CSEM has supported Lausanne-based startup Alithea Genomics in developing a technology capable of processing hundreds of RNA samples in a single tube, translating into a significant reduction in reagents and manual effort in the general workflow.
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 read-out of gene expression. RNA-seq can help us understand the biology of organisms. However, despite the potential of the method, at present there is a lack of large-scale and cost-effective sample preparation for RNA-seq, which has so far prevented widespread adoption of this method by industry professionals.
BRB-seq technology helps advance our understanding of biological processes
To overcome the high cost of routine sample preparation for RNA-seq processes, the Systems Biology and Genetics Laboratory at EPFL and its spin-off company Alithea Genomics developed the “Bulk RNA Barcoding and Sequence” (BRB-seq) technology. The researchers analyze the cells’ gene expression, which can help them understand how the cells function and respond to various conditions. The method relies on early-stage molecular coding to distinguish different samples, enabling them to be processed together for RNA-sequencing in bulk. 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
Under the Bridge and Innosuisse projects, Alithea Genomics and CSEM’s Tools for Life Sciences team developed technology to automate the collection of all samples from multiwell 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 various standard microwell plate formats. Connected by a pump in a self-contained platform, the casing can transfer fluids from wells by vacuum extraction into a single tube. This allows potential treatment of hundreds to thousands of wells at once. The final design can collect more than 90% of the contents of up to four 96-well dishes in less than two minutes.
With its compact nature and great potential for upgradability, this simple yet effective system is ideally suited to research laboratories working in limited physical space. The medium throughput system is based on disposable laboratory software and has been tested under stack conditions, which increases 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 processing with improved time efficiency.
“The easy-to-use barcoder kit and simple collection of all samples significantly reduces the cost of per-sample RNA sequencing. We expect these technologies to reach their intended market within the next five years, enabling RNA big data processing for drug discovery.” , confirms Stephanie Bouder-Bashi, Senior Project Manager at CSEM.
Making biobank analysis and drug screening efforts more efficient
“The market need for assembly technology will be driven by the adoption of BRB-seq technology by major pharmaceutical and R&D companies,” explains Dr. Ricardo Diñez, CEO of Alithea Genomics. “Our patented BRB-seq method significantly lowers expenses while increasing throughput of RNA-seq. The technology allows tasks previously impossible to be performed due to cost and labor constraints.”
Applications from single-cell analysis to diagnostics
Evaluation of gene activity in biological samples, such as transcriptome analysis, gene expression profiling, identification of novel transcripts, and mutations in cancer research, among others, holds great potential for discovery and development of new drugs and diagnostics.
This collaboration has enabled us to serve the high-throughput field of genomics and push our Smart Lid technology even further. The variety of smart covering formats and functionality is promoting them as enabling technologies for the life sciences industry. This knowledge, combined with our expertise in AI for life sciences and biosystems engineering in the Basel Switzerland innovation region of Alschuelle, allows us to offer multidisciplinary solutions for life sciences applications.”
Jill Wedder, Co-President of Research and Business Development for Life Sciences Technologies, CSEM.