About

My lab focuses on the development, assessment and clinical translation of new nano-based molecular imaging strategies to help clinicians detect cancers with better sensitivity and specificity. These molecular imaging tools are directed at: 1) Improving early cancer detection during routine screening techniques 2) Helping surgeons identify and resect tumor margins with better sensitivity and specificity 3) Enabling better drug discovery and personalized medicine using novel multiplexed imaging techniques.

Research topics

• Computer Science
• Materials science
• Nanotechnology
• Artificial Intelligence
• Medicine
• Biology
• Chemical engineering
• Physics
• Risk analysis (engineering)
• Engineering
• Chemistry
• Optics
• Internal medicine

Selected publications

• Optimization of Biodegradable Nanoparticles for Fluorescent Imaging with Drug and Cosmetic Coloring Dye Green 8

  ACS Nano Medicine · 2026-01-29

  articleSenior author
  PublisherDOI

• Enhancing fluorescence-guided surgery with biodegradable NPs encapsulating coloring dye Green 8

  2026-03-05

  article

  Accurate visualization of tumor margins is critical during surgical resection to reduce recurrence and improve patient outcomes. Clinically approved fluorescent dyes like Indocyanine Green and Methylene Blue are limited by low brightness, poor specificity, and rapid clearance. In this study, we developed biodegradable nanoparticles encapsulating Green 8 (G8), an FDA-approved drug and cosmetic dye with significantly higher fluorescence than existing clinical agents. Two nanoparticle platforms—silica-based and liposomal—were fabricated and characterized for size, stability, and optical properties. Liposomal G8 nanoparticles exhibited superior fluorescence intensity and biocompatibility and were selected for in vivo testing in an oral squamous cell carcinoma (OSCC) xenograft model. Following intravenous administration, G8 liposomes demonstrated strong tumor accumulation via the enhanced permeability and retention (EPR) effect and significantly higher tumor-to-background contrast compared to free dye. These findings support the translational potential of G8-loaded liposomes as a bright and cost-effective contrast agent for fluorescence-guided surgery.

  PublisherDOI

• Nitrogen Positioning in Bicyclic Aromatic Ligands Governs Binding to Nano-Gold: A Curious Case of Quinolinethiol

  Chemistry of Materials · 2026-01-26

  articleOpen access

  Understanding how small aromatic ligands bind to noble-metal surfaces is critical for engineering plasmonic nanomaterials for sensing, catalysis, and biomedical applications. Here, we systematically investigate how nitrogen heteroatoms─and their positional placement within fused bicyclic molecules (Bm)─govern anchoring, orientation, and functionalization on colloidal gold nanoparticles (AuNPs). Surface-enhanced Raman scattering (SERS) is used as an in situ probe of adsorption motifs, while density functional theory (DFT) calculations quantify adsorption energies, preferred geometries, and chemical enhancement contributions using a Au20 cluster model. The Bm library comprises (i) a non-nitrogen thiolated reference (2-naphthalenethiol, 2-NT), (ii) thiolated nitrogen-containing quinolinethiols (2-QTH and 8-QTH), and (iii) nonthiolated nitrogen-functionalized naphthols (AN, NN, and NNA). Combined theoretical and experimental analyses reveal how molecular architecture controls binding strength, adsorption geometry, colloidal stability, and SERS performance. Three distinct interaction regimes emerge: strong bidentate anchoring for 2-QTH via cooperative Au–S and Au–N coordination (∼2.3 Å), monodentate π-stacking for 2-NT and 8-QTH (∼2.5 Å), and weak physisorption for nonthiols (∼3.2 Å). We further introduce a transferable descriptor, D*χ, linking molecular energetics with surface affinity and functionalization density. Overall, the results demonstrate that nitrogen positioning critically determines molecule–gold interactions and provide quantitative design rules for robust ligand anchoring and stable plasmonic interfaces.

  PublisherDOI

• Benchtop Fabrication and Integration of Laser‐Induced Graphene Strain Gauges and Stimulation Electrodes in Muscle on a Chip Devices

  Advanced Functional Materials · 2025-02-24 · 10 citations

  articleOpen access

  Abstract Muscle on a Chip devices are valuable research tools for interrogating the structure and physiology of engineered heart, skeletal, or smooth muscle tissue constructs from the molecular to the multi‐cellular level. However, many existing devices rely on functional assays with limited throughput, such as optical microscopy, to measure contractility. Although electrical components have been integrated to automate recordings in advanced devices, their fabrication typically requires specialized equipment found in cleanroom facilities. In this work, miniature strain gauges are engineered to record the contractions of engineered skeletal muscle bundles using only benchtop fabrication equipment. A commercial CO 2 laser is employed to generate patterns of laser‐induced graphene (LIG) on polyimide (PI) films. LIG is then transferred from PI to thin polydimethylsiloxane (PDMS) films to make conductive and intrinsically flexible and stretchable layers that demonstrate long‐term stability under repeated cycles of stretch. Engineered skeletal muscle bundles are anchored to LIG‐PDMS strain gauges and their contraction is sensed in response to electrical stimulation, which is delivered by LIG‐PI stimulation electrodes also integrated into the device. Collectively, these results demonstrate that LIG is an attractive material for rapidly and inexpensively integrating electrical components for in situ strain sensing and electrical stimulation in Muscle on a Chip devices.

  PublisherOA PDFDOI

• Multiphoton Luminescence Imaging: A Label-Free Tool for Visualizing the Long-Term Fate of Gold Nanoparticles in Tissue

  ACS Nano · 2025-08-04 · 4 citations

  articleOpen accessSenior authorCorresponding

  Gold nanoparticles (AuNPs) are increasingly used in applications across the biomedical domain, yet their long-term biodistribution and biocompatibility remain poorly understood. Conventional brightfield microscopy imaging techniques often fail to detect AuNPs due to optical diffraction limits and lack of chromogenic contrast. Understanding the biodistribution and ultimate fate of these nonbiodegradable NPs is crucial for further development of AuNP-based therapeutics and diagnostics. Here, we present a label-free multiphoton luminescence (MPL) imaging workflow that enables sensitive detection of AuNPs in liver histology sections, even 1 year after intravenous (IV) administration. MPL imaging exploits the intrinsic nonlinear optical properties of AuNPs to generate broadband emission under ultrafast pulsed laser excitation, enabling subcellular localization without exogenous labels while having the ability to rapidly image entire organ sections. The intrinsic, distinct broadband MPL emission produced by gold allows us to study these NPs in their biological context without extrinsic labels while also faithfully representing the surrounding tissue architecture via autofluorescence and second harmonic generation. We demonstrate that MPL imaging detects up to 98% more AuNP-positive regions than brightfield microscopy in challenging low-dose (1 nM) conditions and requires no modification of standard histology workflows. Correlative imaging with SEM-EDS confirms high spatial specificity (AUC = 0.955) of MPL for AuNP localization. Dose-dependent retention patterns were observed across liver tissue, and MPL analysis showed strong correlation with ICP-MS quantification. Importantly, histological and immunohistochemical analyses (Masson's trichrome, CD3, and TUNEL) revealed no significant fibrosis, immune activation, or apoptosis in liver tissue at either low (1 nM) or high (10 nM) doses at 1 year post IV administration. These findings establish MPL imaging as a robust, label-free tool for long-term tracking of AuNPs in biological tissue and highlight its potential for improving biodistribution and safety assessments.

  PublisherOA PDFDOI

• A Permeabilization Workflow To Enable Specific Multiplexed Profiling Using SERS Nanoparticles

  ACS Applied Materials & Interfaces · 2025-06-17

  articleOpen accessSenior authorCorresponding

  Surface-enhanced Raman scattering nanoparticles (SERS NPs) are powerful tools for cellular-specific targeting and multiplexed biomarker detection. While they have been effective in labeling extracellular receptors, their application to intracellular targets has been limited by poor membrane permeability and endosomal trapping. Here, we present an optimized permeabilization and staining strategy that enables robust intracellular targeting with SERS NPs. Using breast cancer as a model system, we focused on three clinically relevant biomarkers─human epidermal growth factor 2 (HER2), which has both extracellular and intracellular targets, and estrogen receptor (ER) and progesterone receptor (PR), which are exclusively located inside the cells─to demonstrate the ability of our platform to detect both extracellular and intracellular targets. We conjugated SERS NPs with anti-HER2 antibodies to assess specific binding efficiency across breast cancer cell lines with varying HER2 expression. Flow cytometry revealed a strong correlation between HER2 expression and the specific-to-nonspecific binding ratio, demonstrating over 100-fold specificity for HER2-overexpressing cells. Fluorescence and Raman imaging confirmed high specificity and sensitivity. To extend this approach to intracellular targets, we evaluated three permeabilization agents─Tween 20, Triton X-100, and methanol─and identified Triton X-100 as optimal. It enabled ∼160 nm SERS NPs to access the intracellular space while preserving cell viability. SERS NPs conjugated with anti-ER and anti-PR antibodies revealed significant biomarker binding without compromising cell health, revealing the capability to specifically profile intracellular biomarkers with varying expression levels of ER and PR. Furthermore, multiplexed detection was demonstrated using a cocktail of SERS NPs targeting HER2, ER, and PR in mixed cell populations, mimicking clinical scenarios such as liquid biopsies. Even when target-positive cells were present at low abundance, the NPs retained selective binding and detection capability. Overall, our findings advance the potential of SERS NPs for enhancing breast cancer diagnostics through accurate, multiplexed biomarker targeting.

  PublisherOA PDFDOI

• A Systematic Approach toward Enabling Maximal Targeting Efficiency of Cell Surface Proteins with Actively Targeted SERS Nanoparticles

  ACS Applied Materials & Interfaces · 2024-03-20 · 10 citations

  articleOpen accessSenior authorCorresponding

  With their intricate design, nanoparticles (NPs) have become indispensable tools in the quest for precise cellular targeting. Among various NPs, gold NPs stand out with unique features such as chemical stability, biocompatibility, adjustable shape, and size-dependent optical properties, making them particularly promising for molecular detection by leveraging the surface-enhanced Raman scattering (SERS) effect. Their multiplexing abilities for the simultaneous identification of multiple biomarkers are important in the rapidly evolving landscape of diverse cellular phenotypes and biomolecular profiling. However, the challenge is ensuring that SERS NPs can effectively target specific cells and biomarkers among intricate cell types and biomolecules with high specificity. In this study, we improve the functionalization of SERS NPs, optimizing their targeting efficiency in cellular applications for ca. 160 nm NP-based probes. Spherical SERS NPs, conjugated with antibodies targeting epidermal growth factor receptor and human epidermal growth factor receptor 2, were incubated with cells overexpressing these proteins, and their specific binding potential was quantified at each stage by using flow cytometry to achieve optimal targeting efficiency. We determined that maintaining an average of 3.5 × 105 thiols per NP, 300 antibodies per NP, 18,000 NPs per cell, conducting a 15 min staining incubation at 4 °C in a shaker, and using SM(PEG)12 as a cross-linker for the NP conjugation were crucial to achieve the highest targeting efficiency. Fluorescence and Raman imaging were used with these parameters to observe the maximum ability of these NPs to efficiently target suspended cells. These highly sensitive contrast agents demonstrate their pivotal role in effective active targeting, making them invaluable for multiplexing applications across diverse biological environments.

  PublisherOA PDFDOI

• A Raman topography imaging method toward assisting surgical tumor resection

  npj Imaging · 2024-02-19 · 12 citations

  articleOpen accessSenior author

  Achieving complete tumor resection upon initial surgical intervention can lead to better patient outcomes by making adjuvant treatments more efficacious and reducing the strain of repeat surgeries. Complete tumor resection can be difficult to confirm intraoperatively. Methods like touch preparation (TP) have been inconsistent for detecting residual malignant cell populations, and fatty specimens like breast cancer lumpectomies are too fatty to process for rapid histology. We propose a novel workflow of immunostaining and topographic surface imaging of freshly excised tissue to ensure complete resection using highly sensitive and spectrally separable surface-enhanced Raman scattering nanoparticles (SERS NPs) as the targeted contrast agent. Biomarker-targeting SERS NPs are ideal contrast agents for this application because their sensitivity enables rapid detection, and their narrow bands enable extensive intra-pixel multiplexing. The adaptive focus capabilities of an advanced Raman instrument, combined with our rotational accessory device for exposing each surface of the stained specimen to the objective lens, enable topographic mapping of complete excised specimen surfaces. A USB-controlled accessory for a Raman microscope was designed and fabricated to enable programmatic and precise angular manipulation of specimens in concert with instrument stage motions during whole-surface imaging. Specimens are affixed to the accessory on an anti-slip, sterilizable rod, and the tissue surface exposed to the instrument is adjusted on demand using a programmed rotating stepper motor. We demonstrate this topographic imaging strategy on a variety of phantoms and preclinical tissue specimens. The results show detail and texture in specimen surface topography, orientation of findings and navigability across surfaces, and extensive SERS NP multiplexing and linear quantitation capabilities under this new Raman topography imaging method. We demonstrate successful surface mapping and recognition of all 26 of our distinct SERS NP types along with effective deconvolution and localization of randomly assigned NP mixtures. Increasing NP concentrations were also quantitatively assessed and showed a linear correlation with Raman signal with an R2 coefficient of determination of 0.97. Detailed surface renderings color-encoded by unmixed SERS NP abundances show a path forward for content-rich, interactive surgical margin assessment.

  PublisherOA PDFDOI

• The evolution of immune profiling: will there be a role for nanoparticles?

  Nanoscale Horizons · 2024-01-01 · 4 citations

  reviewOpen accessSenior authorCorresponding

  Immune profiling provides insights into the functioning of the immune system, including the distribution, abundance, and activity of immune cells. This understanding is essential for deciphering how the immune system responds to pathogens, vaccines, tumors, and other stimuli. Analyzing diverse immune cell types facilitates the development of personalized medicine approaches by characterizing individual variations in immune responses. With detailed immune profiles, clinicians can tailor treatment strategies to the specific immune status and needs of each patient, maximizing therapeutic efficacy while minimizing adverse effects. In this review, we discuss the evolution of immune profiling, from interrogating bulk cell samples in solution to evaluating the spatially-rich molecular profiles across intact preserved tissue sections. We also review various multiplexed imaging platforms recently developed, based on immunofluorescence and imaging mass spectrometry, and their impact on the field of immune profiling. Identifying and localizing various immune cell types across a patient's sample has already provided important insights into understanding disease progression, the development of novel targeted therapies, and predicting treatment response. We also offer a new perspective by highlighting the unprecedented potential of nanoparticles (NPs) that can open new horizons in immune profiling. NPs are known to provide enhanced detection sensitivity, targeting specificity, biocompatibility, stability, multimodal imaging features, and multiplexing capabilities. Therefore, we summarize the recent developments and advantages of NPs, which can contribute to advancing our understanding of immune function to facilitate precision medicine. Overall, NPs have the potential to offer a versatile and robust approach to profile the immune system with improved efficiency and multiplexed imaging power.

  PublisherOA PDFDOI

• Assessment of unmixing approaches for the quantitation of SERS nanoparticles in highly multiplexed spectral images

  Journal of Raman Spectroscopy · 2024-01-22 · 6 citations

  articleOpen accessSenior authorCorresponding

  Surface-enhanced Raman scattering nanoparticles (SERS NPs) offer powerful optical contrast features for imaging assays. Their gold core enhances the inelastic scattering cross section, allowing highly sensitive and rapid detection, and their characteristic sets of narrow spectral bands give them unsurpassed multiplexing capabilities. Multiplexed hyperspectral images are commonly unmixed using a compensation matrix of reference spectra to produce quantitative image channels illustrating the distribution of each material. It is these unmixed channels that are fit for interpretation from assays utilizing SERS NP contrast agents. Some factors that may impact SERS NP quantitative and dynamic range capabilities may include endogenous background heterogeneity, the ability of unmixing algorithms to account for signal variances, and linear system conditioning imposed by contrast agent signals. We report on hyperspectral Raman imaging of mixtures of SERS NPs from an expanded library of contrast agents. We study increasing plexity and varying degrees of system conditioning as inputs to a diverse set of classical, non-negatively constrained, and regularized regression algorithms to investigate which signal features and unmixing methods deliver the most promising quantitation performance with the least error. Raman imaging of SERS NP mixtures is performed on controlled substrates and representative biological specimens, and experimental results are compared against ground truth data. We evaluate spectral fitting fidelity, quantitation, and specificity correlations with system conditioning. Spectral unmixing with a regularized hybrid of least squares regression with principal component analysis (HLP) algorithm approximated spectra with 3.5× better fitting fidelity and 3× better quantitation robustness with tissue background compared with simpler unmixing routines.

  PublisherOA PDFDOI

Recent grants

• A New Raman-based Strategy to Identify Tumor Margins and Guide Surgical Resection

  NIH · $368k · 2015–2019

Frequent coauthors

• Olga E. Eremina

  University of Southern California

  43 shared

• Alexander Czaja

  University of Southern California

  38 shared

• Sanjiv S. Gambhir

  Stanford University

  38 shared

• Augusta Fernando

  Convergent Science (United States)

  26 shared

• Jos L. Campbell

  AbbVie (United States)

  22 shared

• Sean Burkitt

  University of Southern California

  18 shared

• Adam de la Zerda

  Stanford University

  14 shared

• Dominie Miyasato

  Harvard University

  14 shared

Labs

• Zavaleta LabPI

Education

• Ph.D.

  University of Southern California