A microfluidic toolkit for drug delivery particle discovery

自动化和高通量筛选被用于制药行业，以制造和测试治疗开发过程中的大量化合物。选择药物是为了覆盖大范围的化学多样性，以广泛地探索生物功能，而不需要更早的假设。尽管这在活性药物成分(API)的发现上取得了巨大的成功，但这些概念目前还没有被用于开发软物质药物输送载体(脂质体、LNPs等)本身。由于缺乏制造这种结构的文库的技术，在递送粒子本身的结构方面有巨大的创新空间。在这个项目中，我们将开发微流控平台来创建不同的脂类NP配方、形态、电荷、大小、两亲性组成和封装的遗传物质类型的海量文库。在此基础上，我们将开发集成的芯片实验室平台，以测试它们通过体外测试将遗传物质输送到细胞的能力。通过这样做，我们的目标是为高通量制造和筛选软纳米粒子库的新前沿建立基础设施。我们利用这一点作为高通量筛选平台的基础，在那里我们将筛选纳米颗粒本身(与活性成分相反)。这提供了现有方法的概念转变，这些方法依赖于粒子类型的逐个合理设计和制造。与我们的工业合作伙伴(阿斯利康)一起，我们将把我们的技术应用于制药部门的科学优先事项。一旦建立，我们的平台可以应用于需要软物质粒子发现的*任何*应用，包括药物/疫苗治疗应用和生物传感。

Automation and high throughput screens are used in the pharma industry to manufacture and test massive numbers of compounds in the therapeutic development process. Drugs are chosen to cover large areas of chemical diversity to broadly probe biological function without earlier assumptions. Although this has proven hugely successful in the discovery of active pharmaceutical ingredients (APIs), such concepts are currently not used to develop soft matter drug delivery vehicles (liposomes, LNPs etc) themselves. There is huge scope for innovation in terms of the architectures of the delivery particle themselves, driven by the lack of technologies to manufacture libraries of such structures.In this project we will develop microfluidic platforms to create massive libraries of different lipid NP formulations, morphology, charge, sizes, amphiphile composition, and encapsulated genetic material type. Building on this, we will develop integrated lab-on-chip platforms to test their ability to deliver genetic material to cells via in vitro assays. In doing so, we aim to establish the infrastructure for a new frontier in high-throughput manufacture and screening of soft nanoparticle libraries. We use this as a basis for a high-throughput screening platform, where we will screen the nanoparticle itself (as opposed to the active ingredient). This offers a conceptual shift from existing approaches that rely on one-by-one rational design and manufacture of particle types. Together with our industrial collaborators (AstraZeneca) we will apply our technology to scientific priorities of the pharmaceutical sector. Once established, our platforms can be applied to *any* application where soft matter particle discovery is needed, including in drug/vaccine therapeutic delivery applications and in biosensing.