A small and sensitive SPR instrument for chemotherapy monitoring

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Sensitive tools for rapid and reliable quantification of chemotherapy agents may improve treatment of leukemia and bone marrow transplant in adults undergoing chemotherapy. In particular, methotrexate (MTX) is a widely employed cytotoxic agent that offers major therapeutic benefits despite severe side effects. There is a clinical need for regular monitoring of the concentration of MTX during the course of a chemotherapy treatment, to adjust the dose for each patient and thus maximize efficacy while minimizing side effects. Frequent monitoring insures optimal dosage for patient's safety and treatment efficacy. Surface plasmon resonance (SPR) is commonly used as an optical technique for studying molecular recognition, and could serve to quantify drugs. However, current commercial SPR instruments are bulky, expensive and lack sensitivity in biological media, precluding their application in clinical settings; furthermore, instrument design restricts analysis to a laboratory. The latest breakthroughs in materials science and plasmonic instrument design exploit microhole arrays to enhance SPR response, and peptide surface chemistry to overcome the surface-fouling limitations, which typically plague commercial SPR instrumentation in presence of crude biofluids. We have applied these novel concepts of SPR technology to monitor the concentration of various molecules. We propose to integrate this label-free, fast, reliable, sensitive and effective technology to monitor MTX levels in the serum of chemotherapy patients. To achieve this objective, the SPR device will be prototyped as a functional platform that will be validated with actual serum samples from patients undergoing chemotherapy, in collaboration with a clinician biochemist, specialist of MTX dosing in hospital environment. The concentration of MTX obtained by SPR sensing in patients' sera will be compared to standard techniques, such as fluorescence polarization immunoassay (FPIA) and LC-MS/MS, to validate the SPR sensing technology. This application of the novel SPR device is thus designed to rapidly enhance patient care by providing clinicians a faster, sensitive and portable tool to perform the analysis of MTX during ongoing chemotherapy treatments.