A research team has developed a label-free surface-enhanced Raman scattering (SERS) analysis technology that rapidly detects extremely low concentrations of viable bacteria by directly growing plasmonic metal nanostructures on and around bacterial cells.
The technology enables trace levels of bacteria to be detected within one hour without conventional culture-based amplification and could also assess bacterial responses to antibiotics within two hours. It is expected to provide a foundation for rapid diagnosis of severe infectious diseases such as sepsis and for more precise selection of antibiotic treatments.
The research team is led by senior researcher Minyoung Lee and principal researcher Sunggyu Park of the Advanced Bio and Healthcare Materials Research Division at the Korea Institute of Materials Science (KIMS).
Sepsis is a life-threatening condition in which the body’s dysregulated response to infection leads to organ dysfunction. Rapid identification of the causative pathogen and timely administration of an effective antibiotic are therefore critical. During the early stages of infection, however, bacterial concentrations in the bloodstream can be extremely low, making direct detection difficult. Conventional blood culture testing requires bacteria in a blood sample to be grown before the causative organism and an appropriate antibiotic can be identified, meaning that results may take hours or several days. This has created strong demand for technologies capable of rapidly detecting viable pathogens and determining which antibiotics are effective.
KIMS previously developed highly sensitive biosensor technologies that use three-dimensional plasmonic nanostructures to detect protein biomarkers associated with sepsis in blood. The new research goes a step further by directly detecting viable causative bacteria themselves rather than disease-associated biomarkers and by rapidly evaluating their response to antibiotics.
To achieve this, the research team developed a SERS analysis approach in which bacterial cells themselves serve as nucleation sites for nanostructure growth. Plasmonic metal nanostructures are formed directly on and around bacterial cells, creating highly localized electromagnetic enhancement and amplifying the bacteria’s intrinsic Raman signals. The researchers progressively advanced the technology through three stages: growing nanostructures around bacteria in solution, directly depositing metal nanostructures onto bacterial surfaces, and finally integrating bacterial separation and enrichment with additional in situ nanostructure growth. This stepwise development substantially improved the ability to detect bacteria at extremely low concentrations.
SERS is an analytical technique that amplifies the weak Raman signals characteristic of a material by using intense electromagnetic fields known as plasmonic hot spots, which form in nanoscale gaps between metallic nanostructures such as gold or silver. Conventional SERS approaches face an inherent structural mismatch: plasmonic hot spots are typically only a few to tens of nanometres in size, whereas bacterial cells are approximately one micrometre in scale. As a result, only a small portion of a bacterial surface may come into contact with the signal-enhancing region. Rather than attempting to position a bacterium precisely within pre-existing nanoscale hot spots, the KIMS team reversed the approach. By directly forming plasmonic hot spots where the bacteria are located, the researchers significantly amplified the intrinsic Raman signals of bacterial cells without requiring separate labelling agents.
The team first developed a method for growing metal nanostructures around bacteria suspended in solution and then used electrochemical deposition to form metal nanostructures directly on bacterial surfaces. By combining the resulting SERS spectra with artificial intelligence-based analysis, the researchers were able to distinguish among eight different bacterial species. The electrochemically engineered platform directly creates plasmonic hot spots on captured bacterial surfaces, addressing the spatial mismatch between bacterial cells and conventional SERS-active nanogaps.
The researchers subsequently developed a filtration-integrated SERS substrate that captures and concentrates bacteria in a localised area and then grows plasmonic nanostructures around them to amplify their signals. By integrating separation, enrichment, and detection on a single substrate, the platform successfully detected bacteria at concentrations as low as approximately 1–10 colony-forming units per millilitre (CFU/mL). The latest platform also demonstrated the potential for rapid antimicrobial susceptibility assessment based on changes in SERS signal intensity associated with bacterial viability.
The team further confirmed bacterial detection performance in bacteria-spiked serum and urine samples. By analysing changes in SERS signals after exposing the bacteria to antibiotics, the researchers also demonstrated the potential to evaluate antibiotic response within two hours. Going forward, the team plans to conduct clinical validation using blood samples from patients with bloodstream infections and sepsis. The goal is to develop an integrated rapid precision-diagnostic platform that combines direct pathogen detection with antimicrobial susceptibility testing.
“The key to this research is that we directly grow nanostructures where the bacteria are located and combine this approach with separation and enrichment technologies to overcome the limitations of detecting extremely low bacterial concentrations,” Lee said.
“Our next goal is to rapidly identify causative pathogens directly in blood samples from patients with infections and evaluate their response to antibiotics, ultimately helping clinicians make faster treatment decisions for sepsis.”
“The central achievement of this work is that we directly formed the signal-enhancing plasmonic nanostructures on and around bacterial surfaces, thereby overcoming a fundamental structural limitation of conventional SERS,” Park said.
“We plan to further develop the technology into an ultrasensitive infectious-disease diagnostic platform that can ultimately be used in real clinical environments.”
“This achievement is particularly meaningful because it demonstrates how advanced materials technologies can help address a major clinical challenge: the rapid diagnosis of infectious diseases,” said KIMS president Chul-jin Choi.
“KIMS will continue to actively support the convergence of materials and biotechnology so that our research can contribute both to public health and to strengthening the competitiveness of Korea’s bio and medical-device industries.”