A research team led by Associate Professor Johann Riemensberger from the Department of Electronic Systems at the Norwegian University of Science and Technology (NTNU) has developed a new kind of laser designed to overcome several challenges found in existing models.

"Our results can give us a new type of laser that is both fast, relatively cheap, powerful and easy to use," says Riemensberger.

The team's findings have been published in Nature Photonics. The project is a collaboration between NTNU, the Swiss École Polytechnique Fédérale de Lausanne (EPFL), and Luxtelligence SA.

Self-driving cars and air quality detectors

Traditional precision lasers are often bulky, costly, and tricky to fine-tune.

"Our new laser solves several of these problems," says Riemensberger.

This improvement could make the technology especially useful in self-driving cars, which rely on a technique known as Lidar to map their surroundings. Lidar works by measuring how long it takes light from a laser to bounce back, or by detecting tiny changes in the light's wave phase. The new laser can perform such measurements with remarkable accuracy -- within about four centimeters.

The researchers also demonstrated that their laser can effectively detect hydrogen cyanide gas in the air, a substance commonly referred to as "hydrocyanic acid." Because this compound is extremely toxic even in small amounts, being able to identify it quickly is essential for safety and environmental monitoring.

Advanced materials, microsized light circuits

The researchers created the new laser with advanced materials and microscopic light circuits.

The laser emits a powerful and stable beam of light. Also, among the advantages is that users can easily adjust the frequency quickly and smoothly, without sudden jumps.

"You can also easily control it with just one control instead of many," Riemensberger points out.

The laser is built using chip technology that is already available. This makes it possible to mass-produce it cheaply.

"Our findings make it possible to create small, inexpensive and user-friendly measuring instruments and communication tools with high performance," Riemensberger said.

The work was a collaboration between EPFL (experiments), Luxtelligence SA (chip production) and NTNU (design and simulations). It started when Riemensberger was still a postdoctoral fellow at EPFL. The collaboration continues through an EIC Pathfinder OPEN scholarship called ELLIPTIC.

A team of EMBL researchers and collaborators has now created a tool that takes single-cell analysis to a new level. It can capture both genomic variations and RNA within the same cell, offering greater accuracy and scalability than earlier technologies. This approach allows scientists to identify variations in non-coding regions of DNA, the areas most often linked to disease, giving them a new way to explore how genetic differences contribute to human health. With its precision and ability to process large numbers of cells, the tool marks a major step toward linking specific genetic variants with disease outcomes.

"This has been a long-standing problem, as current single-cell methods to study DNA and RNA in the same cell have had limited throughput, lacked sensitivity, and are complicated," said Dominik Lindenhofer, the lead author on a new paper about SDR-Seq published in Nature Methods and a postdoctoral fellow in EMBL's Steinmetz Group. "On a single-cell level, you could read out variants in thousands of cells, but only if they had been expressed -- so only from coded regions. Our tool works, irrespective of where variants are located, yielding single-cell numbers that enable analysis of complex samples."

The important difference between coding and non-coding regions

DNA contains both coding and non-coding regions. The coding parts function like instruction manuals, since their genes are expressed into RNA, which directs cells in building proteins essential to life.

Non-coding regions, on the other hand, contain regulatory elements that guide how cells grow and function. Over 95% of disease-linked DNA variants occur in these non-coding regions, yet existing single-cell methods have not had the sensitivity or scale to study them effectively. Until now, researchers were unable to observe DNA and RNA from the same cell on a large scale, limiting insight into how DNA variants affect gene activity and contribute to disease.

"In this non-coding space, we know there are variants related to things like congenital heart disease, autism, and schizophrenia that are vastly unexplored, but these are certainly not the only diseases like this," Lindenhofer said. "We needed a tool to do that exploration to understand which variants are functional in their endogenous genomic context and understand how they contribute to disease progression."

Deciphering barcodes that track single cells

To perform single-cell DNA-RNA sequencing (SDR-seq), researchers used tiny oil-water droplets, each containing a single cell, allowing them to analyze DNA and RNA simultaneously. This method enabled them to examine thousands of cells in a single experiment and directly link genetic changes to patterns of gene activity. Developing this technology required overcoming major challenges and brought together teams from EMBL's Genome Biology and Structural and Computational Biology units, the Stanford University School of Medicine, and Heidelberg University Hospital.

Collaborators from EMBL's Judith Zaugg and Kyung-Min Noh groups developed a way to preserve delicate RNA by "fixing" the cells, while computational biologists in Oliver Stegle's group designed a specialized program to decode the complex DNA barcoding system needed for data analysis. Although this decoding software was built for this specific project, the team believes it could prove valuable for many other studies.

Researchers from Wolfgang Huber's and Sasha Dietrich's groups at EMBL and Universitätsklinikum Heidelberg were already examining B-cell lymphoma samples for other studies. These patient samples, rich in genetic variation, provided an ideal test case for the new technology. Using these samples, Lindenhofer observed how variations in DNA were linked to disease processes and found that cancer cells with more variants showed stronger activation signals that support tumor growth.

"We are using these small reaction chambers to read out DNA and RNA in the same single cell," Lindenhofer said. "This lets us accurately tell whether a variant is on one or both copies of a gene and measure its effects on gene expression in the same single cells. With the B-cell lymphoma cells, we were able to show that depending on the variant makeup of cells, they had different propensities to belong to distinct cellular states. We could also see that increasing variants in a cell actually were associated with a more malignant B-cell lymphoma state."

The many opportunities from a single-cell sequencing tool

The SDR-seq tool now offers genomic biologists scale, precision, and speed to help better understand genetic variants. While it could eventually play a role in treating a broad range of complex diseases, it may first help in developing better screening tools for diagnosis.

"We have a tool that can link variants to disease," said Lars Steinmetz, a senior author on the paper, an EMBL group leader, and a genetics professor at Stanford University School of Medicine. "This capability opens up a wide range of biology that we can now discover. If we can discern how variants actually regulate disease and understand that disease process better, it means we have a better opportunity to intervene and treat it."