An Ultra-Sensitive Biosensor Based on Mid-Infrared Diamond Waveguide Spectroscopy

In this presentation, our latest work in the development and the use of an ultra-sensitive biosensor based on diamond waveguides will be highlighted. We have during the last years been working on the design and fabrication of mid-infrared (MIR) diamond waveguides. The diamond MIR waveguides together with a broadband tunable quantum cascade laser (QCL), emitting in the so called molecular fingerprint region, are the two key elements in our newly developed label free MIR biosensor. In our approach MIR light is coupled into microfabricated diamond waveguide structures, which are purposefully designed to sustain single or multimode standing waves. The associated evanescent waves that are created at the waveguide surface will extend into the surrounding media and interact with the analyte thus provide the sensing volume. In existing commercial technologies, attenuated total reflection IR (ATR-IR) spectroscopy, IR light from a thermal emitter is coupled through a millimeter sized diamond crystal, with up to 10 internal reflections in the diamond crystal. This is a powerful technology and is today used for i.e. quality control in medical and food industry, protein analysis, forensics, etc. However, the relatively low sensitivity of this technique hinders its use in many applications. Our biosensor achieves unsurpassed sensitivity due to the large number of standing waves nodes created in our waveguides which roughly can be translated to the number of internal reflections per length unit is maximized. Moreover, the use of a bright QCL laser as a light source further increases the sensitivity of our biosensor – therefore an ultra-sensitive sensor is realized. Finally, the diamond waveguide material facilitates further functionalization by means of organic chemistry thus extending the capabilities of traditional silicon or gold based biosensor technologies, and we demonstrate here one possible route to fabricate selective affinity layers for protein fishing from complex mixtures.<br/>Several designs of diamond waveguides are discussed, ranging from thin film diamond slab waveguides, rib waveguides, to microfabricated free hanging diamond waveguides. We have recently showed how AlN can be used as cladding layer to overcome earlier difficulties in guiding light at longer wavelengths (5-10 µm). We will also present how we significantly can increase the sensitivity of the diamond waveguide sensor by depositing a high index film on the diamond waveguide. Using silicon as the high index film also opens up for easy functionalization of the sensor.<br/>The diamond waveguide sensor has been tested on different analytes, such as acetone and isopropanol, showing a very stable performance and very high sensitivity. We have therefore starting to work on “real-world” chemical sensing applications. Currently, we are analyzing different forms of the protein alpha-synuclein, which is relevant in understanding the mechanism behind Parkinson’s disease. We have previously shown that ATR-IR spectroscopy can be used to analyze the secondary structure of different alpha-synuclein aggregates. Moreover, it is also possible to see the difference in the IR-spectra between the native state and the neurotoxic misfolded state of the protein. However, the ATR element is impractical to functionalize and the sensitivity of the ATR-IR spectroscopy is too low to be used on relevant samples from patients. In contrast, our diamond waveguide biosensor exhibits the desired key properties to analyze the secondary structure of alpha-synuclein at biologically relevant concentrations. Future work includes the functionalization of the diamond waveguide sensor surface to selectively adsorb alpha-synuclein from cerebrospinal fluid, with the ultimate goal to detect Parkinson’s disease at an early stage.