Breakthrough medical technology like mRNA vaccines rely on tiny nanoparticles to deliver medicine to cells. A new device will help drug manufacturers and evaluators like the FDA more precisely measure genetic payloads to evaluate drug effectiveness.
An important component of the vaccines protecting people against SARS-CoV-2 virus and its variants are lipid nanoparticles, or LNPs. These circular particles carry therapeutic mRNA payloads, the snippets of genetic material that trigger our immune systems to defend against COVID-19. Even with their success, certain characteristics about the particles, such as payload distribution, are unknown. Researchers and the Food and Drug Administration want more insights about these characteristics to improve metrics reporting in pharmaceutical manufacturing.
A new molecular detection platform developed by two Whiting School of Engineering professors is answering the FDA’s call. Hai-Quan Mao and Tza-Huei (Jeff) Wang want to address how many mRNA molecules an LNP can carry and whether the mRNA is uniformly packed inside the particle to help researchers design more efficient and effective treatments and vaccines.
“Our platform processes molecules at the single nanoparticle level, but unlike the current imaging methods for mRNA LNPs, our approach is based on fluorescent spectroscopy and gives us the ability to see through the particles,” said Wang, a professor in the departments of Mechanical Engineering and Biomedical Engineering at the Whiting School, and a core researcher at the Institute for NanoBioTechnology.
The ability to peer inside the nanoparticles allows the researchers to differentiate between and measure empty LNPs that do not contain mRNA, LNPs with mRNA, and free-floating mRNA in a sample.
Their platform, called cylindrical illumination confocal spectroscopy, or CICS, works by tagging mRNA and LNP components with fluorescent signals of up to three colors and passing the sample through a detection plane. The detection plane reads the fluorescent signals and measures their intensity before comparing the strength of the intensities with that of a single mRNA molecule. The data analysis with an algorithm called deconvolution tells the team both how many mRNA copies are inside the LNP—if any—and their distribution in the sample. The team’s platform overcomes contrast limitations and increases the sample analysis throughput, that are seen in cryo-transmission electron microscopy, the current gold standard for imaging mRNA LNPs.
Tests conducted using this sensing platform revealed that from a benchmark solution of mRNA LNP used in academic research studies, over 50% of the LNPs are not loaded with mRNA molecules, and of the mRNA-filled LNPs, most of them contained two to three mRNA molecules per particle.
“Being able to quantitatively resolve payload characteristics of mRNA LNPs at the single particle level has never been done before. We are intrigued by the substantial presence of empty LNPs, and by altering formulation conditions, a single nanoparticle can load as few as one to as many as ten mRNA molecules.” said Mao, professor in the departments of Materials Science and Engineering and Biomedical Engineering at the Whiting School and director of the Institute for NanoBioTechnology.
The team’s results are published in Nature Communications.
“There are a lot of groups doing LNP research,” Wang said. “However, when they discover a formula that might work well, it has been hard to associate those discoveries back to the composition and payload distribution of the nanoparticles. With this platform we can provide a more comprehensive understanding on what is happening at the single particle level.”
More research is needed to learn how many mRNA molecules per LNP capsule is optimal for the most effective treatment. However, the empty LNPs revealed by the new platform show there is a need to improve methods for packaging the mRNA inside the LNPs.
Mao and Wang say that their platform shows that it has the potential to not only be used at all stages of LNP-related research and development, but also in the development of other drug delivery systems and quality control measures at the manufacturing stage. The team has filed a patent application covering the technique and is working with collaborators to use the platform to analyze other types of therapeutic cargos in diverse nanoparticle systems for treating different diseases.
“The FDA has recently addressed the need for better quality metrics in nanoparticle design in the pharmaceutical industry,” said Michael J. Mitchell, a leading scientist in the field of LNP research and Skirkanich Assistant Professor of Innovation in the Department of Bioengineering at the University of Pennsylvania. “This will become increasingly more important as mRNA LNP technology expands beyond vaccines into new therapeutics that are administered into the bloodstream, which have very stringent requirements. The new detection platform developed by Drs. Mao and Wang’s team is a potentially important step forward in addressing needs at the research and regulatory phase, and can potentially aid in the development of mRNA LNP technology beyond vaccines.”
News
AI therapy may help with mental health, but innovation should never outpace ethics
Mental health services around the world are stretched thinner than ever. Long wait times, barriers to accessing care and rising rates of depression and anxiety have made it harder for people to get timely help. As a result, governments and health care providers are [...]
Global life expectancy plunges as WHO warns of deepening health crisis Post-COVID
The World Health Organization (WHO) has sounded the alarm on the long-term health repercussions of the COVID-19 pandemic in its newly released World Health Statistics Report 2025. The report reveals a staggering decline in global [...]
Researchers map brain networks involved in word retrieval
How are we able to recall a word we want to say? This basic ability, called word retrieval, is often compromised in patients with brain damage. Interestingly, many patients who can name words they [...]
Melting Ice Is Changing the Color of the Ocean – Scientists Are Alarmed
Melting sea ice changes not only how much light enters the ocean, but also its color, disrupting marine photosynthesis and altering Arctic ecosystems in subtle but profound ways. As global warming causes sea ice in the [...]
Your Washing Machine Might Be Helping Antibiotic-Resistant Bacteria Spread
A new study reveals that biofilms in washing machines may contain potential pathogens and antibiotic resistance genes, posing possible risks for laundering healthcare workers’ uniforms at home. Washing healthcare uniforms at home could be [...]
Scientists Discover Hidden Cause of Alzheimer’s Hiding in Plain Sight
Researchers found the PHGDH gene directly causes Alzheimer’s and discovered a drug-like molecule, NCT-503, that may help treat the disease early by targeting the gene’s hidden function. A recent study has revealed that a gene previously [...]
How Brain Cells Talk: Inside the Complex Language of the Human Mind
Introduction The human brain contains nearly 86 billion neurons, constantly exchanging messages like an immense social media network, but neurons do not work alone – glial cells, neurotransmitters, receptors, and other molecules form a vast [...]
Oxford study reveals how COVID-19 vaccines prevent severe illness
A landmark study by scientists at the University of Oxford, has unveiled crucial insights into the way that COVID-19 vaccines mitigate severe illness in those who have been vaccinated. Despite the global success of [...]
Annual blood test could detect cancer earlier and save lives
A single blood test, designed to pick up chemical signals indicative of the presence of many different types of cancer, could potentially thwart progression to advanced disease while the malignancy is still at an early [...]
How the FDA opens the door to risky chemicals in America’s food supply
Lining the shelves of American supermarkets are food products with chemicals linked to health concerns. To a great extent, the FDA allows food companies to determine for themselves whether their ingredients and additives are [...]
Superbug crisis could get worse, killing nearly 40 million people by 2050
The number of lives lost around the world due to infections that are resistant to the medications intended to treat them could increase nearly 70% by 2050, a new study projects, further showing the [...]
How Can Nanomaterials Be Programmed for Different Applications?
Nanomaterials are no longer just small—they are becoming smart. Across fields like medicine, electronics, energy, and materials science, researchers are now programming nanomaterials to behave in intentional, responsive ways. These advanced materials are designed [...]
Microplastics Are Invading Our Arteries, and It Could Be Increasing Your Risk of Stroke
Higher levels of micronanoplastics were found in carotid artery plaque, especially in people with stroke symptoms, suggesting a potential new risk factor. People with plaque buildup in the arteries of their neck have been [...]
Gene-editing therapy shows early success in fighting advanced gastrointestinal cancers
Researchers at the University of Minnesota have completed a first-in-human clinical trial testing a CRISPR/Cas9 gene-editing technique to help the immune system fight advanced gastrointestinal (GI) cancers. The results, recently published in The Lancet Oncology, show encouraging [...]
Engineered extracellular vesicles facilitate delivery of advanced medicines
Graphic abstract of the development of VEDIC and VFIC systems for high efficiency intracellular protein delivery in vitro and in vivo. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-59377-y. https://www.nature.com/articles/s41467-025-59377-y Researchers at Karolinska Institutet have developed a technique [...]
Brain-computer interface allows paralyzed users to customize their sense of touch
University of Pittsburgh School of Medicine scientists are one step closer to developing a brain-computer interface, or BCI, that allows people with tetraplegia to restore their lost sense of touch. While exploring a digitally [...]
