Research
FLOWER is currently capable of highly sensitive, label-free detection down to the level of a single, 15.4 kDa protein molecule (Figure 2). In addition to being able to detect biomolecules and particles in pure solutions, FLOWER has other advantages important for real-world sensing tasks. It is capable of sensitive detection of bioparticles in complex solutions such as mouse serum.
Key references:
Suebka, S., Gin, A., Su, Judith, Frequency Locked Whispering Evanescent Resonator (FLOWER) for biochemical sensing applications, Nature Protocols (accepted), (2024)
Gin, A., Nguyen, P-D., Melzer, J., Li, C., Strzelinski, H., Liggett, S.B., Su, Judith, Label-free, real-time monitoring of membrane binding events at zeptomolar concentrations using frequency-locked optical microresonators, Nature Communications, 15, 7445 (2024).
Gin, A., Nguyen, P-D., Serrano, G., Alexander, G, Su, Judith, Towards Early Diagnosis and Screening of Alzheimer’s Disease Using Frequency Locked Whispering Gallery Mode Microtoroid Biosensors, npj Biosensing, 1, 9 (2024).
Su, Judith, Goldberg. A.F, Stoltz, B.M. “Label-free single detection of single nanoparticles and biological molecules using microtoroid optical resonators,” Light: Science and Applications, 5, e16001 (2016).
Suebka, S., Nguyen, P-D, Gin, A, and Su, Judith, How fast it can stick: visualizing flow delivery to microtoroid biosensors, ACS Sensors, 7, 2700–2708, (2021), (supplementary cover)
Hao, S. and Su, Judith, Noise-induced limits of detection in frequency locked optical microcavities, Journal of Lightwave Technology, 38(22), 6393 – 6401 (2020).
United States Patent Numbers 9,737,770 and 10,309,960
Basic science
Our lab is interested in utilizing the high sensitivity and quick response time of our devices to study the basics of pain, olfaction, and taste.
Key references:
Yang, M-Y^, Mac, Khuong D.M^, Strzelinski, Hannah R., Hoffman, S.A., Kim, D., Kim, S-K, Su, Judith,* Liggett, S.B.*, III Goddard, W.A,* Agonist activation opening the Ga subunit of the GPCR–GProtein precoupled complex defines functional agonist activation of TAS2R5 GPCR, Proceedings of the National Academy of Sciences (PNAS), 121, e2409987121 (2024), ^co-first author, * co-corresponding author.
Hao, S., Guthrie, B., Kim, S-K, Kubicek, J., Murtaza, B., Khan, N.A., Khakbaz, P. , Su, Judith*, III Goddard, WA*, Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments, Communications Chemistry, 7, 236 (2024), co-corresponding author
Translational medicine
We have used FLOWER to successfully sense low concentrations of exosome (~ 40 nm nanovesicle) cancer biomarkers in mouse serum (Figure 3). In these experiments, female mice (n = 5) born on the same day were implanted with Daudi (human Burkitt’s lymphoma) tumor cells for 5 weeks. One microliter of serum from each mouse each week was diluted a million-fold in 0.9% saline and sequentially flowed over a microtoroid covalently functionalized with anti-CD81, an exosome-specific marker. A close inspection of a binding curve (Figure 4) shows discrete changes, or steps, in the resonance wavelength (λ) of the microtoroid as individual exosomes bind to the surface of the microtoroid.
Figure 3. Exosome binding curves. Mice were implanted with human Burkitt’s lymphoma tumor cells, and each week blood serum samples were taken and later analyzed all together using FLOWER. The curves shown here are from a single mouse. For each week we see an increase in the response from the sensor corresponding to increasing exosome levels. No significant signal was obtained from week 0. The data traces are fit with a simple exponential (dashed red line) corresponding to first-order kinetics.
Figure 4. FLOWER response data to a solution containing blood from a mouse with a tumor implanted in it for 5 weeks. (a) Zoom-in of week 5 and corresponding step-fit (red) and (b) histogram of step heights. Individual steps corresponding to the binding of individual exosomes may be seen. Negative step amplitudes represent step down or unbinding events.
Key references:
Hao, S., Su, Judith, Whispering gallery mode optical resonators for biological and chemical detection: current practices, future perspectives, and challenges, Reports on Progress in Physics, accepted, (2024)
Gin, A., Nguyen, P-D., Serrano, G., Alexander, G, Su, Judith, Towards Early Diagnosis and Screening of Alzheimer’s Disease Using Frequency Locked Whispering Gallery Mode Microtoroid Biosensors, npj Biosensing, 1, 9 (2024).
Kim, S-K, Suebka S., Gin A., Nguyen, P-D., Tang Y., Su, Judith*, III Goddard, WA*, Methotrexate inhibits the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain to the host cell angiotensin converting enzyme-2 (ACE-2) receptor, ACS Pharmacology & Translational Science, 7, 2, 348–362 (2024), *co-corresponding author (supplementary cover)
Luu, G., Ge., C., Tang, Y., Li, K., Cologna, S., Burdette, J., Su, Judith*, and Sanchez, L.*, An integrated approach to protein discovery and detection from complex biofluids, *co-corresponding author, Molecular & Cellular Proteomics, 2023
Dell’Olio, F., Su, Judith, Huser, T., Sottile, V., Alix-Panabières, C. Photonic technologies for liquid biopsies: recent advances and open research challenges, Laser & Photonics Reviews, 15, 2170012 (2021) (back cover).
Su, Judith, Label-free single exosome detection using frequency locked microtoroid optical resonators, ACS Photonics 2, 1241–1245 (2015).
Environmental monitoring
FLOWER has demonstrated part-per-trillion detection of toxic industrial chemicals and chemical warfare agent surrogates and precursors. This work is funded by the Defense Threat Reduction Agency (DTRA).
Key references:
Xu, Y, Stanko, A, Cerione, C, Lohrey, T, McLeod, E., Stoltz, B., Su, Judith, Low part-per-trillion, humidity resistant detection of nitric oxide using microtoroid optical resonators , ACS Applied Materials & Interfaces, 16, 4, 5120–5128 (2024)
Li, C., Lohrey, T.D., Nguyen, P-D., Min, Z., Tang, Y., Ge, C., Sercel, Z.P., McLeod, E., Stoltz, B.M., Su, Judith, Part-per-trillion trace selective gas detection using frequency locked whispering gallery mode microtoroids, ACS Applied Materials & Interfaces, 14, 37, 42430–42440 (2022) (supplementary cover).
Next generation sensing platforms
We work on building our next generation sensing platforms, this includes adding spectroscopic capabilities to our devices as well as working on ways to boost the sensitivity of our sensors.
Key references:
Hao, S, Suebka, S., Su, Judith, Single 5-nm quantum dot detection via microtoroid optical resonator photothermal microscopy Light: Science & Applications, 13, 195 (2024).
Choi, G. and Su, Judith, Impact of stimulated Raman scattering on dark soliton generation in a silica microresonator, J. Phys. Photonics, 5, 014001 (2023) (special issue on Emerging Leaders 2023).
Choi, G., Gin., A., and Su, Judith, Optical frequency combs in aqueous and air environments at visible to near-IR wavelengths, Optics Express, 30, 8690-8699 (2022)
Li, C., Chen, L., McLeod, E., Su, Judith, “Dark mode plasmonic optical microcavity biochemical sensor,” Photonics Research, 7(8), 939-947(2019).
Nguyen, P-D., Zhang, X., Su, Judith, One-step controlled synthesis of size-tunable toroidal gold particles for biochemical sensing, ACS Applied Nano Materials, 2(12), 7839-7847 (2019).
Portable, point-of-care, ultra-sensitive biosensors
In collaboration with the McLeod Laboratory, we are working to miniaturize these sensors, making them easily translatable to other labs and clinics.
Key references:
Suebka, S, McLeod, E., Su, Judith, Ultra-high-Q free space coupling to microtoroid resonators, Light: Science & Applications, 13, 75 (2024)
Chen, L., Li, C., Liu, Y., Su, Judith*, McLeod, E.* “Simulating robust far-field coupling to traveling waves in large three-dimensional nanostructured high-Q microresonators,” Photonics Research, 7 (9), 967-976 (2019), *co-corresponding author