Development of a surface enhanced Raman scattering (SERS) sensor for point of care therapeutic drug monitoring in canine epilepsy

Epilepsy is the most prevalent neurological condition in canines, affecting 1.5-2% of dogs. In most cases, canine epilepsy is idiopathic and the condition is still poorly understood. Since epilepsy is incurable, treatment is intended to control the symptoms by reducing frequency and intensity of seizures, while minimizing side effects.

Therapeutic drug monitoring is therefore required to ensure the correct quantity of drug is administered and to confirm the efficacy of the drugs with minimal adverse effects. Phenobarbitone is the most commonly prescribed medication for canine epilepsy. Generally, the drug would be monitored by taking blood tests at the beginning of treatment and on occurrence of seizures; however, a quicker and less invasive test could provide a significant step in the understanding of idiopathic epilepsy and in monitoring drug treatment.

An ideal route to achieving this would be the development of a point-of-care (POC) sensor that could detect the drug in saliva, allowing regular non-invasive monitoring that could potentially be correlated with circulating levels of the drug in routine blood tests. The POC test would allow closer monitoring of drug levels and the correlation with onset of seizures, while minimizing patient distress.

Surface enhanced Raman scattering (SERS) is an ultrasensitive and highly specific technique that can be used for the label-free quantification of analytes. Since SERS gives molecularly specific vibrational information, analytes can be specifically identified and the unique SERS spectra obtained from individual molecules enables the detection and quantification of multiple targets simultaneously.

These attributes make SERS an attractive technique for POC analysis and its use has been demonstrated in various applications from drug analysis to medical diagnosis and in food safety.

The basis of SERS is that an enhancing substrate, usually in the form of metallic nanomaterials, will significantly increase the intrinsic Raman signal of a target analyte, greatly improving the sensitivity. By depositing metal nanomaterials in an array format, SERS enhancement can be tuned while also introducing a means of attracting molecules of interest to the specific areas where the enhancing substrate is deposited.

Self-assembled monolayers (SAMs) can be formed with various chemical moieties that will attract molecules to the surface based on chemical properties. This is particularly useful for the analysis of biological samples, as it allows the spectrum of the analyte to be separated from that of the biological medium. Additionally, this method of analyte binding removes the need for targeting molecules, labelling and wash steps, which is clearly advantageous in POC analysis.

SERS has previously been demonstrated for the detection of anti-epileptic drugs in human saliva, and in a POC format for monitoring the intravenous delivery of drugs. However, a POC test for measuring drug concentration in saliva is yet to be developed and this would be a life-changing step in monitoring canine epilepsy.