From Research to Therapy
Flow cytometry is widely used, with many applications in both research and clinical labs. For pharma and biotech labs, the ability to quickly perform multi-parameter quantitative analysis on large numbers of heterogeneous cells makes flow cytometry an important tool with many uses across the drug discovery pipeline. Here we focus on the importance of flow cytometry analysis for driving drug development through target identification and validation, hit identification and validation, lead optimization, and efficacy and safety studies.
Target Identification & Validation
The process of identifying and validating a molecular target within a disease pathway for drug treatment can be costly and time-consuming. Automated high throughput screening techniques offer the ability to rapidly test thousands of potential targets in vitro, however, the cells must then be analyzed with equal speed to avoid a bottleneck in the workflow. The development of high-throughput flow cytometry (HTFC) platforms using microwell plates has revolutionized the early phases of drug discovery. Unlike traditional tube-based flow cytometer platforms that require samples to flow under pressure, HTFC systems employ a technology called plug flow cytometry, which allows for repeated sampling from an open vessel. Modern platforms use barcoded 96- or 384-well plates and can be easily integrated into larger robotic workflows. Additionally, HTFC can be applied using either suspended cells or adherent cells after simple preparation procedures.
Hit Identification & Validation
After one or more molecular targets have been selected, a variety of small molecule drug compounds must be tested to find which compounds “hit”, or best bind the target and modify its function in the desired manner. Cell-based screening assays using HTFC analysis allow researchers to screen multiple compounds against a number of druggable targets within the context of living cells . Drug discovery programs are increasingly using primary cell models for compound assay screening, as they provide a more accurate representation of the physiological environment the drug will encounter in vivo. For more information see our article on primary cells.
Lead Optimization
Once a hit has been identified and validated against the target, the drug must be optimized to achieve the desired outcome with high specificity. The ability to analyze heterogeneous cell populations at specific time points makes flow cytometry a useful tool for testing drug-cell interactions. For example, flow cytometry is used to monitor cell cycle progression, proliferation, and apoptosis in both healthy and tumor cells when testing cellular responses to potential cancer drugs. In another study comparing analysis methods for testing antimalarial drugs, flow cytometry was found to provide more critical information on parasite stage development than optical microscopy or hypoxanthine uptake.
Efficacy and Safety Studies
When a novel drug candidate is finally selected for clinical trials, it must undergo multiple rounds (phases) of efficacy and safety testing in both animal and human subjects. Flow cytometry can be used to analyze drugs’ effects on a wide variety of diseases and patient samples. Some examples include analyzing how immune cells are affected by drugs to treat multiple sclerosis, testing peripheral blood and bone marrow samples treated for hematological malignancies or other tumors, and toxicology studies in many different cell types. Flow cytometry is a critical tool used throughout the drug discovery and development pipeline. The advent of plate-based high throughput flow cytometry has allowed analysis to keep pace with automated cell-based screening techniques. Flow cytometry is now being applied in both pre-clinical and clinical drug testing programs to deliver vast amounts of time-specific data on novel drug-cell interactions.
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