Development of A Specialized Platform for Innovative Research Exploration (ASPIRE)

National Center For Advancing Translational Sciences

Investigators

Linked publications, trials & patents

Abstract

ASPIRE Integrated Computational Platform The ASPIRE Integrated Computational Platform (AICP) is being developed that will provide the chemical intelligence to support automated, high throughput synthesis. The AICP has a modular design, in the center of which is a Reaction Data Management Application Programming Interface (RDM API). This platform is critical to enable the extramural researchers who are part of the ASPIRE program. The Reaction Knowledgebase currently stores 100K public domain reaction data. We started a collaborative project to showcase how the AICP can transform probe development projects in the structure optimization phase. We intend to integrate NCATS ELN data into the internal Reaction Knowledgebase, upon the approval of NCATS stakeholder. Building on our blockchain technology we developed a prototype of a Reaction Portal (RP) which aims to be an experiment designer, data analysis and data sharing platform, enabling NCATS scientist and external collaborators to securely generate, store, analyze and exchange their data. A major component of this portal, the “Network Widget” has been developed. Besides allowing chemists to design and analyze synthesis routes, it was designed to be repurposed in another network analysis related research settings, i.e. in systems-biology related projects. Finalized installation of Reaction Screening platform Installation of an inhouse reaction screening platform consisting of a dual liquid- and solid-dispensing workstation provided by UnChained Laboratories and a large glovebox provided by MBraun for preparing, conducting, and processing high-throughput reaction screening experiments under completely inert conditions. Numerous experiments are being conducted on the UnChained Labs platform in addition customizations that will facilitate analysis and applications of open source Bayesian optimization algorithms. The analytical processing platform purchased from Virscidian to be used to process reaction screening data has been expanded to support the QC operations of Compound Management. Chemical Inventory In preparation for seamless integration of reaction preparation for automated synthesis, the complete chemical inventory was downloaded, analyzed, curated, and annotated for the purposes of modeling of a next generation inventory management system for chemical synthesis. From this work a set of requirements have been drafted along with a functional specification to guide the development of a next generation chemical inventory system. Provisional Patent Applications on Innovative hardware and software The vision of the ASPIRE project is to provide a homogenous integration link between the regular laboratory and a fully integrated, nearly autonomous system. To accomplish this, smaller-scale projects that address gaps in the medicinal chemistry workflow have been implemented to redesign the tools that chemists use at the bench allowing translation to automatic setup and execution. Provisional patents have been submitted for: a) a novel workstation that conducts cartridge-based workup processes for chemical reactions; b) a device used for inerting the headspace of glass reactors during reaction amenable to both manual and automated use; c) a software application based on block chain technology to manage and protect intellectual property generated in the laboratory. In addition, a PCT application is being pursued for the development of a versatile batch evaporator for use at both at the bench or at scale in a fully automated implementation. Significant equipment and processes progress made. Core integrated benchtop chemistry capabilities include serial/batch processing for SPE/Chromatography, evaporation, integrated balance, reaction platforms, fed by in-house designed high density storage connected to in-house inventory software as well as compound management. Automated qNMR/NMR sample prep with Analytical chemistry using Sirius MultiTasker and OmniTasker. Automated purification module design complete. Indigo After years of work the Indigo Reactor is now fully installed at NCATS and is in an operational mode performing benchmark reactions. IOT - NCATS Laboratory Dashboard (Azure integration fully functional) A significant component of the ASPIRE project is to create a sustainable ecosystem of integrated technologies that realizes the goal of creating ‘Real-Time Translational Science’ by accessing and leveraging capabilities offered by modern cloud-computing technologies into more secure, effective, and scalable data sharing strategies and implementations. To this end, we have successfully integrated instrument access through the Azure clouding computing services and standardized the exchanges of consumables and data between workstations typically used in a chemistry laboratory setting. These changes will significantly improve the continuity of experiment execution by enabling remote connectivity to lab instrumentation while adding important experimental context to execution of research workflows. Initiation of Research Collaboration Agreements (RCA) with extramural organizations Five extramural collaborations/projects (RFAs) well underway since Fall 2022, with the 3 virtual collaborations ending this past May 2024. Physical Modules Lee Cronin, University of Glasgow: The Chemputer In this collaborative project we will develop a system for the automation and execution of chemical reactions across a range of hardware and scales for the synthesis of known and unknown molecules. Graham Cooks, Purdue University: High throughput infrastructure for reaction screening and bioassays Mass spectrometry (MS) is a powerful and widely applicable analytical method for qualitative and quantitative analysis of compounds of all types and sizes. Desorption electrospray ionization (DESI) is an ambient ionization method in which samples are analyzed in the open air by impact of primary droplets. Given the ability to position an array of samples relative to the mass spectrometer, DESI-MS becomes a high throughput (HT) chemical analysis method. Virtual Modules Conner Coley, MIT: Informatics and Machine Learning Modules for Reaching Planning, Scheduling, Simulation, and Optimization in the ASPIRE Autonomous Laboratory This collaborative project comprises the development of several virtual modules to support the multi-step chemical synthesis of new molecules in autonomous laboratories. Gaurav Chopra, Purdue University: Chemical instruments-aware distributed blockchain based open AI platform to accelerate drug discovery Artificial Intelligence (AI) and Automation has the potential to accelerate several stages of the drug discovery process, including the design-make-test-analyze optimization cycle, typically faced by medicinal chemists. However, several roadblocks exist resulting in too long timelines to deliver much needed innovation to patients with unmet needs. Barry Bunin, Collaborative Drug Discovery (CDD): Virtual Approaches to New Chemistries This project is being proposed as a modular component that will fit in with the large-scale automated synthesis program at NCATS and interoperate with other informatics tools such as retrosynthetic analysis and inventory management. Public Health Impact Statement ASPIRE promotes multidisciplinary collaborations among government, academic and pharmaceutical researchers; funders; professional societies; scientific publishers; and other stakeholders. ASPIRE supports NCATS’ work to develop, demonstrate and disseminate innovative technologies that will bring diagnosis and treatments to patients and will deliver on NIH’s efforts to increase reproducibility and scientific rigor. ASPIRE will realize the goal/dream of achieving Real Time Translational Science.