When “every sample is a life trusted to our care”*

How Artel technology played a critical role in CRL’s exceptionally fast development and scale-up of a saliva-based SARS-CoV-2 assay to meet the unprecedented testing need.

5 Short Months

From having a manual, saliva-based qPCR assay to a production assay and the infrastructure to test tens of thousands of samples a day.

From 1 to 17 ALHs

CRL rapidly qualified and brought an additional 17 automated liquid handlers (ALHs) into production to deliver SARS-CoV-2 testing at the scales needed to make an impact.

Immeasurable Impact

While the MVS enabled the rapid launch of a novel testing service increasing revenue, the true impact has been on meeting the critical public health needs.

Product used: MVS® Multichannel Verification System
Applications: Calibration, Assay Development, Assay Troubleshooting, Assay Transfer

SITUATION

Faced with the onset of the COVID-19 pandemic in the US in February 2020, Clinical Reference Labs (CRL) realized that they had the resources and capabilities to make a difference, and set out to develop a qPCR-based SARS-CoV-2 assay that could use self-collected samples.

In just a few months, they identified saliva as their desired sample type, developed an assay, and obtained Emergency Use Authorization from the FDA.

CHALLENGE

While CRL originally developed a manual assay, they knew they would need to automate their assay and scale throughput to provide the amount of testing that their clients were requesting, as well as to have a positive impact on public health and safety due to the lack of available testing.

But converting a manual assay to an automated one can take time. In addition, the molecular diagnostics lab at CRL needed to build out their lab’s infrastructure, which started out as a single ALH and 2 qPCR instruments. Qualifying each instrument would take time, but the community needed increased testing capacity as soon as possible.

SOLUTION

CRL’s newly hired Director of Technical Laboratory Services, Rob Grbac, knew right where to start. As he was already familiar with the Artel MVS, he brought one in-house to ensure data integrity and that all the ALH’s were optimally performing and to accelerate the assay transfer and assay troubleshooting processes.

For example, when the molecular diagnostics lab could not get a critical step to deliver results within desired specifications, they were able to use the MVS to quickly identify which step in the assay was causing problems, find a solution, and get the high-throughput instrument into production.

With the MVS, CRL is able to ensure quality results while rapidly producing trusted SARS-CoV-2 test results.

The CRL team knew that they could really make a difference

When the threat of the COVID-19 pandemic was really starting to come into focus in February of 2020, the team at Clinical Reference Labs (CRL) took a look at their resources and realized that they were uniquely positioned to have an impact on the public health response. A privately held, family owned and operated company that is currently led by the third generation of the family, CRL had been providing toxicology and general lab tests for many of the largest retail, transportation, pharmaceutical, healthcare, and financial service organizations in the world. They had a small molecular diagnostics lab that would require a large up-front investment to build out if they wanted to provide COVID-19 testing, but the team knew that the clear public health need meant that investment was not just worth it, it was absolutely essential.

Heather Fehling, Ph.D.
Chief Scientific Officer of Molecular Diagnostics, CRL

To really have an impact, they needed an assay that could be self-collected…

The small Molecular Diagnostics team at CRL set to work developing a qPCR assay to detect SARS-CoV-2. In view of the nasopharyngeal swab and medical testing professional shortages, they explored different types of samples with the goal of creating a test based on self-collected samples. After much experimentation, they were able to develop a SARS-CoV-2 assay that avoided many of the bottlenecks and supply issues by testing saliva collected by the patient.

Heather Fehling, Ph.D.
Chief Scientific Officer of Molecular Diagnostics, CRL

But saliva was challenging to work with

The next challenge was scaling, which became the initiative of the newly hired Rob Grbac, Director of Technical Laboratory Services:

“The challenge was to figure out a way to go from a manual assay that could test 300 samples per day to a reliable automated process that could process 30,000 samples per day, while keeping false results to an absolute minimum. However, it was also about automating the entire process and not just the sample prep step. We needed to integrate systems to talk to each other, automate sample tracking from start to finish, as well as to create a platform to get the results to the patient as quickly as we could.”

CRL was up for the challenge and got to work right away but hit a bottleneck right out of the gate. The use of saliva, CRL’s market advantage, as a sample really complicated the process.

As Rob puts it:

“I’ve been in the automation and integration industry for over 16 years and bar none saliva is the trickiest solution I have ever worked with. It is very unpredictable and different from sample to sample. Yet we had to find a way to accurately pipette ‘loogies,’ (excuse me) from our collection device into an automation-friendly plate format without cross-contamination.

Our COVID-19 test stands apart from other tests on the market because it is home collected. But because of that, the collections we receive are not consistent from sample to sample. We get samples that don’t have enough saliva or ones with too much. We get samples that have particulates in them as well as samples where we know the patient ate or drank prior to collecting. We even get adulterated samples where the patient tries to “trick” our systems. We got a batch of samples late summer of 2020 where we clearly knew the samples were compromised.

Luckily we have very smart people here and we created a matrix, dosed the sample to the matrix, and ran it through our LCMS. Come to find out, those samples were all consistent with one factor – all had residual components of mouth wash! We had our speculations, but these patients needed to test negative and clearly took matters into their own hands. Nevertheless, our method and processes were well developed to clearly identify the erroneous samples. This just demonstrated the unpredictability of the samples and the need to develop a robust and rugged method (from sample prep though analysis).”

The MVS helped ensure that pipetting was accurate and precise

Moving saliva had its challenges, but we were afforded some wiggle room because of the large volume being transferred. This was not the case for the Master Mix, but this is where the MVS system accelerated their development.

To ensure that saliva and every liquid in the assay was accurately and precisely transferred, whether it was 5 µL or 500 µL, Rob brought an MVS in-house and integrated it into the CRL molecular diagnostics lab. Having previous experience with the MVS, Rob knew that it could not only provide fast calibration and volume verification of the liquid handlers, but that “…the software collects and analyzes the data in a short timeframe and allows us to make critical decisions regarding proactive actions or confirmations regarding what the liquid handlers are doing. It is super-fast and super-efficient.” The MVS also gives you channel and dispense statistics that assist with troubleshooting and optimizing assays, accelerating assay transfers.

Because the MVS provides a real-time analysis report of volume transferred, you can break down complex, multi-step assays into smaller units and determine if the problem is related to liquids being over-, under-, or inconsistently transferred. One of many challenges the MVS helped Rob’s team solve was getting a critical 96-channel ALH into production. They couldn’t get it to perform using the already-developed method, but after analyzing the assay with the help of the MVS, they were able to get the ALH into the production lab the very next day. The addition of that instrument increased daily capacity by 8,000 samples per day so the pressure to get it working was immense.

Now CRL uses the MVS routinely to verify their automated liquid handlers’ performance and to maximize instrument up-time in all labs across the company. From an ALH perspective, they verify that the instrument can transfer the expected volume, but they also look at performance from a method perspective. When they do liquid class development, they use the MVS to optimize the liquid class for each solution.

Rob Grbac
Director of Technical Laboratory Services, CRL

Pivoting a whole company to meet the immediate pandemic threat

Developing a robust SARS-CoV-2 assay that could be easily collected at home by the patient was a huge challenge that brought together many different teams at CRL. That they were able to accomplish so much in just 5 months and with large up-front investments of time and resources, including a dramatic expansion of their world-class molecular diagnostic lab, speaks to the company’s core values and commitment to the community. Artel is proud that the MVS is a small part of CRL’s tremendous achievement.


*One of Clinical Reference Lab’s (CRL’s) core mottos

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