A recent Nanosensors KTN seminar held at the National Physical Laboratory in Teddington provided an opportunity to show how biotech, nanotechnology and electronics are being combined in a new generation of portable instruments. Dion Klunder, a scientist at Philips Research, described the trade-offs that go into taking a technology that uses small particles and putting it into something that can be used in the field.
Although the original plan was to use the Magnotech system as a drug detector that could be used by police in the same way they would use a breathaliser, the emphasis has switched at Philips to speeding up the diagnosis of medical conditions, kicking off with heart attacks. Bedside staff can use instruments like that to work out quickly what treatment the patient needs.
“If possible, you want to stratify patients in the ambulance,” said Klunder. “In that way you can enable minimally invasive medicine.”
The reality today is that it takes a while to get the results back from a central laboratory. Although the actual tests are quick, the delay lies in the amount of time it takes to get the sample there and the result back, on top of the time that a sample may have to wait before being processed.
“Even with a mild myocardial infarction, they [doctors] want the result in 20 minutes or less,” said Klunder.
The test for damage to a heart is well understood. When the muscle cells in the heart wall die they release some of the protein that makes up the muscle into the bloodstream. One of these protein components is troponin. Using antibodies that bind to troponin, it’s relatively straightforward to measure levels in a blood sample. The Philips technique moves that test from a laboratory environment to a handheld unit and a cartridge that contains a fluid chamber and the antibody.
Philips’ Magnotech system attaches the sensing antibody to magnetic beads — large in nanotechnology terms at 0.5µm across but that helps — so that they stick to molecules of troponin in the bloodstream. The magnetic beads are then attracted to the surface of the glass cartridge by a magnetic field generated by the instrument. This surface is coated with a second antibody designed to stick to a different part of the protein, if it’s present.
After a couple of minutes, to give time for enough of the antibodies to stick, the instrument reverses the magnetic field and any beads that do not have bound protein move away from the surface.
Rather than sense the presence of the beads using electromagnetic sensors, Philips opted for optical detection because that made it possible to put all of the electronics into the reusable instrument and keep the cost of the disposable cartridge to a minimum.
The key to the sensor is frustrated total internal reflection — a technique that’s been proposed as a way of building multitouch displays similar to those used on the iPhone but using light instead of body capacitance. The technique works by shining a light at a shallow angle onto the surface of glass or clear plastic. If the angle is shallow enough, then practically all of the light is reflected back — hardly any passes through the surface even though it’s transparent.
The ‘frustrated’ part comes in when you have an object on the other side of the surface. A quantum mechanical effect comes into play that interferes with the reflection because an evanescent field created by the light waves extends a short distance past the surface. An object in that field scatters some of the light so that some of it is not reflected directly.
This is the key to the touchscreen technology based on TFIR at New York University. A finger close to the surface scatters light so that detectors underneath pick it up. The Philips system measures how much the reflected light is affected by beads close to the surface.
“If a bead is present you get a lower reflected signal back. You don’t have to flow the beads away, just move them out of the evanescent field,” said Klunder. “It’s a very sensitive measure because you can detect almost individual particles.”
The optical detection technique puts a limit on the size of the protein that can be detected using the system — too long and you don’t get the interference effect. Short molecules also have problems, as it’s tough to get two antibodies to bind to them. This turned out to be a problem with measuring narcotics — those molecules are not big. So, Philips has chosen to focus on protein detection.
“This is a very nice technology and being commercialised now,” said Klunder. “We are collaborating with a French company, Biomémerieux, who are specialists in the field, because we are not experts in biochemistry.”
A further issue has been to increase the shelf life of the reagents stored in the cartridge. “The shelf life of antibody particles is typically a few months and there are no wet reagents onboard. If you don’t optimise this, the shelf life is a lot less than a month. And the temperature needs to be low,” said Klunder. “This is where you need industrial researchers. It is not something you can do in academia.”