Demand for automation in the analytical science field is increasing, largely driven by a surge of interest in biotherapeutics. In contrast to small molecule drugs, biotherapeutics are large, complex molecules, which can make their analysis particularly challenging.
To learn more about the importance of biotherapeutic analysis and how automation can help address some of the associated challenges, Technology Networks spoke to Sudharshan Rangarajan, product management specialist, Lab Automation, Thermo Fisher Scientific. In this interview, Sudharshan also discusses how laboratories can overcome some of the hurdles of incorporating automation into their workflow and highlights some of the solutions that Thermo Fisher Scientific offers in this space.Anna MacDonald (AM): Can you describe some of the main ways biotherapeutics are characterized and why analysis is so important?Sudharshan Rangarajan (SR): Biotherapeutics consist of large and complex molecules compared to their chemically synthesized counterparts (small molecule drugs). Although the large surface area of these molecules translates to highly specific interactions with the drug targets, their size and complexity make for more challenging characterization techniques. Some of the main characteristics that are typically analysed in biotherapeutics include:
1. Protein glycosylation analysis.
2. Protein aggregation analysis.
3. Host cell protein analysis.
4. Biomolecular interaction analysis.
The analysis of the characteristics mentioned above are accomplished by a whole array of techniques including:
Hydrophilic interaction liquid chromatography (HILIC).
Two-dimensional liquid chromatography.
Capillary electrophoresis (CE).
Reversed-phased liquid chromatography.
Size exclusion chromatography.
Mass spectrometry (MS) techniques can be coupled with most of the techniques mentioned above.Analysis is very important, and this includes complete characterization of biotherapeutics which is performed at all stages of the discovery and development process. It is important because knowledge of product consistency, safety and efficacy are transferred across the entire pipeline. Stress conditions, manufacturing processes and storage affects protein structure and often leads to stability issues as well as aggregation. Therefore, promising biological drug candidates (those with good therapeutic activity and stability) in the early stages of the discovery pipeline are chosen for in-depth characterization.
This is where automation can be implemented. Consistency in data (no variability between sample replicates in terms of results) which is one of the main benefits of automation can be very valuable here.AM: What makes biotherapeutic analysis particularly challenging?SR: Some of the main reasons biotherapeutic analysis is challenging are as follows:
1. Emphasis on higher productivity which means researchers are forced to screen drug candidates as quickly as possible to increase the chances for reaching clinical trials.
2. Need for reduced time and cost in the drug development cycle which puts a lot of pressure on analytical methods and processes.
3. Advanced biotherapeutics that are more extensively engineered that adds to structural complexity.
4. As the complexity of the biotherapeutic increases, higher probabilities for post-translational modifications as well as molecular heterogeneity occurs which necessitates being able to control these modifications.
5. Protein products are typically found in cell media which is often very complex making identification of the protein products challenging.
6. Traditional analytical techniques which are suitable for small molecule drugs are unsuitable for large molecules and so there is a need to investigate new techniques. With large molecule biotherapeutics, the assays are sequential whereas in the case of traditional small molecule-based screens, the assays are parallel.
Therefore, it is imperative that researchers working with biotherapeutics employ various analytical technologies to characterize these large molecules.AM: Can you highlight some of the reasons companies in this field are wanting to automate? How has the COVID-19 pandemic contributed to this?SR: Today, there is a high demand for flexible as well as standardized automation solutions in the field of analytical sciences. There is also a need to maintain high productivity as well as reduced cost and time for biotherapeutic drug discovery and development processes. The COVID-19 pandemic has only highlighted this need even more with laboratories across the world having to maintain minimum number of personnel while following social distancing protocols and still having to continue being productive. Laboratory staff have limited time to spend in the lab and therefore monitor these processes. This results in the need to have automated analytical systems running unmonitored during off hours.
Up until a few years ago, the field of analytical science was dominated by partially automated systems. The presence of fully automated systems was specific to particular applications. This often resulted in islands of automation which were disconnected from each other and required human intervention. Furthermore, in contrast to high-throughput screening systems, a demand for flexible automation solutions for analytical processes exist because of highly complex workflows and frequently changing processes with numerous subprocesses. Labware used for analytical processes are not standardized with various shapes and volumes being used.
Laboratory automation can solve the majority of these challenges and benefits analytical researchers immensely with other improvements like data reproducibility, data tracking as well as reduced hands-on time for staff who would be able to focus more on the results rather than performing the experiments itself. Standardization of containers is important for automation workflows too as most of the automation friendly instruments as well as robotic movers handle SBS plate formats.
AM: Are there any hurdles labs looking to incorporate automation into their workflow should be aware of?SR: One of the main hurdles of incorporating automation into existing manually focused workflows is the challenge of transitioning from manual to automated workflows. Researchers and other laboratory staff must think about how their existing workflows would have to be altered to fit automation. Budgetary requirements and other considerations like space must be taken into account when planning for automation and this could pose some challenges for certain labs. This is especially the case in smaller labs who do not have the experience of working with automation instruments previously.There is also the myth that new technologies and the accompanying methods of doing things are fraught with difficulties and have a steep learning curve. Todays automation instruments are increasingly user friendly and offer good flexibility. The user interface for these systems have become very simple and learning how to automate these instruments is relatively simple with minimal time needed from the staffs side.Another hurdle is the notion that automation instrumentation needs a certain level of programming knowledge to operate. This is not true! Todays software is simple with point and click, drag and drop interfaces. Thermo Fisher Scientifics suite of automation hardware and software products are built with the scientist in mind. There is absolutely no need for programming knowledge to use or even master the use of these instruments. Case in point being Thermo Scientific Momentum Workflow Scheduling software. Momentum is a dynamic scheduling software which enables laboratory automation users to design complex workflows with multiple processes efficiently and easily. The availability of the flow controls feature in Momentum is the perfect example of how users can make instruments perform complex tasks with absolutely no programming knowledge.
Finally, the pricing or the perception of how much automation technology costs! Automation instrumentation is far more affordable compared to what it was a few decades ago thanks to improvements in technology. It is important for customers to keep in mind that in order to perform a cost-benefit analysis, the big picture must be considered. With automation some of the direct financial benefits include:
Reduction in experimental errors.
Improving reproducible results.
Ability to scale.
Decreasing full time employee hands-on-time.
AM: Can you tell us about some of the automated analytical technique optimizations and automation solutions that Thermo Fisher Scientific offers in this area?SR: Laboratory automation is evolving with advancements in instrumentation and software. Accelerated by the recent pandemic, strategic discussions on how to embrace automation and digital transformation have consumed the industry and highlighted the need for diverse and connected solutions. It gave rise to new improvements in the field to ensure business continuity without compromising on productivity and data reproducibility.
Thermo Fisher Scientific offers a range of solutions in the analytical science field. The Thermo Scientific Vanquish UHPLC Loader is an end-to-end analytics workflow solution that enables seamless integration between upstream sample preparation and downstream analysis with little to no human intervention. All the steps in the analytical workflow can be integrated using Thermo Fisher Scientifics laboratory automation products. This complete workflow automation solution provides better productivity, enhanced reproducibility and data tracking thereby paving the way to a fully connected laboratory.
The Thermo Scientific inSPIRE Collaborative Laboratory Automation Platform integrates everything you need for your scientific workflows. With modularity and flexibility being foundational to its design, the inSPIRE platform provides a scalable solution for laboratories looking to realize the throughput, efficiency and reproducibility benefits of automated workflows.
Our industry-leading Thermo Scientific Momentum Workflow Scheduling Software enables users to define, execute, and monitor scientific processes and workflows in a powerful yet easy-to-use visual environment. Whether connecting instrument loaders, workstations or a complete transformative automation system - Momentum provides a seamless user-driven interface and dynamic digital connectivity for end-to-end scientific workflows. With built-in data tools, it helps to connect to a labs software ecosystem for bi-directional data transfer, thus making it a powerful software to achieve new levels of automation performance
Thermo Fisher Scientific also offer the only SCARA type (Selective Compliance Articulated Robot Arm) lab automation robot with integrated vision-assisted teaching, barcode reading and 4-axes of motion the Thermo Scientific Spinnaker Microplate Robot. Features such as plate detection, built-in error recovery, automatic stop with unexpected collisions, built-in plate re-orientation and de-lidding, all work together to ensure the robust delivery of your results.
Automated incubation needs in all cell culture applications can be met by the Thermo Scientific Cytomat Incubator series, which includes features such as precise humidity control, expanded temperature range, automated decontamination routine, TRUE orbital shaking and CO2 control to support high capacity and quality cell growth.
In addition, Thermo Fisher Scientific provides several solutions in the field of analytical sciences including Thermo Scientific Chromeleon Chromatography Data System (CDS) software, Thermo Scientific BioPharma Finder software, Thermo Scientific Zeba Spin Desalting Columns, Thermo Scientific Pierce Protein A Columns, Thermo Scientific NAb Protein G Spin Columns and kits like Thermo Scientific EasyPep 96 MS Sample Prep Kit as well as Thermo Scientific SMART Digest Proteinase K Kits.
AM: Do you have plans for further developments in biotherapeutic analysis that you are able to share?SR: There is tremendous demand in the field of analytical sciences for automation solutions. Specifically, we see this in the area of biotherapeutics workflows/large molecule workflows with several projects done in this area. These massive projects are mostly custom solutions that we offer by working closely with our customers from the beginning of the project all the way to completion.
Though we still have the capability to support these custom project type solutions, we are planning to offer these solutions as standard bundles with routinely used instruments for these large molecule workflows. We are in the plans of offering these standard bundles in conjunction with other business units in Thermo Fisher Scientific making use of their expertise in the process. This will enable customers to access turnkey solutions that enable them to start working with minimal down-time.
Sudharshan Rangarajan was speaking to Anna MacDonald, science writer for Technology Networks.
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The Rise of Automation in Analytical Science - Technology Networks