SLAS 2020 European Sample Management Symposium

The discovery and production of biologic therapeutics is an ever-expanding frontier in the biotech/pharmaceutical sector. As a result, the need has arisen to develop efficient and robust means of managing biomolecules such as nucleic acids and proteins, and to address some of the unique challenges they present to the sample management community. These two categories of reagents are particularly relevant because nucleic acids are foundational for the production of suitable protein/antibody drug candidates and the protein reagents needed to support the drug discovery pipeline. When managed across individual labs, potential can exist for these important research samples to be unavailable for use in the broader organization or to be discarded due to unknown or compromised sample identity, integrity and/or location.

This talk will highlight workflow optimization strategies, including automation and bioinformatics, employed in Genentech’s BioMolecular Resources Sample Management facility that enable us to empower research by providing an efficient means to receive, store, produce, track and distribute these materials. We will focus on our ongoing efforts to develop new high-throughput automated processes for sample pooling to support large and small scale protein expression workflows and other research applications. We will also share our future vision for a state-of-the-art nucleic acid and protein sample management facility and the current challenges associated with implementation of this vision.

Historically, laboratory automation was used mostly to scale up repetitive tasks. Recent developments make it possible to expand the scope of automation and digital laboratory solutions to encompass more complex processes, peripheral work and experimental design and execution. Here, we consider how device, augmented and digital innovations could impact the way we work.

Innovative design and deployment of novel labware, instrumentation and software technologies have delivered an automated, fully acoustic platform and a step-change in small molecule Sample Management (SM) processes.

For many years, conventional SM workflows have included multiple sample transfers between vessels, using a hybrid of contact and non-contact dispensing, which are cumulatively wasteful. These combine to affect excessive sample consumption, necessitating chemists to synthesise superfluous quantities of compound.

Here we show high quality concordant datasets from the first fully acoustic workflow for physico-chemical, enzymatic, cellular and in vitro ADME assays. We also show a reduction in (i) sample usage in these assays, (ii) DMSO usage throughout the process, and (iii) future synthesis requirements.

An acoustically compatible storage tube (FluidX™ AcoustiX™ Sample Tubes, Brooks Life Sciences, UK) was designed with optimum geometry for dispensing accuracy and speed, whilst maintaining a working sample volume able to sustain a 10-year screening lifetime. Co-moulded capping technology for these tubes has resulted in increased durability for multiple dispense access and sample longevity, whilst a novel split barcode at the base affords a central opening for transmission of the acoustic pulse.

A tube-compatible acoustic liquid handler (Echo® 655T Liquid Handler, Beckman Coulter Life Sciences, USA) has been designed to utilise acoustically compatible storage tubes including a faster drop-transfer rate via a new transducer-focussing mechanism. A new dryer system removes moisture on the exterior of the tube, alongside local humidity control in the drop-transfer zone to maintain sample integrity.

 The development of a new, fully acoustic workflow has minimised sample handling and waste, enabling miniaturisation of assays and hence reducing the amounts of sample required for synthesis to support drug discovery projects. We have implemented and validated novel labware and instruments for a transformative and sustainable solution to many drug discovery issues applicable across the industry.

Increasing success rates and decreasing cycle times are key objectives in the pharmaceutical industry. As such, screening platforms deployed to identify starting points for chemistry are constantly evolving to meet this challenge. Traditionally, Ultra High Throughput Screening of millions of compounds in 1536 well plates, and the sample management infrastructure which accompanies that, have been the cornerstone of hit identification in pharma, and have been used to successfully identify quality starting points for numerous projects. In the past decade, other technologies such as DNA Encoded Library Screening and Affinity Selection Mass Spectrometry have emerged, which reduce the requirement for extensive assay development and enable rapid identification of binders to the target of interest, often for multiple targets in parallel. Additionally, there has been an increase in the use of human disease relevant cell systems in early discovery with the aim of identifying molecules with improved clinical translation. However, the costs, the complexity of biology, and especially the limited scalability of cells, limit how these can be used at a scale compatible with high-throughput plate-based HTS formats.         Here we will discuss how the screening platforms described above are being deployed at GSK, and the interplay between those screening platforms and the sample management infrastructure that they critically depend on. We will discuss the challenges, and opportunities for sample management in the context of this evolving screening landscape.

The CompuGene robotics platform was designed to automate DNA assembly and characterization of microbial cell factories. These capabilities will be presented in the framework of research currently being conducted by the kabisch-lab. These examples include managing of robotic protocols using git, a simple active-learning approach to characterize molecular switches, an open-source colony picking solution and the optimization of growth parameters for various applications.