Jeonbuk National University (JBNU) Department of Physics research team led by Professor Sangmin Ahn, in collaboration with Professor Jongchul Han of Samsung Medical Center, Professor Manhee Lee of Chungbuk National University, and Professor Wonho Je of Seoul National University, has developed an innovative analytical technique that can simultaneously measure mass, density, and solute concentration from a single ultramicrodroplet of liquid of approximately 1 nanoliter (nL), a scale comparable to the thickness of a human hair.

The researchers applied the developed technique to human aqueous humor and, for the first time in the world, demonstrated that the density and total dissolved solids (TDS) concentration of aqueous humor vary between individuals. Aqueous humor is the transparent fluid that fills the interior of the eye. Because only very small volumes can be collected, accurate quantification was nearly impossible with conventional analytical methods.

In measuring the mass of ultralow-volume liquids using a quartz tuning fork, the team utilized ultrahigh-frequency longitudinal waves formed inside the droplet. Existing mass-measurement techniques faced limitations in achieving high precision for ultralow-volume liquids due to complex internal fluid flows and viscous effects. By analyzing the ultrahigh-frequency longitudinal waves, the researchers succeeded in excluding the effects of viscosity and precisely isolating and measuring the pure mass component.

When applied to human aqueous humor, the technique clearly revealed interindividual differences in physical properties. This finding suggests that the physical properties of aqueous humor are closely related to an individual’s physiological state and ocular diseases.

Unlike conventional liquid biopsy approaches that focus on biochemical molecular information such as proteins or genes, this study proposes a new concept of "physical liquid biopsy," which analyzes physical properties of biofluids—mass, density, solute concentration, and viscosity—to assess health status and disease information. This represents significant academic and medical implications.

Because the required sample volume is extremely small, the technique is expected to be widely applicable not only to biofluids with limited available volume, such as aqueous humor, but also to the analysis of various other trace biofluids. The research team plans to expand the application of this technique beyond ocular disease diagnosis to develop diagnostic technologies for various diseases using ultralow-volume biofluids.

The study, titled "Nanomechanical gravimetric analysis of single microdroplets for liquid biopsy," was published in ACS Sensors, a leading journal of the American Chemical Society, on August 28. (JCR top 4.1%, impact factor 10.9)

This research was supported by the National Research Foundation of Korea, the Ministry of Education’s G-LAMP program, the Korea Agency for Science and Technology Commercialization and Promotion, the Research Equipment Specialized Personnel Training Program, and the Institute for Information & Communications Technology Planning and Evaluation’s University ICT Research Center Support Program.