A Surface-Plasmon Enhanced Mid-Infrared Lab-on-a-Chip for Real-Time Reaction Monitoring of Liquids

The mid-infrared (mid-IR) spectral range is highly suitable for selective and sensitive probing of molecules by addressing their fundamental fingerprint absorptions. While high performance gas sensing has already been demonstrated in many different experiments including frequency-comb based techniques and exploiting concepts from direct absorption spectroscopy to photo-acoustics and dispersion spectroscopy, the mid-IR analysis of liquids is still in its infancy. Though recently gaining particular interest, it is still in main parts limited to bulky detection systems like Fourier-Transform Interferometer (FTIR-)based sensors, demanding for liquid films on the order of a few micrometers only. This often results in time-consuming offline analytics, preventing real-time analysis of rapidly changing liquid systems like when undergoing chemical reactions or conformational changes of molecules in the sample.<br/>For enabling the next generation of liquid sensing by going beyond such limitations, we present in this work a novel high-performance monolithic mid-IR sensor. It relies on pioneering quantum cascade (QC) technology by merging a similar wavelength QC laser (QCL) and QC detector (QCD) into one active region and combining it with a novel mid-IR plasmonic concept. Using a surface-sensitive dielectric-loaded surface plasmon polariton (DLSPP) structure, which consists of a SiN-slab on a gold layer, results in a fingertip-sized optical sensor, highly suitable for the monitoring of liquids. In contrast to state-of-the-art systems, its robustness and compactness allow the real-time analysis of dynamical processes in liquids including inline and in-situ measurements by direct exposure to the liquid. In our DLSPP approach, the plasmonic mode propagates along the sample surface, being efficiently guided by more than 95% in the surrounding medium. Our presented FEM-based simulations confirm the preservation of the plasmonic capabilities also in a liquid matrix.<br/>We demonstrate the breakthrough performance of the plasmonic concept implemented into the sensor in an analytical chemistry experiment. We measure the time-dependent conformational changes of the model-protein bovine serum albumin (BSA) with our compact on-chip sensor. Time-resolved measurements are performed by combination of the device with a custom-made 60-μl flow cell for inline measurements at λ = 1620 cm⁻¹. We use a D₂O matrix for reduced background absorption, while maintaining comparable protein unfolding results as in biophysical buffer, i.e. H₂O. BSA unfolds irreversibly from α-helix to antiparallel β-sheets when heated from 20°C to 90°C. In our experiments we obtain the typical protein denaturation curves, following a sigmoidal Boltzmann equation (”s-shaped”) with increasing temperature. In good agreement with literature, we observe a decreasing transition temperature with increasing BSA-concentration, confirming the proper operation of our compact sensor. By additionally directly submerging the sensor into a beaker with the protein-analyte and monitoring its absorbance vs concentration curve (calibration line) for increasing BSA concentrations, we can extract the important figures-of-merit of our on-chip device. A comparison with a state-of-the-art attenuated total reflection (ATR-)FTIR reference system reveals the superior performance of our ultra-compact sensor with: 55-times higher absorbance, 120 times lower LOD (LOD_QCLD ∼75 ppm) and coverage of more than three order of concentrations of 0.0075 % to 9.23 %.<br/>In the second part of this paper, we will show how the plasmonic surface of our sensor can be further enhanced through functionalization. By depositing compatible mesoporous membranes based on ZrO₂ or TiO₂, molecules can be trapped close to the sample surface. This yields a significant increase in sensitivity by molecule enrichment factors well above 100 (e.g. 162 in a typical setting using a ZrO₂ membrane).