Mid-infrared germanium-on-silicon waveguide sensor for therapeutic drug monitoring of phenytoin

TL;DR

This paper presents a germanium-on-silicon waveguide sensor operating in the mid-infrared for rapid, accurate, and miniaturized therapeutic drug monitoring of phenytoin, capable of detecting sub-therapeutic levels and quantifying within the therapeutic range.

Contribution

It introduces a novel mid-infrared waveguide sensor integrated on silicon for point-of-care drug monitoring, demonstrating high sensitivity and quantification capability for phenytoin in serum.

Findings

Limit of detection of 2.20 mg/L for phenytoin.

Sensor maintains dose-dependent response up to 40 mg/L.

Potential for compact, scalable point-of-care drug testing platforms.

Abstract

We report the design, fabrication and characterization of evanescent mid-infrared germanium-on-silicon waveguide sensors for therapeutic drug monitoring (TDM). TDM requires rapid and accurate quantification of serum drug levels but existing clinical assays rely on laboratory-based instrumentation that limits point-of-care deployment. In this work, tunable diode laser absorption spectroscopy was used to analyze dried samples of the anti-seizure medication phenytoin in the spectral region of $\lambda$ = 5.6 - 6.0 $\mu$m. A limit of detection of 2.20 mg/L was achieved for extracted samples, where phenytoin was first added to human serum and subsequently isolated using liquid-liquid extraction. This limit is significantly below the therapeutic window of 10 - 20 mg/L for phenytoin, enabling detection of sub-therapeutic concentrations. At the same time, the sensor maintains a consistent dose-dependent response up to 40 mg/L, demonstrating its capability to quantify concentrations across the therapeutic window and above the upper therapeutic limit. This validates the use of silicon photonics for biomedical infrared spectroscopy for patients undergoing drug therapy, whether the serum-drug concentration is either too high or too low. These results highlight the potential of mid-IR integrated photonics to form the basis of compact, scalable platforms for point-of-care TDM.