April 2018

NML one of first laboratories to receive delivery of BD Rhapsody single cell analysis instrument

The Molecular & Cell Biology team within the National Measurement Laboratory (NML) at LGC recently had one of the first BD Rhapsody single cell analysis instruments in the world installed.

This state-of-the-art technology, which combines single-cell capture with molecular indexing, forms part of the development of a unique novel measurement facility within the NML, funded through our Industrial Strategy Challenge Fund (ISCF) project ‘Measurement for Future Medicines’.

As well as RNA expression profiling using the Rhapsody system, single cell measurements of other markers including DNA and proteins are supported through our new cell sorting and improved flow cytometry capabilities. Furthermore, this facility will enable high throughput analyses of the proteins present in single cells through a combination of antibody labelling techniques and high speed bio-imaging mass spectrometry (laser ablation coupled to ICP ToF MS) at sub-micron resolution.

Novel manufacturing methods rely on being able to measure and characterise the medicines accurately, both in their place of manufacture and in our bodies. Many biological experiments are performed on groups of cells, under the assumption that all cells of a particular ‘type’ are similar. However, studies of single cells reveal that individual cells within the same population may differ from each other and in their response to stimuli, having consequences for the efficacy of cell-based treatments. Greater understanding of real cellular variance and how it contributes to mean response using new techniques and technologies opens up analyses not otherwise possible.

This new instrument will enable high throughput isolation of single cells and characterisation of their gene expression using next generation sequencing (NGS). Approximately 10,000 individual cells can be analysed in a single experiment, compared to previous technology which is limited to 100s of cells. This enables better sensitivity for the detection of rare cell types which may be detrimental to therapeutic treatment. Establishing robust tools for quantifying cellular heterogeneity will lead to greater confidence in the safety of future medicines.

As Alison Devonshire, Science Leader, Nucleic Acid Metrology, noted, "This new technology will allow us to further develop our single cell analysis capabilities to support our activities within engineering biology and precision medicine, for example for stem cell based therapies or understanding the heterogeneity of cancer cells.”

The placement of the Rhapsody system in a national measurement laboratory supports application of this single cell technology in commercial applications as commented on by Dr. Nikhil Rao, Global Product Manager, Rhapsody Products (BD Life Sciences), “We are excited to have the opportunity to work with the National Measurement Laboratory at LGC.  We believe that LGC’s work to evaluate targeted single-cell RNA Seq data for reproducibility and standardization will be extremely valuable for the commercial community to further our confidence in scientific discoveries and validation studies in healthcare.  The combination of our BD Rhapsody Single-Cell Analysis System and the BD Sample Multiplex Kit for labelling cells in different samples (“cell hashing”) will enable the natural movement of researchers from discovery using whole transcriptome approaches to more statistically relevant, higher confidence NGS findings and translate these to impactful biological insights”.

If you would like to find out more about the ISCF project or are interested in working with us in this area, please email us.