MESA+ University of Twente
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Aurel Ymeti

Development of a Multichannel Integrated Young Interferometer Immunosensor

What was your thesis about?

The work we did is based on the development of a highly sensitive multichannel integrated interferometric sensor for measurement of very low concentrations of certain substances in a given sample solution; traces of pesticides in water or virus particles in blood for example. We have shown that this sensor is extremely sensitive and the detection of one single virus particle is feasible.

In short, laser light is coupled into an integrated optical channel waveguide and split by a Y-junction to two output parallel branches positioned at a certain distance from each other. An interference pattern is generated as a result of the overlap of both outgoing divergent beams. The interference pattern is recorded by a CCD camera, which is placed at a given distance from the endface of the integrated chip. A sensing window is realized on the top of the measuring channel where the sampling liquids to be analyzed are applied. When a binding event takes place on the sensing window of the measuring channel, a phase change between reference and measuring branches will result and the interference pattern will be shifted with respect to the camera surface. By measuring the spatial shift of the interference pattern, the phase change can be calculated, and furthermore, the refractive index change occurring on the sensing window of the measuring arm can be determined.

This tells you something about the quantity (one, two, or a thousand analyte molecules), but it does not tell you anything about the properties of the substance. For that we coat the surface of the sensing window with antibodies only binding to a particular type of analyte.

So first you have to determine what kind of substance you are dealing with?

Yes, and based on that, we measure the quantity. We have implemented different channels to have several measuring windows. Applying different antibody layers to different channels, we can detect different analytes at the same time. In our preliminary device, we can detect three analytes simultaneously, but with the set-up parameters we have, we should be able to detect up to 15.

Is this type of device completely new?

Interferometers have been developed before, but we upgraded a two-channel device to a multichannel one and we improved the sensitivity enormously by using silicon technology, which is well developed in the MESA+ Institute for Nanotechnology.

The multichannel device was also successfully used as a first interferometric sensor for detection of virus particles in several minutes, being relevant for fast screening purposes. Moreover, our sensor is one of the first interferometric devices where microfluidics is applied, resulting in fast measurements and improving further performance of this type of sensor.

We had very close collaboration with the Lightwave Devices Group (LDG), Lionix BV (a MESA+ company specialized in integrated optics and microfluidics) and Paradox BV that contributed to the chemical side of the project.

An application for a Dutch patent is made in February and we may go for a European one after that.

Filing patents is expensive I am told, so who pays?

In this case STW. However, STW has an agreement with the company that commercializes it, and of course, it is the idea that they will get their return on investment and our group (Biophysical Engineering) may also benefit from the patent application.

Who organizes this close collaboration?

One of my promoters, prof.dr. Jan Greve, advised on the frequent consultation with LDG, because he knew that they had experience with integrated optics. From the chemical point of view, STW invited several companies wanting to use these devices for different applications, e.g. measuring of viruses. Every six months we had a users’ committee meeting, discussing our progress and exchanging ideas.

Will this device be deployed in hospital laboratories?

That is the main idea. Paradocsens BV will commercialize it, especially the multichannel application for detection of viruses such as SARS in a few seconds only.

With a bit of luck, the first prototype will be finished in April this year.

With this SARS scare your investigation is of topical interest, isn’t it?

Yes, we are all rather excited about it. This sensor also offers the possibility for monitoring proteins that are associated with virus particles such as HIV, Hepatitis B, etc., offering another way for detection of viruses.

Would it also work in the early detection of cancer?

No investigation is made for detection of rare cancer cells yet. There are however other techniques that can perform this task. A subgroup of Biophysical Engineering where I work now as a postdoc (in close collaboration with Immunicon Europe) is doing just that: besides testing on HIV, we are dealing with the detection of rare cancer cells.

Now a completely different question, you are from Albania, how did you get here?

After receiving the MSc degree in physics at the University of Tirana, Faculty of Natural Sciences, in 1996, I was appointed as a teaching assistant in the Department of Physics at the Polytechnic University of Tirana. In 1997, I went to the University of Siegen in Germany to follow an international program doing research into high-energy physics. Then I found this project at the University of Twente in applied physics, which interested me a lot and I applied for it. The multichannel sensor described in this thesis is the result of the work I have been doing since 1999.

So there are no plans to go back to Albania?

Not in the immediate future. My wife joined me here in the University of Twente; she is also doing a PhD here on a very interesting project on artificial cells, which will detect and destroy a specific target cell, e.g. a cancer one, and it will not be recognized by the immunosystem.

So we are both working in medically orientated applied physics.

Isn’t this a bit of a brain drain from Albania?

Yes, it is. However, if you want to do interesting research, at this moment you do not have all necessary facilities there.

First, we had the idea to gain some experience in Western European countries or in the States and then go back. Now it looks like we are staying a bit longer. Nevertheless, the option is still open that we will go back at a certain moment.