AVENIO Edge System

Meet Manuel and Aria, two lab techs with different approaches to next-generation sequencing sample prep, manual versus automated. Today, we are putting their approaches to the test to see who is using their time most efficiently.

With the score at 0-0, it is the beginning of another busy week. And both start in a similar fashion: sorting, labeling and aliquoting samples that need exome sequencing this week. With that administrative task out of the way, these samples are ready to go into library preparation. And so far, there are no differences between the two labs. As Monday comes to a close, Manuel is finalising his workflow parameters and preparing his sample tracking sheet, while Aria loads her first library prep run on the AVENIO Edge system. While she's away, her samples will become barcoded libraries, while Manuel's lab work comes to a halt.

The next morning, Aria returns to find the AVENIO Edge has finished processing her first 48 samples. She is strategically prioritising library prep to later multiplex and run a high-throughput target enrichment run. Manuel, on the other hand, continues his slow, monotonous manual method of pipetting and loading samples little by little, missing out on important things throughout his day. like catching up on e-mail and proper break times. That is another 48 libraries for Aria. A total of 96 to Manuel's 24. All Aria has to do now is load another 48 samples onto the AVENIO Edge, which will again work overnight. That makes 96 samples prepared in one day. Another day done and it is clear that automated NGS sample prep is more efficient than manual.

Looks like Aria has now pooled her 144 libraries and is loading her first target enrichment run. Poor Manuel. His hands have got to be feeling some fatigue from all that repetitive motion. It does make one wonder if his samples could be suffering also. Aria, on the other hand, has walked away with confidence while the AVENIO Edge processes her samples. She is able to do more with her time, like look at bioinformatic analysis or collaborate with colleagues. It is hard to watch, really. Poor Manuel has been absolutely held back by outdated and inefficient tools, having processed only 64 libraries that are just starting target enrichment. While Aria's target enrichment run of 144 samples finished earlier today, she is now loading another library prep prior to loading the sequencer.

Manuel finally gets to sequencing his first batch of 64 samples. Still, it is no comparison to Aria, who has already finished sequencing 116 samples. With this contest nearly over and Manuel's inferior manual method soundly defeated, Aria exhibits a show of good sportsmanship by showing Manuel there's a better way. She loads an end-to-end library prep and target enrichment run of 24 samples. The AVENIO Edge will work non-stop over the weekend, so these samples will be ready for sequencing come Monday morning.

The numbers speak for themselves, ladies and gentlemen. With the AVENIO Edge, automated NGS sample preparation is far superior to manual methods. Reconceptualise the workweek. Spend your time where it matters.

David Gonzalez de Castro, PhD FRCPath, co-director of the Precision Medicine Centre of Excellence and professor of genomic medicine at Queen’s University Belfast:

The Precision Medicine Centre, we call it the PMC, here at Queen's University Belfast, was first established in 2018 with the long-term goal of creating a clinical research facility, bringing together genomics, digital pathology and big data analytics into seamless integrated workflows to support industry, healthcare and academia collaborations into diagnostic services for cancer patients.

Our facility is an ISO 15189-accredited service and has a unique hybrid infrastructure where we work collaboratively between healthcare, academia, the university, the Northern Ireland Biobank and our industry partners. Our long-term vision here is for all Northern Irish cancer patients to have access to comprehensive genomic profiling and integration with digital pathology. By achieving this, we expect to accelerate the diagnosis and the delivery of tailored therapies to patients individually for them and improve their clinical management.

With our genomic laboratory workflows, we are able to achieve a three-week turnaround time from biopsy to genomic profiling. This is a big deal because right now, in most decentralised facilities, you would expect to have anywhere between 6 to 8 weeks turnaround time from biopsy to a comprehensive genomic profile. Our fast turnaround times mean that more timely decisions can be made for the benefit of patients.

The genomic approach we use here at the Precision Medicine Centre has allowed us to identify new alterations in tumour samples that we were previously not testing for. This has allowed us to identify new patients with biomarkers that can access now targeted treatments that were not available otherwise. The diagnostics team here have tested already about 3,500 samples in the last 12 months, which is basically all the tumour samples that come through the door per year.

In 2020, we partnered with Roche and Sunray Analytics to establish the Action Consortium with funding from Innovate UK, part of UKRI. The project was set up to develop an integrated genomics and digital pathology algorithm that will predict colorectal cancer patients that are at very high risk of recurrence following surgery with curative intent.

Roche has supported action, providing samples, data and instruments, and combining state-of-the-art NGS automation and digital pathology platforms into a seamless workflow. Realising our synergies, this was an ideal opportunity to showcase how combining both disciplines could provide better clinical information and therefore better clinical care.

The emergence of the global pandemic soon after the initiation of our collaboration meant that all projects came to a halt, including Action. We lost two out of the three years of the project, and it has been a major achievement to get us back on track and clear all the backlog in the last 12 months. In January 2022, none of the first 300 samples from the Action project had been analysed. We were relying on three members of our staff to do manual preparation, which was a very big ask for them and a very big risk for the project. That started to change when the AVENIO Edge system arrived.

Peter Stewart, PhD, scientific lead at Precision Medicine Centre of Excellence for Genomics:

We were the first clinical research laboratory in the world to install an AVENIO Edge instrument. When I started in the PMC in January 2022, I was assigned to implement the instrument and get it validated. From our experience, we know there can be significant challenges working with automated liquid handlers. Whether that is the different protocols that the system can run, reliability issues, or the need for detailed, lengthy staff training to deal with complex programming. In fact, it had taken our team approximately 2 years to iron out reproducibility issues with the existing liquid handler.

But with the AVENIO Edge, we found setting up and validating the system very straightforward. The system was installed in a week, and the initial training was performed over a week. After that, we were able to run some verification samples. We did the comparison across a number of different runs, and when our external collaborators showed us the analysis, we were really pleased to show a high concordance between the manual preparation and the automated workflow.

Automated sample preparation using AVENIO Edge has allowed us to clear the backlog of action samples within just 14 months. It would have been impossible for us to process all those samples using manual preparation methods within the project-defined timeline and the available staff resources.

The instrument offers validated research protocols, end-to-end sample and consumable tracking and on-board quality control capabilities. It allows the user to walk away and leave it working. This not only eliminates the need for repetitive, time-consuming manual pipetting and other hands-on tasks, it also means that we can run sequencing workflows virtually 24-7, which extends our labs, throughput and capacity. And at the same time, reliability and reproducibility are improved and pressure on the team is reduced.

The AVENIO Edge research use reagents are pre-optimised plug and play barcoded kits. You just take them out of the freezer, thaw and insert them into the machine. Usually, you can spend the first 30 to 40 minutes of each day making up a master mix. It then auto-calculates the number of tips, the acquired reagents and tells the user where to put them on the deck.

Once the system is loaded, the operator just needs to close the front flap and hit start. Before initiating the run, the system carries out a pre-analytical check to make sure the correct components have been loaded. Any discrepancies are automatically flagged up, and the run will not start until the problems have been resolved.

The AVENIO Edge is the best system I have seen around for the ability to track samples and reagents through the NGS workflow. The reliability of the AVENIO Edge has been faultless, so much so that we are now working to develop protocols for other workflows that involve manual prep and looking to transfer sample prep for other sequencing projects over to the AVENIO Edge.

We have been working with a collaborator who has provided us with ctDNA samples in July 2022, and we have ran now in the region of 200 plus samples, ctDNA samples. The amount of ctDNA that we have for each sample is very small. We therefore have only one opportunity to run the ctDNA on a library prep. With the AVENIO Edge, we had the confidence in that reliability that we could run the ctDNA sample, and it would work. So we have a lot of confidence for future ctDNA projects in using the AVENIO Edge.

David Gonzalez de Castro, PhD FRCPath, co-director of the Precision Medicine Centre of Excellence and professor of genomic medicine at Queen’s University Belfast:

Using the AVENIO Edge system, we can free up team members to work in different parts of the project or even take new projects that bring additional value. The AVENIO Edge system has played a vital role in making sure that we can keep our turnaround times in check.

Looking ahead, we want to make sure that more cancer patients have access to comprehensive genomic profiling of their tumours and therefore have access to the full range of targeted therapies available to them.