Cell surface sensors could advance precision medicine

1 October 2019:

Researchers have found a way to identify multiple cell signalling proteins using a single cell rather than the billions of cells used previously.

The new measurement technology, developed by researchers at the ARC Centre of Excellence for Nanoscale Biophotonics, brings precision medicine a step closer.

“Cells secrete various messenger molecules, such as cytokines. They may indicate the presence of a disease or act as a driver of key therapeutic effects,” says Dr Guozhen Liu, lead author of paper detailing the technology.

The method, termed OnCELISA, uses antibodies attached on specially engineered cell surfaces to capture cytokine molecules before they have a chance to disperse away from the cell.

The secreted messenger proteins such as cytokines are reported, at the single cell level, by using fluorescent magnetic nanoparticles.

Cytokines secreted from cells play a critical role in controlling many physiological functions, including immunity, inflammation, response to cancer, and tissue repair.

 

The image represents our sensor during the process of detecting cytokine molecules being secreted from cells. The sensor is represented by a pair of Y-shaped antibodies, the capture antibody (purple stem) and the detection antibody (pink stem).

The OnCELISA system can be used for ultrasensitive monitoring of cytokine release by individual cells, and it can also help discover cell populations with therapeutic value.

“The ability to identify and select cell populations based on their cytokine release is particularly valuable in commercial cell technologies and it can help develop unique products, such as future non-opioid pain relief” says Dr Liu.

“Importantly, our design uses commercially available reagents only, so it can be easily reproduced by others,” she adds.

While the published work focuses on specific proinflammatory cytokines IL-6 and IL-1β, the method is potentially suitable for a broad range of other secreted proteins and cell types.

The new technique represents an advance on traditional methods such as the enzyme-linked immunosorbent assays (ELISA) that detect average levels of secreted molecules from cell ensembles.

The OnCELISA takes the ELISA approach to its absolute extreme, by detecting cytokines on the surface of individual, single live cells.

The publication has been reported by prestigious iScience journal and can be found at https://www.sciencedirect.com/science/article/pii/S2589004219303578.

Journal: iScience

Publication Title: A Nanoparticle-Based Affinity Sensor that Identifies and Selects Highly Cytokine-Secreting Cells

Authors: Guozhen Liu; Christina Bursill; Siân P.Cartland; Ayad G.Anwer; Lindsay M.Parker; Kaixin Zhang; Shilun Feng; Meng He; David W.Inglis; Mary M.Kavurma; Mark R.Hutchinson; Ewa M.Goldys

Summary: We developed a universal method termed OnCELISA to detect cytokine secretion from individual cells by applying a capture technology on the cell membrane. OnCELISA uses fluorescent magnetic nanoparticles as assay reporters that enable detection on a single-cell level in microscopy and flow cytometry and fluorimetry in cell ensembles. This system is flexible and can be modified to detect different cytokines from a broad range of cytokine-secreting cells. Using OnCELISA we have been able to select and sort highly cytokine-secreting cells and identify cytokine-secreting expression profiles of different cell populations in vitro and ex vivo. We show that this system can be used for ultrasensitive monitoring of cytokines in the complex biological environment of atherosclerosis that contains multiple cell types. The ability to identify and select cell populations based on their cytokine expression characteristics is valuable in a host of applications that require the monitoring of disease progression.

Link: https://doi.org/10.1016/j.isci.2019.09.019