US researchers have developed a high-throughput microfluidic array to aid help discover therapeutic and cell-targeting peptide agents by measuring the interactions between cells and peptides.
The researchers from the University of Michigan, US developed the array to allow them to study the binding of synthetic peptides to cancer cells in the hope of developing new therapeutic and drug-targeting agents.
The new device, described in an early view article in the journal Biotechnology Progress allows researchers to manufacture peptides in situ before seeing which sequences are the most effective in binding the cells of interest.
"Creating a microfluidic platform for high-throughput cell - peptide interaction studies was inspired by the potential of cancer targeting peptides and the need for model substrates in cell-based biosensors," write the authors.
Combinatorial peptide chemistry has emerged as a powerful tool for mapping receptor-ligand interactions in drug discovery applications. However, according to the authors the identification of synthetic peptides that target tumour cells has been relatively unexplored.
By using a laser to remove photolabile protecting groups from small, defined areas within the device different peptide sequences can be synthesised at different locations to build up a peptide array.
This array can then be used to trap fluorescently labelled cells from a cell culture, such as the murine B cell lymphoma cell line WEHI-231 used by the researchers.
After un-trapped cells were washed away the array was then scanned using the Genepix 4000b microarray scanner from Molecular Devices (now part of MDS Instruments ).
Because the Genepix 400b has a resolution of 5um, smaller than that of the 8um lymphoma cells, the researchers were able to count the number of cells attached to each sequence area on the chip.
The study identified that the residues tryptophan (W), tyrosine (Y) and aspartic acid (D) are necessary residues for binding with the sequence. The ssequence WVDAV was found to be the most effective sequence studied for binding the murine lymphoma cells.
"We have created a flexible and cost-effective microfluidic platform for the application of synthetic peptide microarrays to the identification of sequence-specific cell binding ligands," write the authors.