DUSSELDORF, Germany — Two exhibition halls sitting literally upstream from the 16 halls of product displays at the sprawling Medica show here last week were dedicated to future product developments.
Called CompaMed, a companion show to the main Medica exposition, the exhibits featured materials such as polymers, metals or filters, as well as cables, lenses, pumps and plastic housings for future medical devices, and included the packaging, sterile and otherwise, that would hold them.
One of the two upstream halls was organized as a pavilion for IVAM (Dortmund, Germany), an international association of companies in the field of microtechnology, nanotechnology and advanced materials. Although the association speaks with a heavy German accent, it groups 242 member companies and institutes from 17 countries.
The group's managing director, Dr. Uwe Kleinkes, said micro- and nanotechnologies are the dominate theme for displays in members' booths, "because the mega-trend for the industry is making things smaller."
He added, "Nanotechnology was the hype a few years ago, and now we are well passed this hype and deep into the upstream development of the products using these technologies."
The industry is following the classic curve in hype, he said, promoted by the Gartner consultancy that shows public awareness and excitement for a new technology tending to peak several years before the technology actually comes to market. Thus, the smart investor waits until the hype-wave passes, typically years later, when there is convincing proof of concept and the technology begins to mature.
"Nanotechnology is just coming to maturity now," Kleinkes said. "Or I think of microfluidics, [which] we heard a lot about five years ago, and looking around this year's exhibits you can see the real micropumps are now here."
The good news, he said, is that innovations driven by these technologies have arrived, "but the bad news is that it still takes up to 10 years to build the products, and it takes patient investors."
Kleinkes offered two examples from German companies in the IVAM pavilion to illustrate his point: a finished product that revolutionizes inhalation therapy from PARIpharma (Munich), and a breakthrough technology for fluid dynamics from Bartels Microtechnik (Dortmund) that is still far upstream the market.
Nebulizers are inhalation devices used to deliver drugs to the airways of people with respiratory diseases, and devices from PARIpharma can credibly be called the industry gold standard for clinical trials with a deep database of past trials for researchers to reference, and PARI devices are recommended with sales of therapies from AstraZeneca, Novartis, Genentech and Sepracor.
"But this [nebulizer] technology is 50 years old," said Roland Stangl, the company's director of microtechnologies, adding that there is a heavy compressor that makes noises and vibrates, it uses a pressurized air to push the drugs, you need to plug it into the wall, and this keeps people stuck at home for their twice-daily treatments.
"Ten years ago we started developing this technology," he said, holding up the eFlowRapid, a hand-held inhalation device running on four AA batteries that gently and silently emits a vapor.
Now portable, people suffering from chronic respiratory conditions can carry it to the office, "and most important for our customers, it is much, much faster."
Using the traditional pressurized air delivery device, a treatment with a single drug take 20 minutes, he said. Most patients require three medications, spending more than an hour breathing in the medications.
The eFlowRapid delivers the medication in six minutes using traditional formulations, and with new formulations developed specifically for the device, a single session requires only two minutes.
The new nebulizer uses a membrane perforated with 3,000 laser-drilled holes that is vibrated at high frequencies in a resonant "bending" mode to yield high particle output rates.
"This is an advantage for fragile molecules like peptides and proteins used for new drugs being developed where if you apply a sheer force you risk breaking them up and the target compound will not be active," Stangl said.
He said that in less than two years eFlowRapid, which sells for 1600 ($906), has captured a 50% share of cystic fibrosis patients and is reimbursed in major markets of Europe, including Germany, the UK, France, the Benelux countries, Austria, France and Switzerland. PARIpharma is awaiting decisions on reimbursement in Italy and Spain.
The device was cleared for use in the U.S. in 2004 and is protected by 30 patent families.
Future applications for the device include clinical trials for pharmaceutical companies developing new formulations and compounds, new applications for asthma for children from 6 months to 10 years, "and chronic obstructed pulmonary disease is always a candidate," according to Stangl.
The star of the show at CompaMED for Bartels Microtechnik was a double actuator micropump, a mere 3 mm thick, capable of 500 micron-bars of pressure that the company demonstrated for the first time.
Heading further upstream for product development, Dr. Ulrike Michelsen pointed to a case where water was trickling over two identical slides, on the left bunching in groups and running down erratically like rain on a windshield while on the slide to the right the rivets ran smoothly along.
"Electricity," she said. "No chemical to break the surface tension."
Welcome to electro-wetting, a technology that one day could sort and treat body fluids on a point-of-care diagnostic test.
Think of the drops of water left on a glass coffee table as you lift your glass. Then imagine these drops splitting into seven symmetrical rows and moving to the other end of the table by an unseen force.
Here the glass coffee table is reduced to the size of a glass microscope slide, the drops of water become micron-sized droplets, and the mysterious force is electricity at a voltage so low the string of zeros in front of the number one would run off the life-sized glass table.
"We are working on fluid handling in the micro-dimension," said Michelsen. "The newest thing is this technique for transporting fluids by electro-wetting where the surface tension can be affected by an electric field and this force can actually move a micro droplet from one location to another on a free surface." In other words, a lab-on-a-chip surface that is not engraved with channels but is smooth as the glass coffee table top.
"For any diagnostic lab-on-a-chip, some type of force is needed to move the fluid," she said. Capillary action caused by micron-thin variations in channels carved into polymer plates is a now-common technology in this still developing field. Micro pumps are another force.
A third force, electricity, can be applied using micron-sized electrodes that work like traffic signals to make the liquid stop or move.
"More than that, electro-wetting can strip off sample droplets from a central reservoir for specific pathways, moving them through processes, mixing samples with reagents and then producing a result for diagnosis," Michelsen said.
The electrodes can be programmed in sequences, she said, to change the flow velocity of the droplets, the size of the drops and depending on the liquids chosen, the viscosity ratio.
The display of sample glass slides with embedded micro electrodes at the Bartels booth was startlingly similar to the look of computer processor chips, but instead of processing digitized data, the electrodes process serums and body fluids to give a result such as a binary yes-or-no for colorectal cancer, or a read-out for the quantity of white blood cells.