854 to calculate tissue gradients. "ASTM F-1854 has just been created, and we've done some round-robin testing to help get it off the ground," Tret states. The end-user may specify the need to measure tensile strength, for example, while finished products may have specifications for coating thickness, porosity, and voids.

Test Plan Development

Included in Gilero Biomedical's range of testing services is force measurement testing of medical device components.

When people have a new idea and new products, they want to expedite time to market, which helps to minimize overall developmental costs. But manufacturers with innovative designs, Fentress notes, often face difficulty because the engineering work is not the only facet of the development process to consider. "There's a cost-prohibitive threshold that makes device design difficult," Fentress says.

Achieving this goal of minimizing time to market and development costs requires a rock-solid product-requirements document, Fentress adds. "Essentially, this document links the device users' needs to the specific engineering requirements of the device. Often customers have a good device idea, but they haven't yet hammered out what they really need the device to do. The way to minimize development time is to hammer those details down."

The product-requirements documents should also encompass test plan development. "Sometimes, test plan development can be a sanity check on product development itself," Fentress says. The customer might set the gravity flow rate of a new medical device at, say, 4 L/hr. That might be okay, but there's an international standard that says it should flow at 6 L/hr." In such cases, Gilero advises the manufacturer to meet the international standard. An efficient testing plan validates the product requirements.

Medical device customers often want to know how a new design feature could change the regulatory pathway, particularly with Class II filings for 510(k) clearance, Fentress remarks. By evaluating new products against predicate devices, however, customers may be able to get their products to market without performing clinical trials. This process doesn't have to be expensive or painful, Fentress adds. Often testing adjustments can take place within the time frame allotted for designing the device. "Maybe a different flow-rate test or burst test is all you need to do.

Pain Avoidance: Probing New Ways to Monitor Glucose

For millions of diabetes sufferers, pricking the skin to obtain a drop of blood to test glucose levels is uncomfortable at best and a potential cause of infection at worst. It's hardly surprising, therefore, that researchers are busily investigating alternative methods for testing glucose that do not rely on traditional lancets and pinpricks. Thus, while some research teams are focusing on such needleless methods as biosensors and chips to monitor glucose levels in a range of body fluids other than blood, others are striving to make needles as small and noninvasive as possible to minimize pain.

Considering the vast and growing scope of diabetes today, pinpricks are no small matter. Worldwide, one in 10 people are afflicted with the disease, according to the World Health Organization's World Health Statistics 2012 report. In the United States, diabetes afflicted 25.8 million in 2011, or 8.3% of the U.S. population. Behind these raw numbers stands a healthcare catastrophe in the making. Diabetes, according to the National Diabetes Fact Sheet, 2011, published by the Centers for Disease Control and Prevention, is the leading cause of kidney failure, nontraumatic lower-limb amputations, and new cases of blindness among U.S. adults. It is also a major cause of heart disease and stroke, ranking as the seventh leading cause of death. Such statistics underscore the importance of dilligent diabetes management, but it also couldn't hurt to eliminate the ouch factor from the process.

Multifluid Sensing Capability

SEM images show platinum-decorated graphene nanosheets that are key components of a new type of biosensor that can detect minute concentrations of glucose in saliva, tears, blood, and urine. (Image courtesy of Purdue University/Jeff Goecker)

Centered at Purdue University (West Lafayette, IN) and the Center for Biomolecular Science and Engineering at the U.S. Naval Research Laboratory (Washington, DC), a group of scientists involved with diabetes research have engineered a noninvasive, low-cost biosensor that could detect glucose in concentrations as low as 0.3 micromolar not only in blood, but also in urine, saliva, and tears.

"The nanostructured glucose biosensor works just like current-generation finger-prick blood glucose monitors do," explains Jonathan Claussen, a research assistant professor at the Naval Research Lab. "Namely, glucose oxidase interacts with glucose found within a biological sample such as blood." This interaction ultimately produces electrons that can be monitored on a digital readout. The generated electrical signal, Claussen adds, is subsequently calibrated to known glucose concentrations, enabling the researchers to correlate the digital readout to glucose concentrations even when the glucose concentration in the sample remains unknown.

The biosensor is constructed from layers of graphene nanosheets, platinum nanoparticles, and the enzyme glucose oxidase. The edges of each graphene layer have dangling, incomplete chemical bonds that attract the platinum nanoparticles. The combination of the graphene nanosheets and the platinum nanoparticles forms electrodes, which generate a signal when the glucose oxidase attaches to the platinum nanoparticles and converts glucose to hydrogen peroxide.

While this biosensor monitors glucose levels as do standard technologies, it works better, according to Claussen, because of the properties of the graphene and platinum nanoparticles. "These nanomaterials are highly electroactive on the nanoscale and have a very large surface area," he says. "Thus, the nanomaterials are able to funnel electrons from the glucose oxidase/glucose reaction more readily than conventional materials, making our biosensor more sensitive over a wider glucose concentration range than current glucose monitoring devices."

The biosensor's ability to monitor a range of body fluids is attributable to its wide sensing range, comments Anurag Kumar, a Purdue University doctoral student and member of Claussen's team. "What's unique about our technology is that this single sensor can detect glucose levels in different body fluids simultaneously. You don't need different sensors for different fluids." This capability, in turn, is rooted in the sensor's structure. "The sensor's nanosheets--2-D materials standing vertically on a flat substrate--lend the structure added dimensionality," Kumar says. "This dimensionality enables a very high density of platinum nanoparticles per unit area to form on top of the sensor, resulting in excellent sensing performance."

Growing the nanostructures on a silicon chip via chemical vapor deposition and then electrodepositing platinum nanoparticles on the graphene proved to be the most challenging fabrication step, Claussen notes. After these steps were accomplished through trial and error, the team was able to use glucose oxidase enzyme immobilization techniques to transform the nanostructured chip into an active glucose sensor.

But more work remains to be done before the technology is ready for commercialization. "Since our tests to date have not involved the use of actual biological samples, we hope to test the device in such fluids as blood and tears in a clinical trial setting going forward," Claussen states. "We predict that this type of testing and optimization will continue for another five to ten years before we have a finished product."

Monitoring Glucose Levels in Saliva

Like its colleagues at Purdue University and the U.S. Naval Research Laboratory, a team of researchers at Brown University (Providence, RI) is also developing a biochip that can measure glucose without relying on blood. Using plasmonic interferometers, assistant professor of engineering Domenico Pacifici and his team have engineered a technology that can detect glucose at levels similar to those found in human saliva.

"The concentration of glucose in saliva is about 100 times less than that in blood," remarks Vince Siu, a PhD candidate in biomedical engineering at Brown and a member of Professor Tayhas Palmore's group working in collaboration with Pacifici's team. "Our plasmonic interferometers are unique because they can be tuned and made more sensitive to very small concentrations of glucose."

One of the team's devices consists of a single slit about 100 nm wide etched between two 200-nm-wide grooves on a metal film, according to Siu. Incoming incident light hitting the surface of the chip is scattered at the grooves and interacts with the free electrons on the metal surface to create surface plasmon polaritons (SPPs), an electromagnetic wave with a wavelength smaller than a photon in free space. The SPP waves originating from the two grooves can interfere with the incident light going through the single slit, determining maxima and minima in the light intensity transmitted through the slit.

When an analyte such as glucose is present on the sensor surface, a relative phase difference occurs between the counterpropagating SPP waves, causing a measurable change in light intensity in real time. By etching thousands of plasmonic interferometers on top of a 1 × 1-cm biochip, each of which acts as its own detector, an array of thousands of plasmonic interferometers can be built, enabling the biochip to determine the fingerprints of the analytes, Siu explains. "Our plasmonic interferometers can be tuned to measure very low concentrations of analytes such as glucose in saliva by simply varying the distance between the slit and the two grooves on the chip."

Fabricating the biochip entails several steps. The first is to deposit a thin metallic layer on top of a transparent chip using E-beam deposition. The second involves etching nanostructures on top of the metallic surface using focused ion-beam milling. And the third requires forming a polydimethylsiloxane microfluidic channel to accommodate the flow of the analyte. The chip's optical setup consists of a broadband white-light source, a microscope, a charge-coupled-device camera, and a spectrograph.

"Detecting tiny but clinically relevant concentrations of a molecule such as glucose in saliva was challenging," Siu comments. "We had to fine-tune the optical setup and the plasmonic interferometers to achieve this goal. To tune the device, the team characterized and modeled the optical response of hundreds of plasmonic interferometers by varying the distance between the slit and the two grooves, selecting the devices that demonstrated the best interference response for the sensing purpose.

While a positive correlation has been demonstrated between blood glucose and salivary glucose levels, a standard method of measuring salivary glucose has yet to be achieved. Nevertheless, because the plasmonic interferometers are sensitive enough to measure glucose in saliva in real time, the Brown researchers hope that they will be able to determine a more-accurate time-course correlation between blood glucose and salivary glucose levels.

Microneedles Detect Blood Glucose

A scanning electron micrograph shows a single microneedle equipped with a sensor used to detect compounds such as blood glucose. (Image courtesy of Talanta)

In contrast to the research under way at Purdue, the U.S. Naval Research Lab, and Brown, researchers at North Carolina State University (NC State; Raleigh), Sandia National Laboratories (Albuquerque, NM), and the University of California at San Diego (La Jolla, CA) are developing a diabetes-treatment technology based on microneedles. If successful, their effort could result in a painless or low-pain mechanism for sensing glucose levels and delivering insulin.

While several previous efforts have aimed at the development of a microneedle technology for monitoring glucose, these efforts involved devices in which the microneedles and the sensors were separated by channels. "Our innovation is that we have the sensing element at the tip of the microneedle," explains Roger Narayan, a professor at NC State. "By putting the sensing component at the tip, you don't have to worry about biofouling of channels within a microfluidic device, which could be a big problem for microneedle-based sensors that one would like to use for some period of time," he adds.

The researchers use two different rapid prototyping methods to create their microneedles: digital micromirror device-based stereolithography and two-photon polymerization. While both methods involve performing selective polymerization of a liquid resin, the former technique produces structures with a substantially higher throughput. In addition, the researchers are evaluating new classes of materials to fabricate microneedles, Narayan says.

Optimistic about the technology's potential clinical applications, the research team envisions that the microneedles could eventually be incorporated into a wearable device resembling a wristwatch to continuously monitor insulin and other compounds in the blood. In such applications, the device would integrate several components, including a skin interface, a sensor, and a delivery system. To that end, the researchers are actively partnering with several companies to work on commercializing the technology.

Looking further toward the future, Narayan and his colleagues imagine that the microneedles could be bundled together with sensors and pumps to create a minimally invasive wearable artificial pancreas. For example, the microneedles could be equipped with a variety of sensors for detecting glucose and other chemicals in the blood, including pH and lactate.

While microneedles for use as drug-delivery devices are starting to reach the market, work remains to be done on the devices' sensing component. "I think it will take a little bit more time to commercialize microneedle-based sensors because improvements in biocompatibility at the skin-device interface are needed if you want to have continuous monitoring at the skin's surface," Narayan comments. "If you are using something as just a replacement for a hypodermic needle, you don't have to worry about the long-term biocompatibility, whereas if you want a sensor to interact with the skin for a while, improving the tissue-material interface will become really important."

Advanced Medical Materials to Contribute to Improved Prostheses

A team of researchers at the Georgia Institute of Technology (Georgia Tech; Atlanta) and Florida State University (Tallahassee) have been awarded a $4.4 million contract to engineer an improved prosthetic socket system to improve the lives of veteran amputees. As part of the project, the researchers will focus on developing innovative adaptive materials that are better able to handle changes in limb volume and pressure while providing active cooling and temperature control. In addition, they will design the new socket system and evaluate advanced manufacturing technologies.

"This transformative project will leverage the latest advances in innovative materials and advanced manufacturing technologies to build the next-generation prosthetic socket system with significantly improved comfort," remarks Ben Wang, a professor in the Stewart School of Industrial and Systems Engineering and the executive director of the Georgia Tech Manufacturing Institute.

"Despite the advances made in prosthetics over the years, the socket continues to be a major source of discomfort for our amputees due to issues arising from poor fit, elevated temperatures and moisture accumulation," adds Changchun (Chad) Zeng, a Florida A&M University-FSU College of Engineering assistant professor and principal investigator on the project. "These adverse conditions effectively limit the basic activities of amputees and can greatly diminish their quality of life. This award gives us the opportunity to tackle those problems so our veteran amputees can live better, more fulfilling lives."

By integrating such advanced materials as composites and nanomaterials and by implementing such new manufacturing technologies as additive manufacturing and printed electronics, the team hopes to create a next-generation prosthetic device that offers significantly improved comfort. While the first phase of the project will focus on developing and testing technologies for the individual socket components, the second will optimize each system, refine the materials, and produce prototypes.

For more articles on medical device materials, go to:

Medical Materials

New Medical Device Polymer System Is a Jack of All Trades

Bioabsorbable Magnesium Provides Temporary Strength and Stiffness to Next-Gen Orthopedic Implants

Discovery of Tribofilm Lubricant Could Help Improve All-Metal Hip Implants