A small and sensitive SPR instrument for chemotherapy monitoring

快速、可靠地量化化疗药物的灵敏工具可能会改善正在接受化疗的成年人的白血病和骨髓移植的治疗。特别是，甲氨蝶呤(MTX)是一种广泛使用的细胞毒剂，尽管有严重的副作用，但仍具有主要的治疗效果。临床上需要在化疗过程中定期监测MTX的浓度，以调整每个患者的剂量，从而在最大限度地提高疗效的同时将副作用降至最低。频繁的监测确保了患者的安全和治疗效果的最佳剂量。表面等离子体共振(SPR)是研究分子识别的一种常用的光学技术，可用于药物的定量。然而，目前商业化的SPR仪器体积庞大、价格昂贵，在生物介质中缺乏灵敏度，阻碍了它们在临床环境中的应用；此外，仪器设计限制了分析只能在实验室进行。材料科学和等离子体仪器设计的最新突破是利用微孔阵列来增强SPR响应，利用多肽表面化学来克服表面污染的限制，这些限制通常在存在原始生物流体的情况下困扰着商业SPR仪器。我们已经将这些SPR技术的新概念应用于监测各种分子的浓度。我们建议集成这一无标记、快速、可靠、灵敏和有效的技术来监测化疗患者血清中的MTX水平。为了实现这一目标，SPR设备将被原型化为一个功能平台，将与临床医生生物化学家、医院环境中MTX剂量的专家合作，通过来自接受化疗的患者的实际血清样本进行验证。通过SPR传感获得的患者血清中MTX的浓度将与标准技术，如荧光偏振免疫分析(FPIA)和LC-MS/MS进行比较，以验证SPR传感技术。因此，这种新型SPR设备的应用旨在通过为临床医生提供一种更快、更灵敏和便携的工具来分析正在进行的化疗期间的MTX，从而迅速加强患者的护理。

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.