RII Track-4:NSF: Design of Bioresponsive Liquid Crystal Droplets for Sensing in Cellular Environments

生物分析物的检测在许多工业和医疗保健环境中是至关重要的。例如，大规模生产基于细胞的治疗产品的一个主要挑战是需要可扩展、快速和敏感的工具来监测微生物污染，以确保产品安全。该项目将为设计基于微尺度热致液晶(LCS)液滴的传感平台提供基础知识，用于检测细胞培养基中的微生物污染物。先前的研究表明，液滴液晶传感器在检测水溶液中的化学和生物分析物时具有显着的灵敏度。这种方法有几个优点，包括直接的检测方案(即，在接触分析物之前和之后观察LC液滴)，分析所需的样品体积小(微升)，以及使用基础研究仪器(例如，带有偏振光附件的光学显微镜)。因此，液滴为开发可快速展开的传感平台提供了一种很有前途的工具。所产生的知识可用于开发各种具有社会重要性的分析物的传感器，例如新出现的环境污染物。国家科学基金会EPSCoR RII Track-4研究人员项目将促进在为拉美裔服务的波多黎各大学(UPRM)对代表不足的少数族裔进行教育和培训，并通过长期访问威斯康星大学麦迪逊分校提供指导和跨学科研究机会，提高STEM中妇女的地位。该项目旨在开发基于微尺度热致液晶液滴的传感平台设计指南，用于快速、灵敏和选择性地检测蜂窝环境中的微生物污染物。液滴为灵敏地检测水环境中的各种分析物(即表面活性剂、脂类、蛋白质、细胞)提供了有用和通用的平台。该检测方案基于LC液滴在暴露于分析物时的光学外观的变化。使用偏振光显微镜可以很容易地实时观察到这些变化。然而，从实用的角度来看，这些材料的潜力仍然有限，因为液滴在胶体上并不稳定。为了应对这一挑战，该项目将开发设计基于液滴的传感器的方法，以提高保质期稳定性和增强检测灵敏度。使用表面化学性质可调的纳米颗粒(NPs)并吸附在LC界面上，可以得到在较长时间内(3个月)稳定的LC液滴。该项目还旨在开发NP修饰的液滴，用于设计生物响应材料，以检测细胞环境中的微生物污染物。将采用跨学科的方法来评估和量化NP修饰的液滴在暴露于不同组成的模型磷脂膜和活细胞(例如真菌、细菌、哺乳动物细胞)时的光学响应的变化。实验结果将建立NP表面化学和NP稳定的液滴对不同类型的脂膜和细胞的检测灵敏度之间的关系，并将为表面修饰的NPs赋予基于LC的传感系统选择性的潜力提供洞察力。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The detection of biological analytes is critical in many industrial and healthcare settings. For example, a major challenge in the large-scale production of cell-based therapeutic products is the need for scalable, rapid, and sensitive tools for monitoring microbial contamination to ensure product safety. This project will generate fundamental knowledge toward designing sensing platforms based on microscale droplets of thermotropic liquid crystals (LCs) for detecting microbial contaminants in cell culture media. Previous research has shown the remarkable sensitivity of droplet-based LC sensors when detecting chemical and biological analytes in aqueous solutions. This approach offers several advantages, including a straightforward detection scheme (i.e., observation of LC droplets before and after exposure to an analyte), small sample volume required for analysis (microliters), and the use of basic research instrumentation (e.g., optical microscopes with polarized light attachments). LC droplets thus provide a promising tool for developing rapidly deployable sensing platforms. The knowledge generated can be applied to the development of sensors for a wide range of analytes of societal importance, such as emerging environmental contaminants. The NSF EPSCoR RII Track-4 Research Fellows project will foster education and training of underrepresented minorities at the University of Puerto Rico-Mayagüez (UPRM), a Hispanic-Serving Institution, and the advancement of women in STEM through mentorship and cross-disciplinary research opportunities with extended visits to the University of Wisconsin-Madison. This project seeks to develop guidelines for designing sensing platforms based on microscale droplets of thermotropic LCs for the rapid, sensitive, and selective detection of microbial contaminants in cellular environments. LC droplets provide useful and versatile platforms for the sensitive detection of a wide range of analytes in aqueous environments (i.e., surfactants, lipids, proteins, cells). The detection scheme is based on changes in the optical appearance of LC droplets upon exposure to an analyte. These changes can be readily observed, in real-time, using polarized light microscopy. However, from a practical perspective, the potential of these materials remains limited because LC droplets are not colloidally stable. To address this challenge, the project will develop approaches for designing LC droplet-based sensors with improved shelf-life stability and enhanced detection sensitivity. Using nanoparticles (NPs) with tunable surface chemistries and that adsorb to the LC interface leads to LC droplets that are stable for extended periods ( 3 months). This project also aims to develop NP-decorated LC droplets for the design of bioresponsive materials to detect microbial contaminants in cellular environments. A cross-disciplinary approach will be implemented to evaluate and quantify the changes in the optical responses of NP-decorated LC droplets upon exposure to model phospholipid membranes of varying compositions and to live cells (e.g., fungi, bacteria, mammalian cells). The experimental results will establish relationships between NP surface chemistry and the detection sensitivity of NP-stabilized LC droplets toward different types of lipid membranes and cells and will provide insights into the potential of surface-modified NPs to impart selectivity to the LC-based sensing system.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.