Lab on Chip for testing Myelotoxic effect of Drugs and chemicals


People involved: Alberto Redaelli, Marco Rasponi, Gianfranco B. Fiore, Paola Occhetta, Andrea Gazaneo

Funding source: Cariplo Foundation (grant no. 2011-0322)

Funding period: 2012 - 2014

Partners: Facoltà di Medicina e Chirurgia - Università Statale di Milano.

In 2006 the European Centre for the Validation of Alternative Methods (EVCAM) has approved the Colony Forming Unit-Granulocytes-Macrophages (CFU-GM) assay, which is the first and currently unique test applied to evaluate the hematotoxicity of xenobiotics in vitro.

The CFU-GM assay is a clonogenic test based on the study in vitro of the acute effect of toxicants on bone marrow progenitors under maximally stimulatory cytokine concentrations. Briefly, it consists in seeding bone marrow progenitors in a methylcellulose semi-solid medium (to avoid cell spreading), subsequently delivering known drug concentrations, and finally quantifying the colonies of cells formed by the surviving progenitors. Based on the percentage of cells which are still able to demonstrate clonogenic activity after toxicant exposure, it is thus possible to identify the maximum tolerated dose of drugs.

Although the CFU-GM assay has several advantages (and enormous ethical benefits) over the traditional in vivo tests on animal models, the sequence of manual operations is time consuming, and the required amounts of precious progenitor cells and costly drugs limit its spreading.

Goal of the LoCMeD project is to realize a digital microfluidic system that enables trapping, feeding and growing of multipotent monoclonal stem cells. Thanks to the microfluidic Large Scale Integration (µLSI) technology, we plan to develop a microfluidics platform hosting directly onboard a complex control system, made of valves, pumps and mixers, and that will be multiplexed to individually control thousands bioreactor chambers each containing a predetermined number of cells. Finally, the for cell culturing, drug dosing and delivering, and colony counting will be automated by programming the protocol procedures on the embedded control system.