Alex Okun

Flow cytometry systems for drug discovery and development

HT-PS is a fluidics-based pharmacology platform that uses viable cells and test compounds to rapidly identify active compounds and immediately determine their potency and specificity. Axiom employs this proprietary flow-through fluidics system coupled to a flow cytometer (FCM) as a detection system. Integration of FCM was enabled through a Plug-Flow Coupler (PFC) device that allows mixtures of cells and test compounds to be delivered to the FCM as discrete plugs of samples under positive air pressure. An FCM detector provides the advantages of multi parametric measurements and multiplexed, single cell analyses. Assays that combine two or more compatible, fluorescent bioresponse indicators simultaneously, such as measurements of intracellular pH and Ca2+, are possible. Alternatively, measurements of one or more bioresponses can be performed on several distinct cell populations individually stained with uniquely addressable fluorescent chromophores. These formats enable multiple experiments on a single sample and provide high content information thereby greatly increasing decision-making power regarding the activity, potency and selectivity of a test compound. Development of significant data with several hundred cells enables reduction in all requisite sample volumes. The PFC enables FCM sample analysis rates of at least 10 samples/minute. The data will illustrate HT-PS/PFC/FCM utility in the drug discovery arena.

High-throughput pharmocology system HT-PS 100: instrument for automated quantitative analysis of a ligand-receptor interaction based on ligand concentration-dependent functional responses in cells

Contrary to conventionally used serial discrete dilutions of a ligand to construct concentration-response curves with a few experimental points, we describe here an automated system, HT-PSTM 100, that produces continuous ligand concentration gradients for interrogating cells in flow, and concurrently measures the ligand-induced functional response.