High-throughput screening is a mainstay for cell line generation. However, the complex instruments used for high-throughput methods have many moving parts. Automation can streamline and accelerate the process. By minimizing human intervention, sophisticated software can simplify workflows, decrease errors and free up laboratory staff for other tasks.
Still, early efforts to automate this process have often fallen short. Scientists have to circle back frequently to handle plates, reprogram software and ensure the process is running smoothly. Once the instruments have identified potential hits, users must again step in, transferring these promising wells to lower-density plates for further growth.
This persistent need for human intervention can put entire runs at risk. If users select the wrong transfer map, sending potential hits to an incorrect destination plate, the run may have to be scrapped, and the team has to start over.
Automation scheduling software, a new class of automation technology, gives users full control over scheduling and imaging. Such products, like Green Button Go automation scheduling software from Biosero, automatically collect confluence data and analyze those values, hit-picking and seamlessly transferring those hits to the next instrument.
Ease of use drives efficiency
This kind of software is advantageous because it helps biotech researchers automate high-throughput screening. Effective software will have an easy-to-use interface so that operators can work from a single screen to start a run. After that, they may not have to intervene until it’s time to collect results.
Operators can readily schedule imaging days for multiple groups, assign group IDs, set start times, indicate quantities for source and destination plates, select storage incubators and provide confluence thresholds to identify hits—all using components of the software. It also gives researchers the ability to push imaging data to the company network for safekeeping and analysis.
Researchers can select which days they want to run an image and specify text strings to link plates together. Software that supports multiple users is best because co-workers can order the transfer of plates from the incubator to the imager at specified times or simultaneously. Using different group IDs and cell lines, they can ensure these expensive systems operate at their highest efficiency.
For maximum efficiency and flexibility, utilize device-agnostic software. When device-agnostic automation software is used in the lab, engineers and scientists have the freedom to choose the instruments and equipment best for their scientific method, and are not limited to the same vendor for equipment and software.
Automatic hit transferring
After sample imaging has been completed (See Figure 1), software compares the confluence goal assigned by lab operators during the initial setup with the imaging results. Based on this analysis, it selects the most successful cells and transfers them from 384-well to 96-well plates, giving them more room to grow as well as reducing the number of days to analyze, expediting processing.
Software with an image evaluation feature can identify wells that exceed the confluence threshold and add them to a transfer list, generate an imaging report file (See Table 1) and assess how many destination plates are needed. Data in the ensuing report includes barcoded timestamps, well locations and the confluence value for each well on the source plate.
In addition to automatically evaluating whether there are enough hit candidates to fill the required destination plates, automation software assigns higher priority to the source plates with the most hits, automatically processing them first.
Software is also effective and efficient because it can create a list of candidates and convert them into a transfer map for the liquid handler, which applies the map automatically. As a result, users don’t need to worry about selecting the wrong maps and possibly dispensing samples in an incorrect destination plate.
Keep close track of source and destination plates, as well using automation software. If the liquid handler can only hold two destination plates—but needs five—software can be configured to schedule additional runs to fill the necessary destination plates. It can also assess whether a source plate has already been processed while the destination plate still has empty wells, allowing it to take cells from a different plate. Throughout the process, data is driving decision-making.
Many labs must keep pristine digital records to maintain 21 CFR part 11 compliance. If that is a requirement, look for automation software that is available in a version that is 21 CFR part 11-compliant. This means the software includes features to enhance data security and closely track the chain of custody to simplify audits. For instance, administrators can set user permission levels, control password rules and expiration, and record log files and timestamps for each login or attempted login.
The fruits of automation
The mechanics of cell line generation are complex, but they don’t have to be all-consuming. Well-designed software can automate the process from scheduling all the way through imaging, data analysis and cell picking, freeing up researchers to plan and analyze valuable experiments.
Utilizing automation scheduling software provides additional walkaway time and boosts efficiency in the lab. Lab technicians will spend less time parenting the cell-picking machinery, and can confidently perform other tasks while the software takes on the rote processes. The reduced human intervention also lessens the risk of mistakes.
Together, these refinements improve the efficiency and quality of work life in the lab, make the cell line generation process run more smoothly and produce better results.
Darren Arney is a field applications scientist at Biosero, a company that creates “future-proof” software platforms. There he bridges the gap between the goals of the scientific method and the vast technical capabilities of the company’s flagship Green Button Go automation scheduling software.
For more about the Green Button Go product, visit www.biosero.com/products/green-button-go