Over the past decade, RNA sequencing (RNA-seq)* has become increasingly popular in genomics and therapeutic drug testing. RNA-seq examines gene expression in the entire genome, providing a complete and unbiased gene expression readout. RNA-seq can help us understand the biology of living things. However, despite the method’s potential, at present there is a lack of large-scale and cost-efficient sample preparation for RNA-seq, which has so far prevented this method’s widespread adoption by industry professionals.
BRB-seq technology helps advance our understanding of biological processes
To overcome the high expense of routine sample preparation for RNA-seq operations, the Laboratory of Systems Biology and Genetics at EPFL and its spin-off company Alithea Genomics have developed "Bulk RNA Barcoding and sequencing” (BRB-seq) technology. It allows researchers to analyze the gene expression of cells, which can help them understand how cells function and respond to different conditions. The method relies on early-stage molecular barcoding to tag the different samples, enabling them to be processed together for bulk sequencing RNA. Aiming at medium to high-throughput, samples are processed in 96 or 384 multi-well plates before being collected into a single tube.
Simple and effective systems based on CSEM’s Smart Lid platform
In the framework of Bridge and Innosuisse projects, Alithea Genomics and CSEM’s Tools for Life Sciences team developed a technology to automate the collection of all samples from the multi-well plates into a single tube. Their solution, called Microfluidic Pooling Lid, is based on CSEM’s Smart Lid platform, which integrates microfluidic channels and can accommodate different, standard micro well plate formats. Connected by a pump in a standalone platform, the lid can transfer the liquids from the wells via vacuum extraction into a single tube. This allows the potential processing of hundreds to thousands of wells in one go. The final design can pool over 90% of the contents of up to four 96-well plates in under two minutes.
Thanks to its compact nature and great potential for upscaling, this simple but effective system is ideally suited for research laboratories operating in a limited physical space. The medium-throughput system relies on disposable labware and was tested in stacked conditions, increasing the amount of RNA that can be processed with the same time and footprint. Validated by EPFL for RNA-seq sample processing, it shows the same performance as manual handling while improving time efficiency.
“The easy-to-use barcoding kit and simple pooling of all samples significantly reduce RNA sequencing cost per sample. We anticipate that these technologies will reach the intended market within the next five years, enabling big data RNA processing for drug discovery,” underlines Stéphanie Boder-Pasche, Senior Project Manager at CSEM.
Making biobank analysis and drug screening efforts more efficient
“The market need for pooling technology will be driven by the adoption of the BRB-seq technology by big pharma and R&D players,” explains Dr. Riccardo Dainese, CEO of Alithea Genomics. “Our BRB-seq patented method significantly lowers expenses while boosting RNA-seq throughput. The technology allows to perform tasks that were previously impossible due to cost and labor constraints.”
Applications from single-cell analysis to diagnostics
The assessment of gene activity in biological samples, such as transcriptome analysis, gene expression profiling, novel transcript identification, and mutations in cancer research, among others, holds significant potential for the discovery and development of novel drugs and diagnostics. “This collaboration has enabled us to serve the field of high-throughput genomics and push our Smart Lid technology further. The variety of smart lids formats and functions is promoting them as enabling technologies for the life sciences industry,” surmises Gilles Weder, Co-Head Research & Business Development Life Science Technologies at CSEM. “This know-how, combined with our expertise in AI for life sciences and biosystems engineering in the Switzerland Innovation Park Basel Area in Allschwil, allows us to provide interdisciplinary solutions for life sciences applications.”
*Note: While DNA sequencing studies genetic inheritance (genomics), RNA sequencing studies how our genes are expressed in our cells (transcriptomics). Genes are like instructions for our body, which are transmitted by RNA. By analyzing the RNA profile of a cell, it is possible to detect which genes are active. This information can be used to better understand diseases and develop new treatments.