Hee Sun Han

Compact high-quality CdSe–CdS core–shell nanocrystals with narrow emission linewidths and suppressed blinking

High particle uniformity, high photoluminescence quantum yields, narrow and symmetric emission spectral lineshapes and minimal single-dot emission intermittency (known as blinking) have been recognized as universal requirements for the successful use of colloidal quantum dots in nearly all optical applications. However, synthesizing samples that simultaneously meet all these four criteria has proven challenging. Here, we report the synthesis of such high-quality CdSe-CdS core-shell quantum dots in an optimized process that maintains a slow growth rate of the shell through the use of octanethiol and cadmium oleate as precursors. In contrast with previous observations, single-dot blinking is significantly suppressed with only a relatively thin shell. Furthermore, we demonstrate the elimination of the ensemble luminescence photodarkening that is an intrinsic consequence of quantum dot blinking statistical ageing. Furthermore, the small size and high photoluminescence quantum yields of these novel quantum dots render them superior in vivo imaging agents compared with conventional quantum dots. We anticipate these quantum dots will also result in significant improvement in the performance of quantum dots in other applications such as solid-state lighting and illumination.

Development of a Bioorthogonal and Highly Efficient Conjugation Method for Quantum Dots using Tetrazine-Norbornene Cycloaddition

We present a bioorthogonal and modular conjugation method for efficient coupling of organic dyes and biomolecules to quantum dots (QDs) using a norbornene-tetrazine cycloaddition. The use of noncoordinating functional groups combined with the rapid rate of the cycloaddition leads to highly efficient conjugation. We have applied this method to the in situ targeting of norbornene-coated QDs to live cancer cells labeled with tetrazine-modified proteins.

Synthesis of Cadmium Arsenide Quantum Dots Luminescent in the Infrared

We present the synthesis of Cd(3)As(2) colloidal quantum dots luminescent from 530 to 2000 nm. Previous reports on quantum dots emitting in the infrared are primarily limited to the lead chalcogenides and indium arsenide. This work expands the availability of high quality infrared emitters.

Quantum dot/antibody conjugates for in vivo cytometric imaging in mice

Significance One of the key questions in biology is understanding how cells move, interact, and evolve in living organisms. Tremendous efforts have been made to answer these questions in vitro, which have yielded a molecular-level understanding of cellular events. However, an increasing number of studies indicate that cellular activities need to be understood in the context of their natural environments. Single-cell labeling methods in use currently involve immunohistochemistry, genetic manipulation, or irradiation of mice, none of which reflect the native microenvironments. Here, we report quantum dot immunoconstructs that can be used for intravital imaging of single cells in unmanipulated mice and multiplexed in vivo cytometric analysis of rare cell populations. Multiplexed, phenotypic, intravital cytometric imaging requires novel fluorophore conjugates that have an appropriate size for long circulation and diffusion and show virtually no nonspecific binding to cells/serum while binding to cells of interest with high specificity. In addition, these conjugates must be stable and maintain a high quantum yield in the in vivo environments. Here, we show that this can be achieved using compact (∼15 nm in hydrodynamic diameter) and biocompatible quantum dot (QD) -Ab conjugates. We developed these conjugates by coupling whole mAbs to QDs coated with norbornene-displaying polyimidazole ligands using tetrazine–norbornene cycloaddition. Our QD immunoconstructs were used for in vivo single-cell labeling in bone marrow. The intravital imaging studies using a chronic calvarial bone window showed that our QD-Ab conjugates diffuse into the entire bone marrow and efficiently label single cells belonging to rare populations of hematopoietic stem and progenitor cells (Sca1+c-Kit+ cells). This in vivo cytometric technique may be useful in a wide range of structural and functional imaging to study the interactions between cells and between a cell and its environment in intact and diseased tissues.

Using nanowires to extract excitons from a nanocrystal solid

Synthetic methods yielding highly uniform colloidal semiconductor nanocrystals with controlled shapes and sizes are now available for many materials. These methods have enabled geometrical control of optical properties, which are difficult or impossible to achieve in conventional bulk solids. However, incorporating nanocrystals efficiently into photodetectors remains challenging because of the low charge carrier mobilities typical of nanocrystal solids. Here we present an approach based on exciton energy transfer from CdSe/CdS core/shell nanocrystals to embedded CdSe nanowires. By combining the wide electronic tunability of nanocrystals with the excellent one-dimensional charge transport characteristics obtainable in nanowires, we are able to increase photocurrent extraction from a nanocrystal solid by 2-3 orders of magnitude. Furthermore, we correlate local device morphology with optoelectronic functionality by measuring the local photocurrent response in a scanning confocal microscope. We also discuss how nancocrystal/nanowire hybrid devices could be used in particle detector systems.

Whole‐Genome Sequencing of a Single Viral Species from a Highly Heterogeneous Sample

Metagenomic studies suggest that only a small fraction of the viruses that exist in nature have been identified and studied. Characterization of unknown viral genomes is hindered by the many genomes populating any virus sample. A new method is reported that integrates drop-based microfluidics and computational analysis to enable the purification of any single viral species from a complex mixed virus sample and the retrieval of complete genome sequences. By using this platform, the genome sequence of a 5243 bp dsDNA virus that was spiked into wastewater was retrieved with greater than 96% sequence coverage and more than 99.8% sequence identity. This method holds great potential for virus discovery since it allows enrichment and sequencing of previously undescribed viruses as well as known viruses.

Erratum: Quantum dot/antibody conjugates for in vivo cytometric imaging in mice (Proceedings of the National Academy of Sciences of the United States of America (2015) 112 (1350-1355) doi: 10.1073/pnas.1421632111)

APPLIED BIOLOGICAL SCIENCES, CHEMISTRY Correction for “Quantum dot/antibody conjugates for in vivo cytometric imaging in mice,” by Hee-Sun Han, Elisabeth Niemeyer, Yuhui Huang, Walid S. Kamoun, John D. Martin, Jayeeta Bhaumik, Yunching Chen, Sylvie Roberge, Jian Cui, Margaret R. Martin, Dai Fukumura, Rakesh K. Jain, Moungi G. Bawendi, and Dan G. Duda, which appeared in issue 5, February 3, 2015, of Proc Natl Acad Sci USA (112:1350–1355; first published January 20, 2015; 10.1073/pnas.1421632111). The authors note that, due to a printer’s error, the affiliation for Moungi G. Bawendi should instead appear as “Department of Chemistry, Massachusetts Institute of Technology.” The corrected author and affiliation lines appear below. The online version has been corrected.