What is Cherry Picking?
Those who work either with DNA/RNA, cell lines, drug discovery, or proteomics while using microtiter plates have most likely come across an expression called “Cherry picking or Hit picking.” So what is Cherry picking, and how is it done in practice? In a nutshell, it involves selecting the most promising or positive samples with specific characteristics from a larger set and transferring them from a source microtiter plate or vials (tubes) to a target microtiter plate for further evaluation. While Cherry picking is conceptually simple, executing it properly demands a high level of precision, accuracy, and effective traceability.
Cherry picking in different workflows
Cherry picking is most commonly used when doing high throughput screening using 24-, 96-, or 384-well microtiter plates. It finds application in various fields, including drug discovery screenings (e.g., small molecule candidates), cell line development (e.g., modified production cell lines in pharma), genomic studies (e.g., clone library construction and screening), proteomics (e.g., protein identification), and other life science workflows.
Challenges
Cherry picking is often performed manually by highly skilled lab personnel who transfer samples from the source to the target plate positions. This process demands careful planning of the experiment, precision to avoid contamination or sample loss, and accurate sample transfer to the designated positions on the target plate. For instance, this might involve transferring a sample from position G7 on a 384-well source plate to position B10 on a 96-well target plate.
Additionally, manual data recording can introduce human errors and make it challenging to establish a clear audit trail. This not only affects traceability but also hinders real-time data updates for monitoring experiment progress. Consequently, it elevates the risk of data misinterpretation, potentially compromising the integrity of research outcomes.
In this context, digitalization has revolutionized the Cherry-picking methodology, transforming the way life science experiments are conducted. With the adoption of digital tools like Pipetting Aid PlatR, researchers can streamline the entire process, boosting efficiency and enhancing traceability. Digitalized processes facilitate automated data recording, enabling real-time updates of sample transfers and experiment progress. Electronic recording of each carefully selected sample greatly enhances traceability, allowing authorized personnel to access, review, and validate data easily. Notably, barcodes have become an integral component in enhancing traceability.
Figure 1: Manual transfer of samples using a barcode reader and PlatR
With advancements in technology, liquid handling instruments and other support devices are increasingly utilized to facilitate and automate laboratory processes. These technologies not only enhance accuracy and precision but also significantly boost experiments throughput. However, it’s important to note that not all laboratories have the budget for liquid handling instruments. Additionally, these machines have certain limitations. They often require substantial time and effort for programming, which can be impractical for non-routine tasks. Liquid handling instruments may encounter difficulties when pipetting viscous liquids or very small volumes. Furthermore, not all tasks can be automated, necessitating manual pipetting by lab personnel to transfer samples from source to target positions.
Cherry picking in practice
When it comes to transferring samples from the source to the target position, cherry picking can be accomplished in two ways:
- Transferring selected samples from a tube (vial) to a microtiter plate
- Transferring selected samples from a source microtiter plate to a target microtiter plate
Each approach comes with its own set of challenges.
Transferring samples from tube (vial) to plate
A common scenario is when you have to transfer a sample from a tube to multiple positions on a microtiter plate. In this case, a user has a set of samples in the tube rack and manually pipettes samples to designated positions on a microtiter plate. Even an experienced laboratory staff can make mistakes, either when selecting the correct sample from the rack or when placing it in the correct well(s) on the microtiter plate(s). The use of barcodes to distinguish between samples can significantly enhance accuracy and simultaneously provide sample traceability.
Figure 2: Transferring samples from a tube to a microtiter plate
To address the most common mistakes occurring during sample transfer, we developed a dedicated module in our pipetting tool, PlatR. This module enables a guided transfer of samples with respective barcodes to designated positions on 96-well or 384-well plates. The process involves scanning a barcode, which is matched with the correct position on a predefined pipetting plan. An illuminating light beneath the matched well guides the user on where to transfer the sample. This guided process also automatically logs each action performed by the user, greatly enhancing traceability.
Transferring samples from plate to plate
When transferring samples from one plate to another, a common scenario is a high-throughput screening, where selected samples with specific characteristics need to be transferred for further processing. For example, you may need to transfer samples from more 384-well plates to a 96-well plate. In this case, a user needs two plans: one for the source plate specifying designated well positions and another for the target plate, indicating the desired destination for selected samples, as illustrated below. This process can be tedious, time-consuming, and prone to errors. Therefore, leveraging digital tools and liquid handling instruments can significantly enhance efficiency, traceability, and long-term cost savings.
Figure 3: Transferring samples from more 96-well plates to one 96-well plate
Summary
Cherry picking, remains a vital and indispensable methodology in life sciences for selecting relevant samples from cell lines, drug discovery, genomics, proteomics, and other experiments. This process has undergone a remarkable transformation, leading to increased efficiency and heightened traceability.
Embracing digital tools not only streamlines Cherry picking operations but also empowers researchers to make well-informed decisions, accelerating scientific discoveries and advancements in the life science field.
