6/10/2025 Ben Libman
Researchers in Andrew Smith’s, including postdoc Yujun Feng, lab have developed “nanocoding,” a new way to tag cells using lipid nanoparticles that deliver DNA barcodes directly into cells, overcoming issues like uneven labeling or toxicity seen with traditional methods. By treating cells with simple chemical linkers, every cell gets a stable, non-toxic label that won’t fall off or swap, enabling mixed-sample experiments under identical conditions. This accessible technique, requiring only commercially available reagents and minimal training, could accelerate research into diseases such as cancer, obesity, and aging by making single-cell studies faster, cheaper, and more reliable.
Written by Ben Libman
In any biological experiment, cell labeling is crucial. For example, picture a researcher performing an experiment on cells from two different mice- one obese, and one at its ideal body weight. Ideally, the cells would be mixed together before performing the experiment- this ensures each cell experiences identical conditions. But how will the researcher be able to tell which cells came from which sample when tabulating the results? This can be accomplished by “barcording”- attaching a unique barcode to each cell, not unlike those you would find in a grocery store. These codes are attached to cells prior to mixing them together, which allow the researchers to determine where they came from. But traditional barcoding methods have limitations. The barcodes may not attach to certain cells, especially in complex tissues. Cells may be damaged due to toxic effects. Barcodes can even fall off or swap between cells, leading to confusing or misleading results.
Researchers in professor Andrew Smith’s lab, led by postdoc Yujun Feng, have developed a new method of barcoding that alleviates these issues. Their method, recently published in ACS Nano, is called “Nanocoding.” Nanocoding works by using lipid nanoparticles (LNPs) to encapsulate and deliver DNA barcodes into cells directly. The cells are treated beforehand with chemical linkers to help bind the LNPs, ensuring every cell is labeled. The resulting bond is strong and won’t easily fall off the cell. The lipids are nontoxic, meaning the cells won’t be damaged.
This also enables researchers to ensure that rare cells are labeled. “The biggest questions that can be answered [by nanocoding] are related to cells extracted from solid tissues like adipose tissue and the brain, which contain cells that are structurally diverse and therefore may not be labeled evenly by barcodes,” said professor Smith. “Questions regarding the cell types involved in disease processes can now be addressed, especially the ways in which immune cells change throughout the development of inflammatory diseases such as obesity and in the process of aging.”
To demonstrate the power of their new technique, Smith and Feng ran two experiments on mice. They compared spleen cells from obese and lean mice, as well as visceral fat tissues from young and old mice. The cells were labeled by nanocoding and then mixed together, ensuring the exact same experimental and assessment conditions between the samples. Afterwards, nanocoding allowed the results to be measured in each individual cell. The researchers were able to discover differences between the two, providing insights into the health effects of obesity and aging. T cells in the aged mice showed signs of exhaustion- a biological state where cells are overactivated and lose their function. They also were able to identify fewer macrophages in the aged tissue, suggesting age-related slowdown in production or infiltration into the tissue. Similarly, the researchers were able to identify more inflammatory genes expressed in obese mice than lean mice. This mirrors findings in humans, demonstrating nanocoding’s ability to detect disease-related effects.
This method holds strong potential for clinical use. “Nanocoding could allow easy analysis of multiple sequential samples of blood from patients and evaluation of numerous regions of a tumor or multiple biopsies,” said Smith. “For cancer diagnostics, specifically, this would provide an evaluation of tumor heterogeneity while minimizing cost and allowing quantitative comparisons across these samples.” Smith also says the method is extremely accessible for other researchers. “No proficiency in chemistry or molecular biology is needed. All of the reagents are commercially available and can be performed with minimal training and without the need for unique equipment. Other current approaches require proprietary chemicals. Further, it is easy to develop the nanocoding approaches for new types of unique samples due to a plethora of lipids available commercially.”
The team’s work is not over. Next, the lab hopes to increase the stabilization of the materials needed for nanocoding. Still, the future for nanocoding is bright. By allowing scientists to batch and barcode cells from different sources, nanocoding makes single-cell experiments faster, more affordable, and more accurate, accelerating discoveries in diseases like cancer, obesity, and aging. It’s another way the Department of Bioengineering at The Grainger College of Engineering, University of Illinois Urbana-Champaign is shaping the future.
The full article is available here.
Andrew Smith is a Donald Biggar Willett Faculty Fellow. He is a professor of Bioengineering, Medicine, and Technology Entrepreneurship at The Grainger College of Engineering, University of Illinois Urbana-Champaign and Carle Illinois College of Medicine. He is a Research Theme Faculty at the Center for Genomic Diagnostics (CGD) and Carl R. Woese Institute for Genomic Biology. He is also a Resident Faculty at the Holonyak Micro and Nanotechnology Laboratory (HMNTL). Smith is an Affiliate Faculty in the Department of Materials Science and Engineering.