Developing an ultrawide dynamic range analytical platform for biomarker panel analysis in serum

开发用于血清中生物标志物组分析的超宽动态范围分析平台

• 批准号: 2597942
• 金额: --
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2597942
• 关键词: Developing; ultrawide; dynamic; range; analytical

The direct detection of biomarker species in biofluid samples via specific bioaffinity interactions is one of the most powerful tools for improving healthcare. However, for many diseases it is becoming increasingly clear that reliable diagnostics cannot be achieved by simply focusing on only one target species per measurement, despite the ongoing search for diagnostic simplicity and portability. Instead, a suite or panel of biomarkers needs to be accurately compared in order to provide an accurate disease snapshot. Particularly challenging is the robust and quantitative comparison of multiple biomolecular targets simultaneously at concentrations ranging from micromolar (~10-6 M) to below femtomolar (<10-15 M) in an environment as complex as blood serum. This project aims to address this measurement challenge utilising a combination of both optical instrumentation and data analysis design alongside the preparation and functionalisation of nanoparticles and integrated 3D-printed microfluidics for sample delivery and preparation. These will be applied to deliver a unique mutli-modal imaging instrument platform that enables rapid and high-throughput identification of both individual and nanoparticles assembled in the presence of a target molecule alongside the other species such as extracellular vesicles. The system performance will be demonstrated using biomarkers associated with two very challenging health conditions: (i) neurological disease, and (ii) pancreatic cancer, with a key objective being able to directly detect relative concentrations of multiple species in a patient serum sample within a relatively short timescale. Ultimately, being able to perform such measurements robustly also has the potential to be adapted to a large variety of other diseases as well as being a fundamental tool for nanoparticle design and characterisation, both of which further increase the potential impact and diversity of this project.

通过特定的生物亲和力相互作用直接检测生物流体样品中的生物标志物物种是改善医疗保健的最强大工具之一。但是，对于许多疾病而言，越来越清楚的是，尽管持续寻找诊断性的简单性和可移植性，但只能通过仅专注于一个目标物种来实现可靠的诊断。取而代之的是，需要准确比较一个套件或面板，以提供准确的疾病快照。特别具有挑战性的是，在像血清一样复杂的环境中，从微摩尔（〜10-6 m）到低于femtomall（<10-15 m）的多个生物分子靶标的稳健和定量比较。该项目的目的是利用光学仪器和数据分析设计的组合以及纳米颗粒的准备和功能化以及集成的3D打印微流体的组合，以应对这一测量挑战。这些将应用于提供独特的Mutli-Modal成像仪表平台，该平台可以在目标分子存在的情况下与其他物种（如细胞外囊泡）一起组装的个体和纳米颗粒的快速和高通量鉴定。将使用与两个非常具有挑战性的健康状况相关的生物标志物来证明系统性能：（i）神经系统疾病和（ii）胰腺癌，其关键目标能够在相对短的时间表中直接检测患者血清样品中多种物种的相对浓度。最终，能够鲁棒进行此类测量也有可能适应各种其他疾病，并且是纳米颗粒设计和表征的基本工具，这两者都进一步增加了该项目的潜在影响和多样性。