Increase in the adoption of liquid handling devices (LHD) can facilitate experimental activities. Initially adopted by businesses and industry-based laboratories, the practice has also moved to academic environments, where a wide range of non-standard/non-typical experiments can be performed. Current protocols or laboratory analyses require researchers to transfer liquids for the purpose of dilution, mixing, or inoculation, among other operations. LHD can render laboratories more efficient by performing more experiments per unit of time, by making operations robust and resilient against external factors and unforeseen events such as the COVID-19 pandemic, and by remote operation. The present work reviews literature that reported the adoption and utilisation of LHD available in the market and presents examples of their practical use. Applications demonstrate the critical role of automation in research development and its ability to reduce human intervention in the experimental workflow. Ultimately, this work will provide guidance to academic researchers to determine which LHD can fulfil their needs and how to exploit their use in both conventional and non-conventional applications. Furthermore, the breadth of applications and the scarcity of academic institutions involved in research and development that utilise these devices highlights an important area of opportunity for shift in technology to maximize research outcomes.

/pdf/automated-liquid-handling-operations-for-robust-resilient-1oi5u3x4.pdf

Automated liquid-handling operations for robust, resilient, and efficient bio-based laboratory practices

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9810479

A fast, efficient, and scalable method for purifying recombinant SARS-CoV-2 spike protein

The spike (S) glycoprotein of the pandemic virus, SARS-CoV-2, is a critically important target of vaccine design and therapeutic development. A high-yield, scalable, cGMP-compliant downstream process for the stabilized, soluble, native-like S protein ectodomain is necessary to meet the extensive material requirements for ongoing research and development. As of June 2021, S proteins have exclusively been purified using difficult-to-scale, low-yield methodologies such as affinity and size-exclusion chromatography. Herein we present the first known non-affinity purification method for two S constructs, S_dF_2P and HexaPro, expressed in the mammalian cell line, CHO-DG44. A high-throughput resin screen on the Tecan Freedom EVO200 automated bioprocess workstation led to identification of ion exchange resins as viable purification steps. The chromatographic unit operations along with industry-standard methodologies for viral clearances, low pH treatment and 20 nm filtration, were assessed for feasibility. The developed process was applied to purify HexaPro from a CHO-DG44 stable pool harvest and yielded the highest yet reported amount of pure S protein. Our results demonstrate that commercially available chromatography resins are suitable for cGMP manufacturing of SARS-CoV-2 Spike protein constructs. We anticipate our results will provide a blueprint for worldwide biopharmaceutical production laboratories, as well as a starting point for process intensification. 

/pdf/advances-in-purification-of-sars-cov-2-spike-ectodomain-9cly2leq.pdf

Kristin M. Leach

Papers

Advances in purification of SARS-CoV-2 spike ectodomain protein using high-throughput screening and non-affinity methods