A Simple Workflow Helps Labs Accelerate Immunotherapy Lead Candidates

How the IsoLight/IsoSpark can support a research lab’s pursuit of novel immunotherapies

Clinical Lab Manager

Labs working on pre-clinical and clinical therapeutics research often find themselves facing numerous shortages. Staff shortages are commonplace. Getting enough funding is always a challenge. There’s never enough time. And even the physical space in the laboratory can be limiting. That’s why clinical labs can benefit enormously from choosing instruments that are multifunctional and automated.

Prime examples are two IsoPlexis systems—the IsoLight and IsoSpark. Both systems have multifaceted capabilities that cover the entire proteomics workflow in a single automated instrument. These two systems support applications for low volume highly multiplexed proteomics, single-cell secreted proteomics, and single-cell pathway omics. The IsoLight has an eight-chip capacity, meaning it can run eight highly multiplexed single-cell or bulk experiments at a time, making this system popular among pharmaceutical companies and core facilities. Meanwhile, the 18-inch footprint IsoSpark can run four experiments at a time, enabling individual labs to perform single-cell proteomics with ease. 

These three applications performed on the IsoLight/IsoSpark can carry a lab developing immunotherapies through an entire week of research, when traditional platforms may take months to years to supply less informative data. The integrated IsoSpeak software is key in accelerating insights into the development of novel therapies by automatically analyzing the data from each application run on the IsoLight/IsoSpark, providing advanced, publication-ready visualizations at the push of a button, without the need for a data informatician. Here’s an example of what that week might look like. 

Day 1: Low volume highly multiplexed proteomics 

The search for immunotherapies often begins with a list of several drug candidates. IsoPlexis’ low volume highly multiplexed proteomics can serve as a global screening tool for the immune impact of lead candidates and therapies.

It’s a surprisingly simple process. A single user loads serum or other precious sample such as CSF onto a consumable chip. The next step is to insert that chip into the IsoLight/IsoSpark, and then walk away while the system performs all of the ELISA steps automatically. The user will return to fully analyzed quantitative data—no time is wasted on trying to parse out the data, allowing users more time to work on other important lab tasks.

Day 3: Single-cell secreted proteomics

Once researchers have narrowed down the drug candidates from Day 1, it’s time to drill down on the functional mechanisms at the single-cell level. Single-cell secreted proteomics allows the researchers to gain deeper insights into the immune response by profiling secreted proteins at single-cell resolution and obtain functional metrics that reveal insights into durability, persistence, and anti-tumor response, or toxicity and other immune-related adverse events. 

To gain these insights, the user can return to the samples previously collected for the low volume highly multiplexed proteomics and prepare a single-cell suspension to load a low volume of the sample of interest onto the single-cell chip. Once the chip is inserted into the IsoLight/IsoSpark system, the user can walk away while the system takes care of the rest.

Once again, the user returns to fully analyzed data. For each single cell that it captures, the system will profile up to 32+ different cytokines, translating to tens of thousands of data points, revealing the true function of each single cell. With the integrated IsoSpeak data informatics software, insights are delivered automatically with easy-to-read, advanced visualizations, simplifying complex analyses with an intuitive push-button user interface.

Day 4: Single-cell phosphoproteomics

Next, it’s time to peer inside the cell with single-cell phosphoproteomics. The researchers can now reveal the final piece of the puzzle by learning how the signaling pathways within the tumor cells themselves are responding to, or resisting, the drug treatment. This last step is crucial to get a full picture of both how the leading drug candidate is stimulating the immune system, and how the tumor is responding to the drug at single-cell resolution. Crucially, single-cell pathway omics can potentially help researchers design better combination therapies to defeat hard-to-treat tumors.

Once again, the user simply prepares and loads their samples onto the chip, inserts that chip into the IsoLight/IsoSpark, walks away, and returns to fully analyzed data.

A simple workflow

Each of these applications—low volume highly multiplexed proteomics, single-cell secreted proteomics, and single-cell pathway omics—traditionally involves numerous instruments and manual workflow steps. But, when using the IsoLight/IsoSpark, the same instrument can run several different applications, all with simple workflows and minimal hands-on time. For the user, that workflow is a matter of simply loading samples onto a consumable chip that fits into the palm of your hand, loading that chip into the instrument, and walking away. The rest is fully automated.