BellBrook Labs Launches New Microplate for High Content Chemotaxis Assays in a Stable Gradient

BellBrook Labs announces that it has completed successful field testing on their iuvo Chemotaxis Assay Plate and is transitioning the product to a full commercial launch. The plates provide drug discovery researchers with high quality data on the potency of compounds that affect neutrophil chemotaxis, a key goal for intervening in inflammatory diseases and disorders.

Instead of wells, the new plates have precisely engineered microconduits formatted in the familiar 96-point array, each with two ports positioned for standard liquid dispensing equipment. This design allows delivery of cells at the trailing edge of a concentration gradient of chemoattractant, which forms spontaneously and is sustained for several hours. The progress of neutrophils migrating horizontally into the gradient region can be monitored with common microscopic imaging instrumentation used for high content analysis. Improvements over existing methods include cell migration in a defined, stable gradient of chemoattractant, a completely automated assay format, and a 10-fold reduction in cell usage.

Neutrophil chemotaxis from the bloodstream to sites of infected or damaged tissue is one of the fundamental processes underlying inflammation. It is driven by the directional migration of cells up a concentration gradient of signaling molecules secreted by cells at the site of inflammation. The inhibition of this process is one of the main avenues for discovery of new treatments for a range of inflammatory disorders, including arthritis and chronic obstructive pulomonary disorder (COPD). However, the methods used to screen and rank potential drug molecules for their affects on neutrophil chemotaxis are relatively crude. In the most widely used approach, multiwell plate inserts with porous membranes are used to partition cells and chemoattractant into separate compartments. Chemotaxis is measured by counting the cells that pass through the membrane toward the chemoattractant in the outer compartment. A fundamental shortcoming of this approach is that the chemoattractant gradient – the key driver of chemotaxis- varies with experimental conditions such as cell density. This and sticking of cells to the membrane contribute to a high level of data variability. In addition, adding and removing the membrane inserts disrupts workflow in an automated HTS environment, as it generally requires manual intervention.

In the iuvo Chemotaxis Assay Plate, the simple “bucket” geometry of the well is replaced with a microconduit that is specifically designed to generate a defined and stable gradient of chemoattractant, to deliver cells at the trailing edge of that gradient, and to allow microscopic imaging of cells migrating up the gradient. Chemoattractant, cells and test compound can be dispensed into the ports using automated liquid dispensing equipment, with no manual intervention. The microscale dimensions of the microconduits means that far fewer cells are required than with current methods, an important advance for an assay that relies on primary cells. Microscopic imaging at low power magnification is used to determine the number of cells migrating and distance traveled, as well as changes in cell morphology that can give clues to the mechanism of chemotaxis effectors.