About

Ellen M. Sletten received her BS in Chemistry from Stonehill College in 2006 and completed her PhD at the University of California, Berkeley under Prof. Carolyn Bertozzi. Her doctoral work involved the optimization and development of bioorthogonal chemistries and their applications in labeling living systems. After earning her PhD in 2011, she conducted postdoctoral studies in the laboratory of Prof. Tim Swager at MIT as an NIH Postdoctoral Fellow. She joined UCLA as an Assistant Professor and the John T. McTague Career Development Chair in 2015. Her research group exploits the unique properties of fluorinated materials to develop diagnostic and therapeutic technologies, integrating disciplines such as organic synthesis, fluorous chemistry, chemical biology, nanoscience, supramolecular chemistry, polymer synthesis, photophysics, and pharmacology.

Research topics

• Chemistry
• Materials science
• Nanotechnology
• Combinatorial chemistry
• Optoelectronics

Selected publications

• Chromenylium and Flavylium Polymethine Fluorophores Light Up the Shortwave Infrared Region

  Accounts of Chemical Research · 2026-04-16

  articleOpen accessSenior authorCorresponding

  ConspectusThe shortwave infrared (SWIR or NIR-II) region of the electromagnetic spectrum is exceptional for performing fluorescence imaging through skin and tissue. These long, low-energy wavelengths of light provide higher contrast, sensitivity, and imaging depth compared to visible and near infrared light. Though the advantages of SWIR imaging are well established, imaging setups are often custom-built, and there are currently no FDA-approved SWIR fluorophores. It is, however, an exciting time for fluorescence imaging in the clinic. With several new FDA-approved fluorophores in recent years, there is growing interest in advancing the landscape of fluorescence imaging for both diagnostic and therapeutic pursuits. To translate SWIR imaging from fundamental science to clinical applications, progress in both imaging technology and contrast agent design are two crucial, intimately linked factors.This Account details our journey to design biocompatible SWIR-emissive chromenylium- and flavylium-based polymethine fluorophores. Classically, the low band gaps and extended structural conjugation required to achieve SWIR emission compromise the brightness, stability, and aqueous solubility of organic dyes. The driving hypothesis of these studies is that rigorous structural derivatization can illuminate key design principles to overcome these challenges and generate bright, water-soluble, and functional SWIR dyes. Our story begins with Flav7, the first SWIR fluorophore specifically designed for in vivo imaging. We then detail lessons in heterocycle and polymethine linker design principles. From this, 7-, 2-, and C4′-position modifications provided insights for modulating the peak absorption wavelength (λmax,abs) and fluorescence quantum yield (ΦF). Since chromenylium and flavylium polymethine dyes maintain high absorption coefficients (εmax), their total brightness (εmax × ΦF) is excellent. Overall, the chromenylium dyes (e.g., Chrom7) proved to be a privileged scaffold for SWIR imaging. To maximize both fluorescence signal and multiplexing abilities, we focused on matching the λmax,abs of fluorophores to commercial laser lines. This approach has enabled high resolution excitation-based multiplexed imaging with up to five fluorophores in mice in real time, at video frame rates.Building on these design principles, this Account then highlights our strategies to achieve water-soluble and functional SWIR-emissive dyes. We leverage late-stage click chemistry to install hydrophilic moieties via two distinct approaches: 1) small, charged groups or 2) short poly(2-methyl-2-oxazoline) polymer chains. The first strategy resulted in small-molecule dyes SulfoChrom7, AmmonChrom7, and PhosphoChrom7 with diverse functionalities, while the second gave a unique star polymer architecture named “chromenylium star” or “CStar” (CStar30). With optimized bright, functional, and water-soluble dyes in hand, we look toward clinical applications in vascular imaging with SulfoChrom7, lymphatic imaging with CStar30, bone imaging with PhosphoChrom7, and in vivo cell tracking with AmmonChrom7. Finally, we propose that excitation-multiplexed image-guided surgery in the SWIR region can advance existing clinical technologies. Broadly, we anticipate chromenylium and flavylium fluorophores to continue to light up the SWIR region, signaling a new era in optical imaging.

  PublisherDOI

• Defining optimal wavelengths and probes for imaging through tissue using chromenylium polymethine dyes

  2026-03-05

  article1st authorCorresponding
  PublisherDOI

• Trinuclear Heptamethine Dyes for Shortwave Infrared In Vivo Imaging

  Angewandte Chemie · 2026-02-24

  articleSenior author

  ABSTRACT The term polymethine dye (PMD) has been intimately connected to the dinuclear scaffold–two heterocycles linked together by a polymethine chain of varying length. Dinuclear PMDs have been a successful scaffold for noninvasive in vivo imaging in the biologically advantageous near infrared (NIR) and shortwave infrared (SWIR) regions of the electromagnetic spectrum. Trinuclear PMDs, resulting from the addition of a third heterocycle into the polymethine chain, possess the same photophysical properties that make dinuclear dyes excellent fluorescent probes, but have yet to be investigated for in vivo imaging. Herein, we expand upon the dinuclear and trinuclear heptamethine dye scaffolds by taking advantage of the increased reactivity of a cyclopentenyl linker and synthesizing flavylium‐ and chromenylium‐based SWIR‐emitting fluorophores. The trinuclear scaffold instills the fluorophores with increased steric bulk, leading to beneficial photophysical properties in micelles and outperforming their classic dinuclear counterparts. In this work, we apply trinuclear PMDs for in vivo SWIR imaging in mice and find them to be particularly efficient at lymph node labeling upon intravenous administration.

  PublisherDOI

• Exploring the Role of Excitonic Coupling in Polariton Formation

  ChemRxiv · 2026-04-15

  articleOpen access

  J-aggregates are supramolecular structures assembled from organic chromophores, where collective interactions among monomeric units yield novel photophysical properties such as ultranarrow linewidths, increased peak absorption coefficients, and superradiant emission. J-aggregates are often used as substrates to prepare exciton-polaritons, hybrid quasiparticles formed by strongly coupled light and material excitations. However, the role of aggregation in exciton-polariton formation is often overlooked. In this work, we fabricate planar, Fabry-Pérot cavities containing a monomeric and J-aggregated thiacarbocyanine dye and perform angle-resolved transmission spectroscopy to elucidate the role of intermolecular dipolar coupling on polariton formation. We find that the monomer and J-aggregate cavities display similar coupling strengths of ℏΩ R = 168 ± 4 meV and ℏΩ R = 203 ± 1 meV, respectively. Most coupling criteria suggest that both monomer and J-aggregate cavities display strongly coupling. However, the J-aggregate cavity displays narrowed transmission peaks with distinctive anticrossing in both the experimental transmission and simulated absorptance, while the monomer does not. We ultimately classify the monomer as intermediately coupled while the J-aggregate is clearly strongly coupled. Our results suggest that excitonic coupling among monomers in J-aggregates mitigates inhomogeneous disorder effects and facilitates polariton formation, ultimately reinforcing J-aggregates as optimal molecular substrates for strong coupling experiments, particularly those aimed at leveraging delocalization effects.

  PublisherDOI

• 25 years of chemistry that simply clicks

  Nature · 2026-05-06

  articleSenior authorCorresponding
  PublisherDOI

• Counterion-Enhanced Brightness of Fluorous-Soluble Heptamethine Cyanine Dyes for Near- and Shortwave Infrared Fluorescence Imaging

  Chemical & Biomedical Imaging · 2026-02-26

  articleOpen accessSenior authorCorresponding

  Fluorescence imaging across the near-infrared (NIR, 700–1000 nm) and shortwave infrared (SWIR, 1000–2000 nm) regions offers significant advantages for biomedical applications. Over the past decade, we have advanced a unique class of fluorophores–deemed fluorofluorophores–that are soluble in the fluorous phase. The unique properties of the fluorous phase, including low polarizability and high oxygen content, render this medium challenging for fluorophore brightness and photostability. However, the low dielectric constant of perfluorocarbon solvents causes the counterion to play a significant role in the resulting photophysical properties, offering a nontraditional avenue for fluorophore optimization. Here, we demonstrate that counterion exchange provides a straightforward strategy to enhance the brightness of two fluorous-soluble heptamethine cyanine dyes for NIR and SWIR imaging. Exchanging a chloride counterion with bulkier fluorinated aryl borate counterions boosts the brightness up to 10-fold and photostability up to 60-fold in perfluorooctyl bromide. We showcase the utility of these bright, NIR fluorofluorophores for imaging perfluorocarbon nanoemulsion uptake in macrophage cells, visualizing droplet actuation for mechanobiology studies in zebrafish, and mapping vasculature using high-resolution SWIR detection in mice. Overall, this simple modification provides a practical approach to optimize fluorofluorophores for in vivo imaging without the need to redesign the entire fluorophore scaffold.

  PublisherDOI

• Trinuclear Heptamethine Dyes for Shortwave Infrared In Vivo Imaging

  Angewandte Chemie International Edition · 2026-02-17 · 1 citations

  articleOpen accessSenior authorCorresponding

  The term polymethine dye (PMD) has been intimately connected to the dinuclear scaffold-two heterocycles linked together by a polymethine chain of varying length. Dinuclear PMDs have been a successful scaffold for noninvasive in vivo imaging in the biologically advantageous near infrared (NIR) and shortwave infrared (SWIR) regions of the electromagnetic spectrum. Trinuclear PMDs, resulting from the addition of a third heterocycle into the polymethine chain, possess the same photophysical properties that make dinuclear dyes excellent fluorescent probes, but have yet to be investigated for in vivo imaging. Herein, we expand upon the dinuclear and trinuclear heptamethine dye scaffolds by taking advantage of the increased reactivity of a cyclopentenyl linker and synthesizing flavylium- and chromenylium-based SWIR-emitting fluorophores. The trinuclear scaffold instills the fluorophores with increased steric bulk, leading to beneficial photophysical properties in micelles and outperforming their classic dinuclear counterparts. In this work, we apply trinuclear PMDs for in vivo SWIR imaging in mice and find them to be particularly efficient at lymph node labeling upon intravenous administration.

  PublisherOA PDFDOI

• Carboranes without Cage Carbons: closo-Dodecaborate Mimics of Neutral closo-Carboranes

  ChemRxiv · 2025-03-19

  preprintOpen access

  Substituted two-dimensional aromatic systems, such as arenes, exhibit well-established reactivity patterns at specific sites, largely due to the pronounced electronic directing effects of attached substituents. In contrast, the regioselectivity of three-dimensional aromatic molecules as a function of substituents remains less understood and documented. In this work, we demonstrate that a series of closo-dodecaborate ([B12H12]2-) cluster isomers containing two -NMe₃⁺ moieties exhibit unprecedented regioselective reactivity at boron vertices farthest from the charged substituents. Through a combination of theoretical and experimental studies, we reveal that these boron clusters display near-perfect regioselectivity with multiple electrophiles, ultimately enabling vertex differentiation chemistry within these systems. This observed phenomenon closely parallels the reactivity patterns typically associated with icosahedral closo-carboranes, where a carbon-based vertex induces a strong electronic dipole, leading to pronounced vertex-specific reactivity differences at boron sites. Our findings suggest that these modified closo-dodecaborates serve as electronic analogs of closo-carboranes, achieving similar electronic directing effects without the need for cage-based carbon atoms. Instead, exopolyhedral substituents alone govern the regioselective behavior, expanding the potential for tailored functionalization in boron cluster chemistry.

  PublisherOA PDFDOI

• Acid-cleavable poly(oxazoline) surfactants

  Polymer Chemistry · 2025-01-01 · 2 citations

  articleOpen accessSenior authorCorresponding

  The acidic tumor microenvironment and late endosomes present a promising target for stimuli-responsive nanotherapeutics. Acid-cleavable surfactants, particularly those with hydrazone linkages, offer enhanced stability outside the cell while enabling efficient intracellular payload release. Their acid-triggered cleavage and cationic byproducts facilitate endosomal escape, making them attractive for cancer nanomedicine. Herein, we report the synthesis of a new hydrazone-linked poly(oxazoline)-based diblock copolymer surfactant. This surfactant cleaves in a pH-dependent manner going from pH 7.4 down to pH 5.0, where after 21 h, 80% ± 3% of the hydrazone-linked polymer remained at pH 7.4 compared to 17% ± 2% at pH 5.0. We then demonstrate the ability of nanoemulsion encapsulated payloads to partition into cell membrane mimics only after cleavage of the surfactant. Through this system, we were able to increase the amount of payload release from 26% to 47% over 42 hours through pH changes. In all, this work demonstrates a viable route to create POx-based nanomaterials with controlled release capabilities in biologically relevant conditions and is a promising platform for advancing the endosomal escape and cancer targeting of nanomaterials.

  PublisherOA PDFDOI

• High-Resolution Multicolor Shortwave Infrared Dynamic <i>In Vivo</i> Imaging with Chromenylium Nonamethine Dyes

  Journal of the American Chemical Society · 2025-05-09 · 17 citations

  articleOpen accessSenior authorCorresponding

  Imaging in the shortwave infrared (SWIR) region offers fast, high-resolution visualization of in vivo targets in a multiplexed manner. These methods require bright, bathochromically shifted fluorescent dyes with sufficient emission at SWIR wavelengths–ideally above 1500 nm for high-resolution deep tissue imaging. Polymethine dyes are a privileged class of contrast agents due to their excellent absorption and high degree of modularity. In this work, we push flavylium and chromenylium dyes further into the SWIR region through polymethine chain extension. This panel of nonamethine dyes boasts absorbances as red as 1149 nm and tail emission beyond 1500 nm. These dyes are the brightest organic fluorophores at their respective bandgaps to date, with εmax ∼ 105 M–1 cm–1 and ΦF up to 0.5%. Using two nonamethine dyes, Chrom9 and JuloFlav9, we performed two-color all-SWIR multiplexed imaging (Excitation at 1060 and 1150 nm; Emission collection at >1500 nm), enhancing the depths and resolutions able to be obtained in multicolor SWIR imaging with small molecule contrast agents. Finally, we combine the nonamenthine dyes with other SWIR-emissive fluorophores and demonstrate five-color awake imaging in an unrestrained mouse, simultaneously pushing the multiplexing, resolution, and speed limits of in vivo optical imaging.

  PublisherDOI

Recent grants

• Bioorthogonal host-guest chemistry for tandem imaging and therapy

  NIH · $2.3M · 2018–2023

• Engineering cyanine aggregation and self-assembly to access exceptionally red-shifted organic chromophores

  NSF · $545k · 2019–2023

• Fluorous mediated J aggregation as a bright NIR target specific imaging agent

  NIH · $96k · 2012–2014

• Robust microdroplet-based mechanical probes for wide-ranging mechanobiology applications

  NIH · $1.8M · 2019–2025

• Biocompatible fluorophores for shortwave infrared imaging

  NIH · $323k · 2022–2023

Frequent coauthors

• Carolyn R. Bertozzi

  Stanford University

  53 shared

• Justin R. Caram

  44 shared

• Oliver T. Bruns†

  Helmholtz-Zentrum Dresden-Rossendorf

  41 shared

• Timothy L. Atallah

  University of California, Los Angeles

  38 shared

• Timothy M. Swager

  Massachusetts Institute of Technology

  34 shared

• Emily D. Cosco

  Stanford University

  32 shared

• Monica Pengshung

  University of California, Los Angeles

  29 shared

• Bernardo A. Arús

  Helmholtz-Zentrum Dresden-Rossendorf

  26 shared

Labs

• Sletten GroupPI

Awards & honors

• Chan Zuckerberg Initiative Grant, 2024
• Distinguished Teaching Award, 2023
• WCC Rising Star Award, 2023
• Agnes Fay Morgan Research Award, 2022
• Herbert Newby McCoy Award, 2021