Integrated Photonics and Applications Centre, School of Engineering, RMIT University, Melbourne, VIC, Australia.
Nanobiosensors and Bioanalytical Applications Group, Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, BIST and CIBER-BBN, Campus UAB, Ed-ICN2, Barcelona, Spain.
Methods Mol Biol. 2022;2393:89-125. doi: 10.1007/978-1-0716-1803-5_6.
The bimodal waveguide (BiMW) biosensor is an innovative common path interferometric sensor based on the evanescent field detection principle. This biosensor allows for the direct detection of virtually any biomolecular interaction in a label-free scheme by using specific biorecognition elements. Due to its inherent ultrasensitivity, it has been employed for the monitoring of relevant nucleic-acid sequences such as mRNA transcripts or microRNAs present at the attomolar-femtomolar concentration level in human samples. The application of the BiMW biosensor to detect these nucleic acids can be a powerful analytical tool for diagnosis and prognosis of complex illnesses, such as cancer, where these biomarkers play a major role. The BiMW sensor is fabricated using standard silicon-based microelectronics technology, which allows its miniaturization and cost-effective production, meeting the requirements of portability and disposability for the development of point-of-care (PoC) sensing platforms.In this chapter, we describe the working principle of the BiMW biosensor as well as its application for the analysis of nucleic acids. Concretely, we show a detailed description of DNA functionalization procedures and the complete analysis of two different RNA biomarkers for cancer diagnosis: (1) the analysis of mRNA transcripts generated by alternative splicing of Fas gene, and (2) the detection of miRNA 181a from urine liquid biopsies, for the early diagnosis of bladder cancer. The biosensing detection is performed by a direct assay in real time, by monitoring the changes in the intensity pattern of the light propagating through the BiMW biosensor, due to the hybridization of the target with the specific DNA probe previously functionalized on the BiMW sensor surface.
双模波导（BiMW）生物传感器是一种基于消逝场检测原理的创新型共光路干涉传感器。这种生物传感器允许在无标记方案中直接检测几乎任何生物分子相互作用，使用特定的生物识别元件。由于其固有超高灵敏度，它已被用于监测相关核酸序列，如在人类样本中处于飞摩尔-皮摩尔浓度水平的 mRNA 转录物或 microRNAs。BiMW 生物传感器用于检测这些核酸的应用可以成为诊断和预测复杂疾病（如癌症）的强大分析工具，在这些疾病中，这些生物标志物起着主要作用。BiMW 传感器使用标准的硅基微电子技术制造，允许其小型化和具有成本效益的生产，满足便携式和一次性的要求，以开发即时护理（PoC）传感平台。在本章中，我们描述了 BiMW 生物传感器的工作原理及其在核酸分析中的应用。具体来说，我们展示了 DNA 功能化程序的详细描述以及两种不同的癌症诊断 RNA 生物标志物的完整分析：（1）通过 Fas 基因的选择性剪接生成的 mRNA 转录物的分析，以及（2）来自尿液液体活检的 miRNA 181a 的检测，用于膀胱癌的早期诊断。生物传感检测是通过直接实时分析进行的，通过监测通过 BiMW 生物传感器传播的光的强度图案的变化来进行，这是由于目标与先前在 BiMW 传感器表面功能化的特定 DNA 探针的杂交引起的。
