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Adaptable, Accurate and Affordable: The Next Wave of BTLAs

Wouldn’t it be great to turn on the lights and discover right-sized, perfect throughput, custom-designed instruments in your own lab? The latest benchtop automation devices, using space-saving components and open source software, offer endless possibilities for small and mid-sized labs to increase throughput while decreasing costs.

Felix Lenk, Ph.D., watched as students jockeyed for space and labored over basic, repetitive research processes in the crowded lab at the Technische Universität Dresden, Bioprocess Engineering (TU Dresden ILB), Dresden, Germany. He wondered about creating a machine to do the tasks.

“I studied automation and control, so I am always thinking about how to automate a task that I am doing for the third time,” he says with a laugh. “Ready-made systems available for these tasks were capable of running 1,000s or 100,000s samples per day, but there weren’t many medium-throughput automation solutions available to manage 500 to 800 images per day that would fit on one standard workbench.”

This inspired Lenk and his team to develop a new compact benchtop laboratory automation system (BTLA), the PetriJet platform, a network of exchangeable processing stations that provides automated handling of culture dishes in batches of 20 or continuously up to 1,000 dishes through preparation, incubation, imaging and analysis. Lenk estimates that his lab automation solutions typically increase sample throughput times by four while cutting down labor costs by approximately 75 percent. By leaving the source code on his devices open, Lenk’s BTLAs have an added bonus of being adaptable for many laboratory needs.

He describes the system as “a workhorse in the lab.” For example, the P.CAM360 digital imaging station takes 3,000 images per week. “If you think about the throughput of about 100 cartridges per hour, you get an idea of how many hours this system is in use," says Lenk, who is department head of TU Dresden’s SmartLab Systems group at the Institute of Food Technology and Bioprocess Engineering.

A Petri Dish Revival: Conquering Medium-Throughput Automation

Lenk had a few inspirations in automating his lab. The medium-throughput environment focused on samples cultured in Petri dishes, and all over the lab everyone was taking pictures of the samples at various stages of development. One enthusiastic Ph.D. student took 4,000 images of biological samples during two weeks of research. “I asked her if she had been here on Saturdays and Sundays. She said yes. She also took photos morning and night,” he recalls. To begin with, Lenk thought that he could make a nice system to take better images. What developed was P.CAM360, that stationary digital camera apparatus that scientists could use to take high quality images of Petri dish contents. But he didn’t stop there.

“What we needed was a platform to transport culture dishes as the user would do: pick up the sample from the incubation device, move it to the bench, put a new medium in it and take images of it," Lenk explains. “This would not be an ordinary, off-the-shelf instrument.”

He conducted a very informal investigation into Petri dish use and discovered that many researchers shifted from deep well plates to Petri dishes, but wanted to maintain the level of throughput they had with a 96-well plate. “Five years ago, people worked with single cells in multi-well plates, but single cell behavior is quite different from how it interacts in a broader cellular environment with other microbial elements in a Petri dish culture,” Lenk explains. While multi-well plates offer the opportunity to do many experiments in parallel and keep the process moving through automation, Petri dishes offer a robust view of the cellular environment.

“The solid medium in the Petri dish offers you several advantages. The boundary layer of the solid medium creates a good environment for cell culture, especially with tissue cultures, as it offers access to nutrients from below and air above,” Lenk explains. He anticipates that working with Petri dishes will become more and more important because of this and would like to see that research institutions dealing with high culture development would add a system for handling Petri dishes.

He decided that his team’s system would offer a compromise for researchers not content with the lack of automation for Petri dishes or the limited cell environment imposed by the 96-well plate. Initially, they considered incorporating components from industrial automation into the system, but found that this option didn’t offer the technical sophistication they hoped for, not to mention the pieces were cost-prohibitive and over-sized. “Our lab did not have those dimensions. We would have needed a whole other room to house the automated portion we were considering,” he explains.

The team instead turned to open source design solutions available on the web, employing Arduino microcontrollers, Raspberry Pi general purpose microcomputers and a Reprap rapid prototype device that 3D printed parts needed to create the PetriJet platform.

The components that developed include the PetriJet, which uses a multi-functional mechanical gripper to perform various tasks in conjunction with different processing stations, while also transferring samples from one culture dish to another; the NutriJet, a fully automatic system which produces nutrient medium right from its ingredients; the P.CAM360, which completes imaging; and another station that features real-time, stereo imaging with integrated software that allows a reconstruction of a 3D image and extensive image analysis for parameter extraction. The configuration and operation of this compact device can be browser-based using a smartphone or tablet PC. In addition to these components, Lenk’s group is currently working on a processing station to fill empty culture dishes with nutrient medium.

Lenk recently discussed the BTLA system in an SLAS Webinar, “The SmartLab of the Future: Benchtop Lab Automation with the PetriJet and NutriJet Platforms,” and authored a paper on the topic, “PetriJet Platform Technology, An Automated Platform for Culture Dish Handling and Monitoring of the Contents,” for the Journal of Laboratory Automation (JALA), one of two official SLAS scientific journals.

When other labs within TU Dresden, from microbiology and plant breeding to the university’s wood and fiber lab, saw how the system performed, they quickly adopted the technology. The escalating workload resulting from these demands led to the recent spinoff of SmartLab, Lenk’s group of seven TU Dresden biologists and bioprocess engineering specialists who only do device development. “It is a support unit, but it’s not like a contractor,” he explains. “We study the engineering side of a bioprocessing problem, look at the research the scientist is doing, gather input as to what the limiting factors might be in terms of throughput and accuracy and translate that into a new automated device.”

On the commercial side, SmartLab sold two devices to a drinking water analysis laboratory. Lenk explains that once a year throughout Germany households submit drinking water samples to be analyzed for legionella. Lenk’s group developed automation to move culture dishes through the incubation and examination process. He estimates that by year's end, a system to manage 1,500 culture dishes in an eight-hour shift will be in place.

Open Source Automation

Examining how BTLA systems can save money, time and lab space, as well as become more reliable, precise and adaptable, is not limited to TU Dresden. It’s something that Sam Michael also studies in his role as director of automation and compound management at the National Center for Advancing Translational Sciences (NCATS), Washington, DC.

“Benchtop automation is becoming more realistic,” comments Michael, whose group of automation engineers and machinists maintain, operate and continuously improve a full range of laboratory instrumentation and processes that support NCATS activities in high-throughput screening, assay development and optimization. “I think BTLAs powered by open source design offer more flexibility and the ability to customize – especially in a community such as SLAS, where everyone’s lab environment and needs are different,” he continues.

Michael admires Lenk’s work and refers to him as a trailblazer for using open source design in his devices. When Lenk’s abstract proposal on BTLAs crossed his desk, Michael recruited him as a presenter for SLAS2016’s Automation & High-Throughput Technologies Track in the Screening Automation: Modular Systems vs. Highly Integrated Systems session entitled, “The Internet of Things and Benchtop Lab Automation Systems Bring You into the SmartLab of the Future A Case Study of Ongoing Process Developments.”

“Felix and others like him are taking the black box element away from the instruments,” says Michael. “From my perspective, I love that. What frustrates both end users and people supporting instruments is if the device is a black box, they have no idea of how to modify it just a little bit. Now with these capabilities, it’s easy to augment what an instrument is doing.”

Michael thinks there is a push for automating and adapting equipment in all types of labs from screening and diagnostics to even some chemistry functions. “Even if the biologists are not familiar with the technology, there usually are people on staff who can get them started in the automation process,” he comments, adding that the do-it-yourself attitude of the maker community is touching all areas of life sciences discovery and technology making it possible to adapt existing instruments or build your own.

“It’s affordable to have a 3D printer in your lab. It’s even more affordable to use drafting software to draw a spare part and send the resulting stereo lithography (STL) file to a service that 3D prints the part for you with a quick turnaround time. It allows laboratories to go their own way and actually learn how to put these things together,” comments Michael, whose own lab developed an Arduino to monitor the lab’s freezer inventory. “It’s an incredibly low-cost solution versus spending tens of thousands of dollars on freezer tracking software.”

Michael equates the increasing comfort level with open source BTLAs to the adoption of smartphone technology 10 year ago. He believes that mobile devices helped other complex, yet user friendly, technologies gain popularity. “Most people became comfortable with it in a relatively short amount of time,” he says. “It’s the same with laboratory automation."

The next generation of life sciences discovery and technology professionals are likely to double the size of that comfort zone, he continues, "as they have spent their entire lives with gadgets so they are at ease with the concept of automation and how to work with open source code. Even more established scientists regard it as just part of their daily lives. It’s more accessible.”

In this area, he cites drone companies as influencing life sciences discovery and technology professionals. “What drone companies realized is that where open source ties in is within their huge user community which is incredibly intelligent and not only wants to use their product, but also wants to improve it by adapting the code,” Michael explains. “Instead of making a closed platform, they put it out to the community and let them design their own tools. You end up getting unbelievably robust packages, completely designed by users, which help move technology forward. It’s a crowd sourcing of expertise over time that helps the software get better for everybody.”

It is a process used to fuel the National Institutes of Health 3D Print Exchange, a resource under the direction of Project Manager Meghan Coakley, Ph.D., who recently contributed a paper to a JALA Special Collection on 3D printing in the laboratory. “If we develop something, Meghan puts it on the exchange for everyone to explore,” says Michael.

The mission of the print exchange is to provide access to high-quality, scientifically accurate 3D-printable files related to bioscience and medicine. The database, tools and sharing features help make this possible. To fully maximize the potential of the site and its content, the exchange created an application programming interface (API) that provides a gateway to its open architecture, for better sharing content across other 3D printing communities and resources on the web.

"The journey and the process researchers follow to get to scientific discoveries using the 3D printing exchange are just as important as the end results," comments Coakley, who is also the program lead in the Bioinformatics and Computational Biosciences Branch at the National Institute of Allergy and Infectious Diseases. "When we first launched the website, NIH Director Francis S. Collins, M.D., Ph.D., said that 3D printing offered an incredible return on investment, that a pennies' worth of plastic has helped investigators address important scientific questions while saving time and money,” Coakley continues. “That continues to be the story of the exchange. NIH uses 3D printing to create a physical object from a digital model to study viruses, repair and enhance lab apparatus, and help plan medical procedures.” She adds that the 3D Print Exchange makes these types of files freely available, along with video tutorials for new users and a discussion forum to promote collaboration.

Employing Prudence

With such an open forum comes greater responsibility to protect aspects of research and data that are proprietary.  Both Lenk and Michael note the cautionary side of open source software. Michael comments that malleable software can become a potential support nightmare for instrument companies. "While we may love having complete open source software that we can tweak and modify to add a capability or change functionality,” he explains, “we end up with software that isn’t quite under the instrument company’s control because of modifications."

Lenk adds that the moment free and open source software (FOSS) moves into a commercial application, the software developer wants to collect the licensing fee. "Open source is perfectly suitable for universities," he says. "They can start building what they want because everything is free, but if the instrument moves into a spin-off in the market, you are going to have to review its entire software.”

"It brings you to difficult position when someone wants to buy this system from you," says Lenk. "It’s difficult at that point in development to go through all the software and see if you are working within the licensing agreements. You can get into big trouble in no time."

August 2, 2016