European consortium turns to GaN devices for medical sensor arrays

Hospitals and medical laboratories have to analyze thousands of tiny samples every day. This is ideally carried out quickly, efficiently and with a high degree of sensitivity, enabling early detection of conditions such as AIDS, Creutzfeldt-Jakob Disease and cancer. Rapid diagnosis can save lives, improve a patient s quality of life and reduce medical treatment costs.

At the Technical University of Ilmenau, Germany, we are coordinating a three-year €3.7 million ($4.6 million) project, involving eight other European partners to construct the first instrument based on GaN devices to address this need. GaN and its related alloys are well suited to this task because unlike the GaAs and InP families they can form the basic chemical sensors without suffering from degradation caused by direct contact with acidic and alkaline solutions.

The GaN sensors, which are the key part of our "GaNano" instrument, analyze the chemical properties of nanolitre and picolitre samples that are brought into contact with the device s surface. The devices – essentially transistors with an eliminated top gate or a modified active gate region – can detect dipoles, polar liquids, changes in ion concentration and cell activity because this alters the device s surface potential and leads to a change in the current flowing through the underlying two-dimensional electron gas (2DEG).

The sensors can be tailored to respond to a certain type of substance by applying specific membranes to the gate area that are made from either biological cells or artificial materials. For example, researchers from the University of Crete and the Foundation of Research and Technology Hellas have modified our detectors to be sensitive to potassium by covering the gate area with a polyvinyl chloride membrane, which is doped with valinomycin, a large molecule made from amino acids.

Applying different types of organic membrane has enabled production of sensors that are selective to other cations like ammonium and sodium, and also to anions like nitrate and chloride. In each case the sensor s signal results from the potential difference at the interface between the membrane and the aqueous solution. This is created by the reaction between the ion carrier and the analyte ion. At the Technical University of Munich experiments have also shown that immobilized enzymes like penicillinase can be applied to the sensor s surface, altering the device s selectivity and sensitivity.

Our work with cations, anions and enzymes illustrates the potential of GaN-based sensors. Sensing with these devices can be extended to different biological systems by adapting the surface and the sensor, enabling a series of different detectors to be made that can form the basis for a multifunctional sensor array.

We apply our samples to the sensor s surface with a dispenser that resembles an inkjet printer head (see figure 1. Forcing a solution through a membrane and orifice creates a liquid jet that can be controlled to deliver samples at rates of up to 300 drops/s onto a moving sensor array. One or more droplets are applied to each sensor and by adjusting this system droplets can be delivered at 1–3 m/s and volumes of between 50 pl and 1 nl.

Our project also benefits from GaN s optical transparency at shorter wavelengths, where silicon, GaAs and InP are highly absorbing. This transparency enables biological samples to be identified by their fluorescence spectra, which often contain prominent features at ultraviolet wavelengths.

Members of the research team at Madrid Polytechnique University, TopGaN and Unipress have developed various GaN-based devices for this type of measurement, such as lasers and photodetectors. For determining the concentration of lipase – a key enzyme in the human body that is required for the absorption and digestion of nutrients in the intestines – we have built laser diodes emitting at 412 and 419 nm, and photodetectors with an InGaN-based filter that restricts detection to the 400–415 nm band, while negating the need for an external dielectric filter. These devices could be used to see if a patient is suffering from an inflamed pancreas by testing for a high concentration of pancreatic lipase.

All of our GaN devices have been installed in a temperature-and-humidity-controlled glove-box that reduces the evaporation rate of our various samples. The fast evaporation rate is a consequence of our "open" design, which has the advantage of fast mixing between solutions. The more common "closed" systems that route liquids through micron-sized channels do not suffer from fast evaporation rates, but mixing between solutions is slow.

The first continuous optical and electrical and measurements with the GaNano system were conducted on lipase at the Technical University of Ilmenau. This enzyme provides the catalyst for the decomposition of organic molecules (either 4-nitrophenylcaprilate or 4-nitrophenylacetate) into and an acid and a dye (4-nitrophenol). Our electrical measurements, which employed AlGaN/GaN sensors that did not require any modification to provide a selective response, monitored the change in pH of the products of this reaction.

After adding lipase the system s pH initially increases from 7.2 and then decreases, as expected, to 6.4 (see figure 2). The metabolic rate of the enzyme can be calculated from the pH value and a titration of the resulting acid. The optical measurements determined the concentration of the other product of the reaction, the dye, by measuring the transmission characteristics of the solution (see figure 3).

Our electrical and optical measurements enabled us to track the behaviour of both of the products of this reaction and observe the influence of lipase. With Analytik Jena and the European Aeronautic Defense and Space Company, our next step is to integrate these components to produce an instrument capable of simultaneously monitoring both products created in this reaction. Integrating these components demands a high degree of precision because droplets with volumes of just 50 pl have typical diameters of 60 μm. We are now tackling this challenge and when this is complete we will begin to make measurements on other biological materials. This will ultimately lead to the construction of a GaN tool for rapid identification of various diseases.

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www.ganano.eu.org.