Medical Device Link.

Originally Published EMDM March/April 2003

Regional Focus

The northern town of Aalborg is wooing medical technology companies with an emphasis on biomedical engineering at the university, leading-edge research at the university hospital, and a tradition of innovation in telecommunications.

Baden-Württemberg, Modena, Galway . . . Aalborg? Denmark’s fourth-largest city is not yet one of Europe’s medical technology hubs, but give it time. Civic leaders, entrepreneurs, academics, and medical professionals have been diligently laying the groundwork to put Aalborg and the surrounding region on the med-tech map.

Aalborg boasts the only university in Europe to offer a biomedical engineering curriculum that stretches from the bachelor’s to doctorate level. The city’s hospital was recently granted university hospital status, expanding its research capabilities. Clinical and academic researchers can interact with potential industry partners at the HealthnTech Research Center. And the region’s rich industrial past in the electronics and telecommunications sectors ensures that a wealth of resources can be applied to e-health products. RTX Healthcare, a subsidiary of RTX Telecom that is dedicated to integrating wireless technology into medical devices, is showing the way.

While a number of start-up companies have set up shop, many of them university spin-offs, a vast influx of medical technology companies has not occurred. Local officials concede that the region has yet to reach critical mass in the number of healthcare manufacturers. They are confident, however, that a well-educated workforce and focused infrastructure will put Aalborg on device OEMs’ radar screens.

Building a Knowledge Base

“Our research shows that an industrial environment with access to top-notch university research and skilled employees will attract companies,” says Charlotte Villadsen, who heads the industrial liaisons office at the university. She points to a benchmark study published by IBM Business Consulting Services in March 2003. It concluded that for medical technology–related R&D, “North Jutland offers the lowest cost at a more than acceptable level of quality compared with Dublin, Berlin, Munich, and Cambridge.” That validates the region’s approach, says Egon Toft, who heads the HealthnTech initiative. “From the beginning, a cornerstone of our strategy has been to build an education system that will produce a knowledgeable workforce. Had we failed with the students, there would have been no point going any further in this direction,” says Toft. 

The department of health science and technology at Aalborg University has attained international recognition in such disciplines as motor control and neurorehabilitation technology, sensory systems and technology, medical informatics, and stem cell research. Founded in 1974, the university opted for a multidisciplinary team-based approach to its curriculum. “Problem-based teamwork has always been part of the curriculum,” says Villadsen, who is a graduate of the school. This approach has been understandably popular with industry, which prizes “graduates’ ability to solve real-world industrial problems,” she adds.

The recently established master’s programme in biomedical engineering will send approximately 50 graduates per year into the workforce. The doctoral school educates students at an international level—the PhD programme is in English and half of the students are foreign. Within the department of health science and technology, the Center for Sensory-Motor Interaction (SMI) applies an interdisciplinary approach to leading-edge research.

Simply put, “we tap into the nervous system to decode neural traffic and, ultimately, manipulate it,” says SMI head Thomas Sinkjaer. The goal is to restore lost motor function in patients by means of a closed-loop system that mimics natural movement. Three interrelated areas—sensory systems, motor control, and rehabilitation technology—are the focus of study in the department’s various laboratories. 

One activity involves the use of electrodes to develop neuroelectrical interfaces that will stimulate excitable tissues and record the interactions. At the SMI’s motor control lab, new techniques are under development to refine knowledge of how humans control the movement of their bodies. 

A natural extension of this line of study can be found in the laboratory for rehabilitation technology, which is focused on the development of neural prosthetic devices. The natural sensory signal is captured by a recording electrode, amplified and processed, and then used as feedback for a controller that acts on a stimulator to activate the paralyzed muscles. This research has led to new prospects in implantable rehabilitation technology, according to Sinkjaer.

The centre also houses laboratories devoted to pain research, biomechanics, and brain mapping and cortical imaging. “Our research at SMI has spawned some interesting spin-off companies,” notes Sinkjaer. “One of them, Neurodan (Aalborg) is on the verge of bringing its first products to market.”

Neurodan’s stated mission is the commercialization of electrical neurorehabilitation technology products for patients with central nervous system disorders. The company’s ActiGrip system is an external device designed to restore hand and grip functions to stroke victims by, in essence, retraining the brain. The firm has also developed an implantable stimulation device for patients with drop foot, a condition that affects cerebral stroke victims. 

Technology developed at SMI also has been applied by NeuroCon (Aalborg) to develop a device that manages incontinence. The implanted product detects and prevents bladder contractions by mimicking a state of arousal. “Thankfully, you can’t empty your bladder when you are aroused,” says Sinkjaer. Some patients are quite enamoured of the product, he adds.

The center has only skimmed the surface of the technology’s potential, says Sinkjaer. “If you have the technology available to listen to the neural traffic and act on it, many applications are possible.” But there are multiple challenges, as well.

“If you think of the neural network as a phone cable, we can hear talking, but we can’t reliably distinguish who is talking to whom.” To refine this ability, work is being conducted at SMI on a new family of electrodes, including some on the nano scale, that will enable next-generation interfaces. 

Partnering with Industry

The HealthnTech Research Center, a collaborative venture between Aalborg University and Aalborg Hospital, is designed to support biomedical research and to encourage industry to develop products based on these technologies. As a professor at the university as well as an acting physician at the hospital, Toft is uniquely well suited to head the centre. When I met with him, he was quite excited at the imminent prospect of inheriting 4500 sq m within the hospital for biomedical research.

“The nursing school, which currently occupies the space, is moving to a new campus,” says Toft. “We will turn that into the most important research centre in the hospital for medical and health technology students. It will also include office space, which can be very convenient for firms engaging in clinical studies,” he says. More importantly, adds Toft, it will provide students with an opportunity to tackle real-life problems. “The students may not find a solution,” he says, “but it is a great opportunity for companies to use our resources to determine whether a particular technique is worth pursuing.” The centre should be ready by 1 September, adds Toft.

Toft sees a bright future for Aalborg’s budding medical technology cluster. “It’s important to remember, he notes, “that a cluster can be focused in particular disciplines. It does not need to encompass the totality of medical technology.” For example, the region’s telecommunications industry, which employed 8000 people in its heyday, can be a dynamic force in developing new healthcare products. RTX Healthcare is a prime example.

A Wireless World

The Telehealth Gateway from RTX Healthcare wirelessly collects and transmits medical data to a remote server via the Internet. Intended for the home-care market, the product is marketed to device OEMs and system integrators.

Located in the outskirts of Aalborg in Noerresundby, RTX Telecom has experienced unbridled growth since it was founded in 1993. A supplier of electronics and wireless technology to many multinational OEMs, the company currently employs approximately 230 people, more than half of whom are development engineers. In 2001, the firm acquired Penell a/s, which had established a worldwide reputation in the development of wireless capabilities for medical equipment. (Penell notably developed a Bluetooth-enabled pulse oximeter in collaboration with US-based Nonin Medical. The device is poised to go into production; it is currently available as an OEM product.) 

Penell changed its name to RTX Healthcare in October 2003 to stress that “we are a subsidiary of RTX Telecom focused on providing wireless connectivity technology to medical device manufacturers worldwide,” says marketing manager Jens Kofoed. It recently launched a line of diagnostic products for home-care use that incorporate leading-edge wireless connectivity and secure data transmission capabilities.

The wireless weight scale, blood pressure monitor, and associated Telehealth Gateway represent a “step up in the value chain for the company,” notes Kofoed. In the past, the company has followed a traditional outsourcing model by supplying electronics and subassembly design services to device manufacturers. This new line of products takes that business model in a new direction. The company now obtains a technology in the form of basic devices, integrates wireless e-health capabilities, obtains the necessary product approvals, and markets the system as an OEM product to device firms and system integrators. The firm’s underlying communications platform, which supports Bluetooth, GSM/GPRS, and LAN protocols, will also be offered for integration with other devices.

“One of the key features of the [home-care diagnostic] system is its simplicity,” says engineering manager Niels Ole Andersen. “The user makes no adjustments to the system. The devices and the Gateway are configured prior to shipment. All the patient needs to do is plug it into a power source and a phone line,” explains Andersen.

The company has spared no effort in ensuring that data security complies with US HIPAA and international guidelines, notes Andersen. Data are encrypted using the Secure Socket Layer protocol, which is implemented in the company’s proprietary Callisto software platform that is part of the Gateway system. Callisto also supports authentication on the client and server ends, and configuration options can be hidden behind two levels of user names and passwords. None of this will be visible to the patient, who sees only a box adorned with a light-emitting diode to indicate that the device is working. “The data are delivered in XML,” adds Andersen, which gives the manufacturer maximum flexibility in designing the information display.

The price point is substantially lower than existing products that perform a similar function, according to the firm. A complete system that wirelessly monitors a patient’s weight and blood pressure and transmits the data to a remote database can be marketed for under US$1000, says Kofoed.
“When OEMs see this technology, they immediately begin thinking about a whole range of other applications,” says Kofoed. Indeed, several other medical devices that apply this technology are in RTX Healthcare’s pipeline. 

For instance, “there are a lot of potential wireless applications that simply involve capturing information,” notes Andersen. He sees home care and its enabling technologies as a market that is on the verge of exploding, and it’s a wave that RTX Healthcare is well-equipped to ride, he adds. “We have the experience, knowledge base, and capabilities to meet the anticipated demand for high-volume products that comply with global regulatory standards.”

Establishing Contact

To learn more about medical technology initiatives in greater Aalborg, the most convenient first point of contact is Charlotte Villadsen at the university’s industrial liaison office: cvi@adm.aau.dk. The HealthnTech Research Center’s Web site can be found at www.healthntech.dk.  Information about the Center for Sensory-Motor Interaction can be found at www.smi.auc.dk; to learn more about the department of health science and technology in general, go to www.hst.auc.dk. 

A sampling of suppliers from Northern Denmark and other parts of the country are profiled on the following pages of this section. Additional Danish companies providing products and services to medical device OEMs can be sourced in our on-line database at www.devicelink.com.  

Søbygaard Machine Design ApS

From his home office and small workshop in Naestved, Henrik Søbygaard has achieved a rather remarkable global reputation as a designer of medical device production equipment. From fully automated in-line catheter production systems to straightforward manual tooling, his equipment can be found in the United States, Germany, the Middle East, China, and points in between. “My customers are looking for reliable equipment at reasonable prices, and that’s what I provide,” says the managing director of Søbygaard Machine Design ApS. 

One of the ways in which he keeps costs down while maintaining a leading-edge reputation is, paradoxically, by not investing in capital equipment. Explains Søbygaard, “If I have a milling machine, for example, I have to use it to amortize the investment. Instead, I work with specialized outside suppliers that invest in the latest technologies. By not tying up my money in equipment, I can offer my customers better prices.”

Before going into business on his own, Søbygaard worked as technical manager at Uno Plast, where he supervised the company’s transition to an automated production line. His passion remains fully automated equipment, but Søbygaard also derives great satisfaction from supplying machines to emerging economies, where the demand tends to be for manual equipment. “Denmark is a small country, and I like to help other small countries to develop their industry,” he says. At the other end of the spectrum, Søbygaard built the first automated catheter assembly line for Medline in the United States.

In addition to custom equipment, Søbygaard has several machines that can be purchased off the shelf. A tip trimmer designed to produce a smooth rounded outer tip on suction catheters attains a throughput of 1000–1200 units per hour. It is suited for use with soft tubing in sizes from CH 5 to CH 40. A device for forming closed, open, or curved thermoplastic catheter tips is also available; it achieves production speeds of 500–800 units per hour. 

In addition, the company has developed catheter-eye-punching tools, which are mounted on a pneumatically controlled punching press operated by a foot pedal. All the equipment is designed for cleanroom use.

Soltech Technical Solutions

Einar Gjaldbaek Petersen is the quintessential engineer. Managing director of Soltech Technical Solutions (Maaloev), Petersen welcomes challenging projects and loves to tinker. What he does not enjoy is endless repetition. For example, his company has developed tip-forming and bonding equipment for a major supplier of medical tubing, a potentially lucrative field. “Some people have started up companies that exclusively manufacture this type of equipment, and they have done extremely well. I know it makes sense to specialize,” sighs Petersen, “but that’s just not me.” His passion is product development, prototyping, and building the machinery necessary to successfully produce the part. He relishes conversing with end-users to identify problems they encounter in their professional lives and devising a solution that makes economic sense. “Design for manufacturability is foremost on my mind, even as we are working on a prototype. Simplicity and cost-effectiveness are my goals.” His newest product—a device that cuts soft tubing while simultaneously producing rounded edges in the inner and outer diameters—is a perfect illustration.

On its face, it’s a very simple component, “but getting it to work properly with soft tubing was nerve-wracking,” says Petersen. “Manufacturers typically use heat to round tubing edges, but that process takes four times longer than using my tool.” The small metal part (pictured on page 76) can be integrated into production equipment or used manually. Based on early industry feedback, Petersen figures he has a hit.

Soltech processes metal and plastic materials to develop disposable, implantable, and combination products. “We routinely work with titanium, stainless steel, and nickel titanium, to name a few materials commonly used in the medical arena,” notes Petersen. Specific products and associated tooling the firm has developed range from a component used in kidney removal procedures to neurology implants and stent introducers.

The company has a battery of CNC and manual turning machines; milling, tip-forming, and bonding equipment; and coilers on-site, as well as extensive testing equipment. If a project requires specialized production equipment, Soltech often can build it, notes Petersen. 

RTX Healthcare

Improving a patient’s quality of life while reducing overall treatment costs could be considered the Holy Grail of the medical device industry. RTX Healthcare (Noerresundby) believes that integrating wireless communications capabilities with medical diagnostic equipment is a meaningful step in that direction.

RTX Healthcare is a subsidiary of RTX Telecom, which has expanded tremendously since it was founded in 1993. On the telecommunications side of the business, the firm has completed more than 300 projects, developing everything from chip sets to finished products for global OEMs. RTX Healthcare (formerly Penell a/s) is dedicated to using its considerable resources in wireless connectivity to benefit medical products. “We feel that the healthcare market is immature in this regard,” says marketing manager Jens Kofoed, “and our mission is to make medical devices wireless worldwide.” The introduction of a family of OEM home-care products that incorporate Bluetooth technology represents the most recent milestone in this campaign.

The system’s core components are devices that measure blood pressure and weight, and a Telehealth Gateway unit that collects and transmits the data to a remote server via the Internet. All of this is performed wirelessly. The system is described as foolproof for the patient and surprisingly cost-effective. (See the feature article at the beginning of this section to learn more about this product.) The underlying technology platform, based on proprietary software, is also available for integration into existing medical equipment, and the company continues to offer a range of outsourcing services to the device industry, from product development to delivery of the finished devices.

One of the strengths of RTX Healthcare, notes Kofoed, is that it is not limited to one wireless technology. “Our development engineers have mastered all existing techniques,” he says. Moreover, the firm has developed a number of medical-related wireless platforms that can greatly accelerate time to market for new projects, adds Kofoed, and it has amassed significant experience resolving regulatory issues in the United States and Europe.

Danbridge a/s

Although it has established an enviable reputation for its component-testing equipment, the real strength of Danbridge a/s (Farum) resides in its knowledge base, says sales director Max Watson. When all is said and done, “ there are many companies that can develop testing equipment. Danbridge was founded in 1949, and our people have seen it all . . . they know everything there is to know about the problems that can crop up,” says Watson. The company doesn’t just sell a box, he stresses. “Setup, training, and maintenance are all part of the package. Some of our customers send back the equipment every 12 months for recalibration,” he adds. Reliability, in other words, is a core value at Danbridge, which is especially appreciated by the firm’s medical device customers.

The company has developed nondestructive high-voltage dc testers that are increasingly used to verify the insulation in endoscopes used to burn cancerous tissue. The procedure started in Sweden and is expanding throughout Europe. “It is, of course, extremely important that the current is exactly what it should be and that there are no cracks in the insulation,” says Watson. The JP30 A tester is a mains-operated 30-kV stationary-use unit suited for benchtop use in laboratories and production and quality control departments. An effective-current-limit circuit ensures safe operation despite the high voltage. An active LP filter with an integrated audio amplifier feeds a built-in loudspeaker to provide audible ionization alerts.

The firm also offers a third-harmonic tester that is reportedly the only product of its kind for high-speed applications. Used to test the reliability of passive components, the CLT10 applies a pure 10-kHz signal to the component or material and evaluates the third harmonics caused by defects and nonlinearity. Distortions as low as –160 dB can be detected, making it possible to spot defects that escape notice in conventional tests. The instrument can be integrated into high-speed production lines or used in benchtop applications.

Ferroperm

“To be competitive, Danish companies have no alternative but to emphasize quality,” says Torsten Bove, technical director at Ferroperm Piezoceramics (Kvistgaard), which produces piezoelectric ceramic parts for custom applications. “Labour is expensive and we have few natural resources, so we promote our products based on superior stability, better aging, and reproducibility.” The company places special emphasis on the reproducibility of its products’ properties and parameters. Typical variations in batch-to-batch material parameters are within ±3–5% over several years of production. “We have reams of documentation tracking each step of the production process. It involves more than 20 steps, and we know exactly what happens at each one.” Ferroperm also has its eye on the future. The firm recently developed high-intensity focused ultrasound (HIFU) materials that combine diagnostic and therapeutic applications. Procedures that will benefit from this technology include the treatment of tumours.

The Pz50 family of materials are characterized by high permittivity and mechanical Qm values along with low dielectric losses. The materials’ specific temperature range—between room temperature and a maximum 80°C—and elevated power are critical to their use in the treatment of cancerous cells, explains Bove. “Because they are young cells, they are less resistant to heat than healthy ones,” he says. Traditional materials can be used in the rapidly developing field of ultrasound-assisted surgery and therapeutics, adds Bove, but HIFU piezoelectric materials offer a more focused alternative. “To the best of my knowledge, we are the only company offering a new material that has been optimized for this application.”

As with all of the company’s products, Pz50 materials can be manufactured to suit customer specifications. The firm has the production capabilities to design and manufacture focusing bowls and special electrodes.

The company also supplies hard PZT products for therapeutic transducers and dental cleaners, a soft piezoceramic for medical imaging system arrays, and a modified lead titanate that features high anisotropy and a small grain size for single-element transducers.

Danfoss Tantalum Technologies

Tantalum is a biologically inert material that exhibits greater corrosion resistance than titanium. It has also been suggested that tantalum has a higher bone in-growth rate than titanium. However, solid tantalum’s high density and limited strength make the material unsuitable for use in load-bearing implants. A recently developed method for depositing a thin layer of tantalum on surgical-grade stainless steel and CoCrMo alloy substrates shows immense promise for that application.

Studies commissioned by Danfoss Tantalum Technologies (Lyngby) found that a 20-µm layer of tantalum prevents dissolution of ions from the substrate and maintains a surface composition complying with surgical-grade unalloyed tantalum. In addition, bending fatigue strength can increase as much as 60% while the tensile strength and elongation of the substrate are unaffected. It is also very interesting to note that when breakage is induced the coating and substrate act as a homogenous material, says Søren Eriksen, who manages one of the company’s coating facilities on the grounds of the Technical University of Denmark. There are no observable cracks in the surface layer or substrate-and-tantalum interface prior to failure. Overall test results show that a high-strength substrate with a tantalum coating could be suited for use on load-bearing implants, he notes.

“We currently have a coated hip implant in a preclinical study,” says Eriksen, “and we have done early-stage studies on dental, fracture, and spinal fixation devices.” Material studies have been extremely encouraging, he notes. “We can combine the mechanical properties of substrates such as surgical-grade stainless steel and CoCrMo alloys with the corrosion resistance of tantalum.” For example, stainless steel will not withstand exposure to hydrochloric acid at 75°C, says Eriksen. “But when the material is coated with tantalum, it passes the test. The coating is free of pinholes, which is very difficult to achieve with other coating materials. And the coating actually improves the fatigue strength of CoCrMo from 600 to 840 N/mm2, a result that frankly took us by surprise,” he adds. The company also reports that the application of a tantalum coating improves the biocompatibility of the substrate to a level superior to that of titanium.

The company believes that these results will prompt device manufacturers to consider the use of tantalum-coated materials for a number of load-bearing implants. This process may enable device OEMs to source materials for nonactive implants based on their machinability, because biocompatibility can be conferred by means of a tantalum coating after shaping. A cost reduction may ensue.

The company’s business plan is to offer surface treatment on a contract basis and to develop devices that benefit from this process. Danfoss Tantalum Technologies is actively seeking partners to collaborate on development projects.

Pinol a/s

Precision mechanical parts measuring 0.15 to 2 mm diam are fabricated by a company that also offers assembly, packaging, and labelling services to the medical, dental, and electronics industries. Pinol a/s (Gørløse) is certified to ISO 9001:2000 and ISO 14001, and it expects to achieve ISO 13485:2003 certification in the early part of this year.

To help device OEMs get products to market rapidly while minimizing costs, the company offers the services of a development engineer. He or she can help to optimize processes from the design and development stage to serial production of the device.

The company’s production capabilities include turning, milling, grinding, laser cutting and welding, laser marking, surface treatment, cleaning, assembly, and packaging.

Linak a/s

A four-part telescopic lifting column suited for hospital beds and a parallel drive system for beds with two lifting columns have been introduced. Linak a/s (Nordborg) presented the products at the Medica trade show in Düsseldorf, Germany, in November.

Requiring only 350 mm of installation space, the BL4 column provides a long stroke length in confined areas. Although the actuator boasts a maximum stroke length of 400 mm, the individual columns have sufficient overlap to ensure stability. The column’s maximum load is 2200 N under static conditions and 1600 N dynamic. Extension speed is 13 mm/sec with a 90-kg load.

The firm’s parallel drive system incorporates a new concept to control dual actuators and columns. The None Reed Parallel (NRP) technology does not rely on a microprocessor to control beds with two lifting columns. Instead, NRP is based on analogue and speed controls, which may result in a cost reduction for OEMs.

Melitek

Plasticizer-free polyolefin-based elastomers that feature properties similar to PVC are increasingly being specified for use with infusion sets and catheters, according to a firm. Tubing made from Meliflex polymers also exhibits properties suitable for peristaltic pump applications, reports materials supplier Melitek (Hellerup). The material is transparent, flexible, and kink resistant, and its water vapour and chemical resistance properties are superior to PVC, according to the company. Strategic applications include blood transfer, dialysis, drug-delivery, and catheter systems.

The elastomers are available in various degrees of hardness and flexibility. They can undergo heat-sealing operations at low temperatures. Compliant with USP Class VI guidelines, the Meliflex materials withstand 121°C sterilization temperatures and are compatible with EtO, gamma, and E-beam methods. They can be solvent-bonded with ABS, acrylics, polycarbonates, PVC, and other materials.

Product Release Europe ApS

Colleagues were prone to snickering when Product Release Europe ApS (Kvistgaard) announced plans to build a cleanroom with a highly sophisticated robotic system to coat guidewires. “A company that was having hydrophilic coatings applied in the United States asked us if we could perform that service in Denmark,” says Morten Saabye, chief technical officer. “We figured we could do it at a competitive price if we could automate the process as much as possible.” The facility, dubbed the Men-in-Black compound because its shabby exterior conceals a state-of-the-art robotic coating line, began operation last summer.

“The only human intervention involves the placement and removal of the guidewires,” says Saabye. The components are attached to fixtures on an overhead conveyor. A robot grips the fixtures, dips the guidewires in a series of solutions, and places them in an oven. Once they have been cured, an operator removes and packages the coated products. The process can be adapted to dip coating needles, says Saabye, something the company is already investigating. “The skeptics have been proven wrong,” Saabye notes with some satisfaction.

The family-run company began supplying coating services to medical device OEMs approximately 15 years ago, when Saabye’s father began offering PTFE coatings to guidewire manufacturers. A current growth sector for the company involves coating needles to provide electrical insulation for low- and high-voltage applications, such as EMG needles that measure resistance in muscle tissue. “The coating must be absolutely pinhole free,” says Saabye, “to prevent the electrical current from leaking out.” Product Release is planning to kick off a more durable PTFE coating with polyester that can withstand as much as 4000 V. “The makers of needles can produce nice tips and mount electrodes, but they also want to add value with a coating, and that’s where we come in.”

Product Release is the only company in the world to offer contract services using lubricious, hydrophilic, and drug-eluting coatings developed by US-based STS Biopolymers. As the new automated cleanroom suggests, “hydrophilic coatings are an evolving business. For example, we can put a hydrophilic coating on part of a guidewire and deposit a PTFE coating on the remainder,” says Saabye. “The customer gets a finished product without having to go through two surface-treatment suppliers.” 

Copyright ©2004 European Medical Device Manufacturer