Guosong Hong's research aims to bridge materials science and neuroscience, and blur the distinction between the living and non-living worlds by developing novel neuroengineering tools to interrogate and manipulate the brain in a minimally invasive way.

Guosong received his Ph.D. degree in chemistry from Stanford University in 2014 under the advice of Prof. Hongjie Dai. His Ph.D. research focused on the development of a new fluorescence imaging method in the second near-infrared window (NIR-II window, 1,000-1,700 nm) to afford deep-tissue penetration in the brain and other biological tissues. During his postdoctoral training at Harvard University with Prof. Charles Lieber, Guosong developed tissue-like mesh electronics neural probes to interrogate the brain and the retina with chronic stability, and is a recipient of the American Heart Association (AHA) Postdoctoral Fellowship and the NIH Pathway to Independence Award (K99/R00). Guosong joined the Stanford faculty in September 2018, and is an assistant professor of Materials Science and Engineering, and the Wu Tsai Neurosciences Institute.

Academic Appointments

Professional Education

  • Postdoc training, Harvard University, Chemistry and Chemical Biology (2018)
  • PhD, Stanford University, Chemistry (2014)

2019-20 Courses

Stanford Advisees

  • Postdoctoral Faculty Sponsor
    Fan Yang, Rongkang Yin
  • Doctoral Dissertation Advisor (AC)
    Paul Chong, Sang Cheol Kim, Kyrstyn Ong, Ajay Subramanian, Xiang Wu
  • Orals Evaluator
    Chris Lindsay
  • Master's Program Advisor
    Sang Cheol Kim, Zongqi Li, Yu-Ching Lin, Xiang Wu, Xinrui Zhang
  • Doctoral Dissertation Co-Advisor (AC)
    Ali Mahdi
  • Doctoral (Program)
    Siddharth Doshi, Kyrstyn Ong
  • Postdoctoral Research Mentor
    Rongkang Yin

All Publications

  • Tissue-like Neural Probes for Understanding and Modulating the Brain BIOCHEMISTRY Hong, G., Viveros, R. D., Zwang, T. J., Yang, X., Lieber, C. M. 2018; 57 (27): 3995–4004


    Electrophysiology tools have contributed substantially to understanding brain function, yet the capabilities of conventional electrophysiology probes have remained limited in key ways because of large structural and mechanical mismatches with respect to neural tissue. In this Perspective, we discuss how the general goal of probe design in biochemistry, that the probe or label have a minimal impact on the properties and function of the system being studied, can be realized by minimizing structural, mechanical, and topological differences between neural probes and brain tissue, thus leading to a new paradigm of tissue-like mesh electronics. The unique properties and capabilities of the tissue-like mesh electronics as well as future opportunities are summarized. First, we discuss the design of an ultraflexible and open mesh structure of electronics that is tissue-like and can be delivered in the brain via minimally invasive syringe injection like molecular and macromolecular pharmaceuticals. Second, we describe the unprecedented tissue healing without chronic immune response that leads to seamless three-dimensional integration with a natural distribution of neurons and other key cells through these tissue-like probes. These unique characteristics lead to unmatched stable long-term, multiplexed mapping and modulation of neural circuits at the single-neuron level on a year time scale. Last, we offer insights on several exciting future directions for the tissue-like electronics paradigm that capitalize on their unique properties to explore biochemical interactions and signaling in a "natural" brain environment.

    View details for DOI 10.1021/acs.biochem.8b00122

    View details for Web of Science ID 000438652900004

    View details for PubMedID 29529359

    View details for PubMedCentralID PMC6039269

  • A method for single-neuron chronic recording from the retina in awake mice SCIENCE Hong, G., Fu, T., Qiao, M., Viveros, R. D., Yang, X., Zhou, T., Lee, J., Park, H., Sanes, J. R., Lieber, C. M. 2018; 360 (6396): 1447-+


    The retina, which processes visual information and sends it to the brain, is an excellent model for studying neural circuitry. It has been probed extensively ex vivo but has been refractory to chronic in vivo electrophysiology. We report a nonsurgical method to achieve chronically stable in vivo recordings from single retinal ganglion cells (RGCs) in awake mice. We developed a noncoaxial intravitreal injection scheme in which injected mesh electronics unrolls inside the eye and conformally coats the highly curved retina without compromising normal eye functions. The method allows 16-channel recordings from multiple types of RGCs with stable responses to visual stimuli for at least 2 weeks, and reveals circadian rhythms in RGC responses over multiple day/night cycles.

    View details for DOI 10.1126/science.aas9160

    View details for Web of Science ID 000436598000073

    View details for PubMedID 29954976

    View details for PubMedCentralID PMC6047945

  • Mesh electronics: a new paradigm for tissue-like brain probes CURRENT OPINION IN NEUROBIOLOGY Hong, G., Yang, X., Zhou, T., Lieber, C. M. 2018; 50: 33–41


    Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to 'look and behave' like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies.

    View details for DOI 10.1016/j.conb.2017.11.007

    View details for Web of Science ID 000436225100006

    View details for PubMedID 29202327

    View details for PubMedCentralID PMC5984112

  • A bright organic NIR-II nanofluorophore for three-dimensional imaging into biological tissues NATURE COMMUNICATIONS Wan, H., Yue, J., Zhu, S., Uno, T., Zhang, X., Yang, Q., Yu, K., Hong, G., Wang, J., Li, L., Ma, Z., Gao, H., Zhong, Y., Su, J., Antaris, A. L., Xia, Y., Luo, J., Liang, Y., Dai, H. 2018; 9: 1171


    Fluorescence imaging of biological systems in the second near-infrared (NIR-II, 1000-1700 nm) window has shown promise of high spatial resolution, low background, and deep tissue penetration owing to low autofluorescence and suppressed scattering of long wavelength photons. Here we develop a bright organic nanofluorophore (named p-FE) for high-performance biological imaging in the NIR-II window. The bright NIR-II >1100 nm fluorescence emission from p-FE affords non-invasive in vivo tracking of blood flow in mouse brain vessels. Excitingly, p-FE enables one-photon based, three-dimensional (3D) confocal imaging of vasculatures in fixed mouse brain tissue with a layer-by-layer imaging depth up to ~1.3 mm and sub-10 µm high spatial resolution. We also perform in vivo two-color fluorescence imaging in the NIR-II window by utilizing p-FE as a vasculature imaging agent emitting between 1100 and 1300 nm and single-walled carbon nanotubes (CNTs) emitting above 1500 nm to highlight tumors in mice.

    View details for PubMedID 29563581

  • Mesh Nanoelectronics: Seamless Integration of Electronics with Tissues ACCOUNTS OF CHEMICAL RESEARCH Dai, X., Hong, G., Gao, T., Lieber, C. M. 2018; 51 (2): 309–18


    Nanobioelectronics represents a rapidly developing field with broad-ranging opportunities in fundamental biological sciences, biotechnology, and medicine. Despite this potential, seamless integration of electronics has been difficult due to fundamental mismatches, including size and mechanical properties, between the elements of the electronic and living biological systems. In this Account, we discuss the concept, development, key demonstrations, and future opportunities of mesh nanoelectronics as a general paradigm for seamless integration of electronics within synthetic tissues and live animals. We first describe the design and realization of hybrid synthetic tissues that are innervated in three dimensions (3D) with mesh nanoelectronics where the mesh serves as both as a tissue scaffold and as a platform of addressable electronic devices for monitoring and manipulating tissue behavior. Specific examples of tissue/nanoelectronic mesh hybrids highlighted include 3D neural tissue, cardiac patches, and vascular constructs, where the nanoelectronic devices have been used to carry out real-time 3D recording of electrophysiological and chemical signals in the tissues. This novel platform was also exploited for time-dependent 3D spatiotemporal mapping of cardiac tissue action potentials during cell culture and tissue maturation as well as in response to injection of pharmacological agents. The extension to simultaneous real-time monitoring and active control of tissue behavior is further discussed for multifunctional mesh nanoelectronics incorporating both recording and stimulation devices, providing the unique capability of bidirectional interfaces to cardiac tissue. In the case of live animals, new challenges must be addressed, including minimally invasive implantation, absence of deleterious chronic tissue response, and long-term capability for monitoring and modulating tissue activity. We discuss each of these topics in the context of implantation of mesh nanoelectronics into rodent brains. First, we describe the design of ultraflexible mesh nanoelectronics with size features and mechanical properties similar to brain tissue and a novel syringe-injection methodology that allows the mesh nanoelectronics to be precisely delivered to targeted brain regions in a minimally invasive manner. Next, we discuss time-dependent histology studies showing seamless and stable integration of mesh nanoelectronics within brain tissue on at least one year scales without evidence of chronic immune response or glial scarring characteristic of conventional implants. Third, armed with facile input/output interfaces, we describe multiplexed single-unit recordings that demonstrate stable tracking of the same individual neurons and local neural circuits for at least 8 months, long-term monitoring and stimulation of the same groups of neurons, and following changes in individual neuron activity during brain aging. Moving forward, we foresee substantial opportunities for (1) continued development of mesh nanoelectronics through, for example, broadening nanodevice signal detection modalities and taking advantage of tissue-like properties for selective cell targeting and (2) exploiting the unique capabilities of mesh nanoelectronics for tackling critical scientific and medical challenges such as understanding and potentially ameliorating cell and circuit level changes associated with natural and pathological aging, as well as using mesh nanoelectronics as active tissue scaffolds for regenerative medicine and as neuroprosthetics for monitoring and treating neurological diseases.

    View details for DOI 10.1021/acs.accounts.7b00547

    View details for Web of Science ID 000426014500013

    View details for PubMedID 29381054

    View details for PubMedCentralID PMC5820158

  • Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Fu, T., Hong, G., Viveros, R. D., Zhou, T., Lieber, C. M. 2017; 114 (47): E10046–E10055


    Implantable electrical probes have led to advances in neuroscience, brain-machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution of these neurons over the entire course of study. Silicon probes based on microfabrication can yield large-scale, high-density recording but face challenges of chronic gliosis and instability due to mechanical and structural mismatch with the brain. Ultraflexible mesh electronics, on the other hand, have demonstrated negligible chronic immune response and stable long-term brain monitoring at single-neuron level, although, to date, it has been limited to 16 channels. Here, we present a scalable scheme for highly multiplexed mesh electronics probes to bridge the gap between scalability and flexibility, where 32 to 128 channels per probe were implemented while the crucial brain-like structure and mechanics were maintained. Combining this mesh design with multisite injection, we demonstrate stable 128-channel local field potential and single-unit recordings from multiple brain regions in awake restrained mice over 4 mo. In addition, the newly integrated mesh is used to validate stable chronic recordings in freely behaving mice. This scalable scheme for mesh electronics together with demonstrated long-term stability represent important progress toward the realization of ideal implantable electrical probes allowing for mapping and tracking single-neuron level circuit changes associated with learning, aging, and neurodegenerative diseases.

    View details for DOI 10.1073/pnas.1717695114

    View details for Web of Science ID 000416503700008

    View details for PubMedID 29109247

    View details for PubMedCentralID PMC5703340

  • Syringe-Injectable Electronics with a Plug-and-Play Input/Output Interface NANO LETTERS Schuhmann, T. G., Yao, J., Hong, G., Fu, T., Lieber, C. M. 2017; 17 (9): 5836–42


    Syringe-injectable mesh electronics represent a new paradigm for brain science and neural prosthetics by virtue of the stable seamless integration of the electronics with neural tissues, a consequence of the macroporous mesh electronics structure with all size features similar to or less than individual neurons and tissue-like flexibility. These same properties, however, make input/output (I/O) connection to measurement electronics challenging, and work to-date has required methods that could be difficult to implement by the life sciences community. Here we present a new syringe-injectable mesh electronics design with plug-and-play I/O interfacing that is rapid, scalable, and user-friendly to nonexperts. The basic design tapers the ultraflexible mesh electronics to a narrow stem that routes all of the device/electrode interconnects to I/O pads that are inserted into a standard zero insertion force (ZIF) connector. Studies show that the entire plug-and-play mesh electronics can be delivered through capillary needles with precise targeting using microliter-scale injection volumes similar to the standard mesh electronics design. Electrical characterization of mesh electronics containing platinum (Pt) electrodes and silicon (Si) nanowire field-effect transistors (NW-FETs) demonstrates the ability to interface arbitrary devices with a contact resistance of only 3 Ω. Finally, in vivo injection into mice required only minutes for I/O connection and yielded expected local field potential (LFP) recordings from a compact head-stage compatible with chronic studies. Our results substantially lower barriers for use by new investigators and open the door for increasingly sophisticated and multifunctional mesh electronics designs for both basic and translational studies.

    View details for DOI 10.1021/acs.nanolett.7b03081

    View details for Web of Science ID 000411043500097

    View details for PubMedID 28787578

  • Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Zhou, T., Hong, G., Fu, T., Yang, X., Schuhmann, T. G., Viveros, R. D., Lieber, C. M. 2017; 114 (23): 5894–99


    Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2-12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.

    View details for DOI 10.1073/pnas.1705509114

    View details for Web of Science ID 000402703800043

    View details for PubMedID 28533392

    View details for PubMedCentralID PMC5468665

  • Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore CHEMICAL SCIENCE Feng, Y., Zhu, S., Antaris, A. L., Chen, H., Xiao, Y., Lu, X., Jiang, L., Diao, S., Yu, K., Wang, Y., Herraiz, S., Yue, J., Hong, X., Hong, G., Cheng, Z., Dai, H., Hsueh, A. J. 2017; 8 (5): 3703-3711


    In vivo imaging of hormone receptors provides the opportunity to visualize target tissues under hormonal control in live animals. Detecting longer-wavelength photons in the second near-infrared window (NIR-II, 1000-1700 nm) region affords reduced photon scattering in tissues accompanied by lower autofluorescence, leading to higher spatial resolution at up to centimeter tissue penetration depths. Here, we report the conjugation of a small molecular NIR-II fluorophore CH1055 to a follicle stimulating hormone (FSH-CH) for imaging ovaries and testes in live mice. After exposure to FSH-CH, specific NIR-II signals were found in cultured ovarian granulosa cells containing FSH receptors. Injection of FSH-CH allowed live imaging of ovarian follicles and testicular seminiferous tubules in female and male adult mice, respectively. Using prepubertal mice, NIR-II signals were detected in ovaries containing only preantral follicles. Resolving earlier controversies regarding the expression of FSH receptors in cultured osteoclasts, we detected for the first time specific FSH receptor signals in bones in vivo. The present imaging of FSH receptors in live animals using a ligand-conjugated NIR-II fluorophore with low cell toxicity and rapid clearance allows the development of non-invasive molecular imaging of diverse hormonal target cells in vivo.

    View details for DOI 10.1039/c6sc04897h

    View details for Web of Science ID 000400553000048

    View details for PubMedCentralID PMC5465568

  • Molecular imaging of biological systems with a clickable dye in the broad 800-to 1,700-nm near-infrared window PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Zhu, S., Yang, Q., Antaris, A. L., Yue, J., Ma, Z., Wang, H., Huang, W., Wan, H., Wang, J., Diao, S., Zhang, B., Li, X., Zhong, Y., Yu, K., Hong, G., Luo, J., Liang, Y., Dai, H. 2017; 114 (5): 962-967


    Fluorescence imaging multiplicity of biological systems is an area of intense focus, currently limited to fluorescence channels in the visible and first near-infrared (NIR-I; ∼700-900 nm) spectral regions. The development of conjugatable fluorophores with longer wavelength emission is highly desired to afford more targeting channels, reduce background autofluorescence, and achieve deeper tissue imaging depths. We have developed NIR-II (1,000-1,700 nm) molecular imaging agents with a bright NIR-II fluorophore through high-efficiency click chemistry to specific molecular antibodies. Relying on buoyant density differences during density gradient ultracentrifugation separations, highly pure NIR-II fluorophore-antibody conjugates emitting ∼1,100 nm were obtained for use as molecular-specific NIR-II probes. This facilitated 3D staining of ∼170-μm histological brain tissues sections on a home-built confocal microscope, demonstrating multicolor molecular imaging across both the NIR-I and NIR-II windows (800-1,700 nm).

    View details for DOI 10.1073/pnas.1617990114

    View details for PubMedID 28096386

  • Near-infrared fluorophores for biomedical imaging NATURE BIOMEDICAL ENGINEERING Hong, G., Antaris, A. L., Dai, H. 2017; 1 (1)
  • Stable long-term chronic brain mapping at the single-neuron level NATURE METHODS Fu, T., Hong, G., Zhou, T., Schuhmann, T. G., Viveros, R. D., Lieber, C. M. 2016; 13 (10): 875-+


    Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

    View details for DOI 10.1038/nmeth.3969

    View details for Web of Science ID 000385194600026

    View details for PubMedID 27571550

  • Traumatic Brain Injury Imaging in the Second Near-Infrared Window with a Molecular Fluorophore. Advanced materials Zhang, X., Wang, H., Antaris, A. L., Li, L., Diao, S., Ma, R., Nguyen, A., Hong, G., Ma, Z., Wang, J., Zhu, S., Castellano, J. M., Wyss-Coray, T., Liang, Y., Luo, J., Dai, H. 2016; 28 (32): 6872-6879


    Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. A bright, renal-excreted, and biocompatible near-infrared II fluorophore for in vivo imaging of TBI is designed. A transient hypoperfusion in the injured cerebral region, followed by fluorophore leakage, is observed. NIR-II fluorophores can provide noninvasive assessment of TBI.

    View details for DOI 10.1002/adma.201600706

    View details for PubMedID 27253071

  • IN VIVO VASCULAR IMAGING OF TRAUMATIC BRAIN INJURY IN THE SECOND NEAR-INFRARED WINDOW Zhang, X., Wang, H., Antaris, A., Li, L., Diao, S., Ma, R., Nguyen, A., Hong, G., Ma, Z., Wang, J., Zhu, S., Castellano, J., Wyss-Coray, T., Liang, Y., Luo, J., Dai, H. MARY ANN LIEBERT, INC. 2016: A48
  • A small-molecule dye for NIR-II imaging NATURE MATERIALS Antaris, A. L., Chen, H., Cheng, K., Sun, Y., Hong, G., Qu, C., Diao, S., Deng, Z., Hu, X., Zhang, B., Zhang, X., Yaghi, O. K., Alamparambil, Z. R., Hong, X., Cheng, Z., Dai, H. 2016; 15 (2): 235-?


    Fluorescent imaging of biological systems in the second near-infrared window (NIR-II) can probe tissue at centimetre depths and achieve micrometre-scale resolution at depths of millimetres. Unfortunately, all current NIR-II fluorophores are excreted slowly and are largely retained within the reticuloendothelial system, making clinical translation nearly impossible. Here, we report a rapidly excreted NIR-II fluorophore (∼90% excreted through the kidneys within 24 h) based on a synthetic 970-Da organic molecule (CH1055). The fluorophore outperformed indocyanine green (ICG)-a clinically approved NIR-I dye-in resolving mouse lymphatic vasculature and sentinel lymphatic mapping near a tumour. High levels of uptake of PEGylated-CH1055 dye were observed in brain tumours in mice, suggesting that the dye was detected at a depth of ∼4 mm. The CH1055 dye also allowed targeted molecular imaging of tumours in vivo when conjugated with anti-EGFR Affibody. Moreover, a superior tumour-to-background signal ratio allowed precise image-guided tumour-removal surgery.

    View details for DOI 10.1038/NMAT4476

    View details for Web of Science ID 000368766100030

  • Dispersion of High-Purity Semiconducting Arc-Discharged Carbon Nanotubes Using Backbone Engineered Diketopyrrolopyrrole (DPP)-Based Polymers ADVANCED ELECTRONIC MATERIALS Lei, T., Pitner, G., Chen, X., Hong, G., Park, S., Hayoz, P., Weitz, R. T., Wong, H. P., Bao, Z. 2016; 2 (1)
  • In Vivo Fluorescence Imaging in the Second Near-Infrared Window Using Carbon Nanotubes IN VIVO FLUORESCENCE IMAGING: METHODS AND PROTOCOLS Hong, G., Dai, H., Bai, M. 2016; 1444: 167–81


    In vivo fluorescence imaging in the second near-infrared window (NIR-II window, 1000-1700 nm) is a powerful imaging technique that emerged in recent years. This imaging tool allows for noninvasive, deep-tissue visualization and interrogation of anatomical features and functions with improved imaging resolution and contrast at greater tissue penetration depths than traditional fluorescence imaging. Here, we present the detailed protocol for conducting NIR-II fluorescence imaging in live animals, including the procedures for preparation of biocompatible and NIR-II fluorescent carbon nanotube solution, live animal administration and NIR-II fluorescence image acquisition.

    View details for PubMedID 27283426

  • Single Chirality (6,4) Single-Walled Carbon Nanotubes for Fluorescence Imaging with Silicon Detectors SMALL Antaris, A. L., Yaghi, O. K., Hong, G., Diao, S., Zhang, B., Yang, J., Chew, L., Dai, H. 2015; 11 (47): 6325-6330


    Postsynthetic single-walled carbon nanotube (SWCNT) sorting methods such as density gradient ultracentrifugation, gel chromatography, and electrophoresis have all been inspired by established biochemistry separation techniques designed to separate subcellular components. Biochemistry separation techniques have been refined to the degree that parameters such as pH, salt concentration, and temperature are necessary for a successful separation, yet these conditions are only now being applied to SWCNT separation methodologies. Slight changes in pH produce radically different behaviors of SWCNTs inside a density gradient, allowing for the facile separation of ultrahigh purity (6,4) SWCNTs from as-synthesized carbon nanotubes. The (6,4) SWCNTs are novel fluorophores emitting below ≈900 nm and can be easily detected with conventional silicon-based charge-coupled device detectors without the need for specialized InGaAs cameras. The (6,4) SWCNTs are used to demonstrate their potential as a clinically relevant NIR-I fluorescence stain for the immunohistochemical staining of cells and cancer tissue sections displaying high endothelial growth factor receptor levels.

    View details for DOI 10.1002/smll.201501530

    View details for Web of Science ID 000367916600010

  • Fluorescence Imaging In Vivo at Wavelengths beyond 1500 nm ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Diao, S., Blackburn, J. L., Hong, G., Antaris, A. L., Chang, J., Wu, J. Z., Zhang, B., Cheng, K., Kuo, C. J., Dai, H. 2015; 54 (49): 14758-14762


    Compared to imaging in the visible and near-infrared regions below 900 nm, imaging in the second near-infrared window (NIR-II, 1000-1700 nm) is a promising method for deep-tissue high-resolution optical imaging in vivo mainly owing to the reduced scattering of photons traversing through biological tissues. Herein, semiconducting single-walled carbon nanotubes with large diameters were used for in vivo fluorescence imaging in the long-wavelength NIR region (1500-1700 nm, NIR-IIb). With this imaging agent, 3-4 μm wide capillary blood vessels at a depth of about 3 mm could be resolved. Meanwhile, the blood-flow speeds in multiple individual vessels could be mapped simultaneously. Furthermore, NIR-IIb tumor imaging of a live mouse was explored. NIR-IIb imaging can be generalized to a wide range of fluorophores emitting at up to 1700 nm for high-performance in vivo optical imaging.

    View details for DOI 10.1002/anie.201507473

    View details for Web of Science ID 000367723400025

  • Carbon Nanomaterials for Biological Imaging and Nanomedicinal Therapy CHEMICAL REVIEWS Hong, G., Diao, S., Antaris, A. L., Dai, H. 2015; 115 (19): 10816-10906

    View details for DOI 10.1021/acs.chemrev.5b00008

    View details for Web of Science ID 000363002300009

    View details for PubMedID 25997028

  • Syringe Injectable Electronics: Precise Targeted Delivery with Quantitative Input/Output Connectivity NANO LETTERS Hong, G., Fu, T., Zhou, T., Schuhmann, T. G., Huang, J., Lieber, C. M. 2015; 15 (10): 6979–84


    Syringe-injectable mesh electronics with tissue-like mechanical properties and open macroporous structures is an emerging powerful paradigm for mapping and modulating brain activity. Indeed, the ultraflexible macroporous structure has exhibited unprecedented minimal/noninvasiveness and the promotion of attractive interactions with neurons in chronic studies. These same structural features also pose new challenges and opportunities for precise targeted delivery in specific brain regions and quantitative input/output (I/O) connectivity needed for reliable electrical measurements. Here, we describe new results that address in a flexible manner both of these points. First, we have developed a controlled injection approach that maintains the extended mesh structure during the "blind" injection process, while also achieving targeted delivery with ca. 20 μm spatial precision. Optical and microcomputed tomography results from injections into tissue-like hydrogel, ex vivo brain tissue, and in vivo brains validate our basic approach and demonstrate its generality. Second, we present a general strategy to achieve up to 100% multichannel I/O connectivity using an automated conductive ink printing methodology to connect the mesh electronics and a flexible flat cable, which serves as the standard "plug-in" interface to measurement electronics. Studies of resistance versus printed line width were used to identify optimal conditions, and moreover, frequency-dependent noise measurements show that the flexible printing process yields values comparable to commercial flip-chip bonding technology. Our results address two key challenges faced by syringe-injectable electronics and thereby pave the way for facile in vivo applications of injectable mesh electronics as a general and powerful tool for long-term mapping and modulation of brain activity in fundamental neuroscience through therapeutic biomedical studies.

    View details for DOI 10.1021/acs.nanolett.5b02987

    View details for Web of Science ID 000363003100105

    View details for PubMedID 26317328

  • Biological imaging without autofluorescence in the second near-infrared region NANO RESEARCH Diao, S., Hong, G., Antaris, A. L., Blackburn, J. L., Cheng, K., Cheng, Z., Dai, H. 2015; 8 (9): 3027-3034
  • Diketopyrrolopyrrole-Based Semiconducting Polymer Nanoparticles for In Vivo Photoacoustic Imaging. Advanced materials Pu, K., Mei, J., Jokerst, J. V., Hong, G., Antaris, A. L., Chattopadhyay, N., Shuhendler, A. J., Kurosawa, T., Zhou, Y., Gambhir, S. S., Bao, Z., Rao, J. 2015; 27 (35): 5184-5190


    Diketopyrrolopyrrole-based semiconducting polymer nanoparticles with high photostability and strong photoacoustic brightness are designed and synthesized, which results in 5.3-fold photoacoustic signal enhancement in tumor xenografts after systemic administration.

    View details for DOI 10.1002/adma.201502285

    View details for PubMedID 26247171

    View details for PubMedCentralID PMC4567488

  • Aligned-Braided Nanofibrillar Scaffold with Endothelial Cells Enhances Arteriogenesis ACS NANO Nakayarna, K. H., Hong, G., Lee, J. C., Patel, J., Edwards, B., Zaitseva, T. S., Paukshto, M. V., Dai, H., Cooke, J. P., Woo, Y. J., Huang, N. F. 2015; 9 (7): 6900-6908


    The objective of this study was to enhance the angiogenic capacity of endothelial cells (ECs) using nanoscale signaling cues from aligned nanofibrillar scaffolds in the setting of tissue ischemia. Thread-like nanofibrillar scaffolds with porous structure were fabricated from aligned-braided membranes generated under shear from liquid crystal collagen solution. Human ECs showed greater outgrowth from aligned scaffolds than from nonpatterned scaffolds. Integrin α1 was in part responsible for the enhanced cellular outgrowth on aligned nanofibrillar scaffolds, as the effect was abrogated by integrin α1 inhibition. To test the efficacy of EC-seeded aligned nanofibrillar scaffolds in improving neovascularization in vivo, the ischemic limbs of mice were treated with EC-seeded aligned nanofibrillar scaffold; EC-seeded nonpatterned scaffold; ECs in saline; aligned nanofibrillar scaffold alone; or no treatment. After 14 days, laser Doppler blood spectroscopy demonstrated significant improvement in blood perfusion recovery when treated with EC-seeded aligned nanofibrillar scaffolds, in comparison to ECs in saline or no treatment. In ischemic hindlimbs treated with scaffolds seeded with human ECs derived from induced pluripotent stem cells (iPSC-ECs), single-walled carbon nanotube (SWNT) fluorophores were systemically delivered to quantify microvascular density after 28 days. Near infrared-II (NIR-II, 1000-1700 nm) imaging of SWNT fluorophores demonstrated that iPSC-EC-seeded aligned scaffolds group showed significantly higher microvascular density than the saline or cells groups. These data suggest that treatment with EC-seeded aligned nanofibrillar scaffolds improved blood perfusion and arteriogenesis, when compared to treatment with cells alone or scaffold alone, and have important implications in the design of therapeutic cell delivery strategies.

    View details for DOI 10.1021/acsnano.5b00545

    View details for Web of Science ID 000358823200027

  • Syringe-injectable electronics NATURE NANOTECHNOLOGY Liu, J., Fu, T., Cheng, Z., Hong, G., Zhou, T., Jin, L., Duvvuri, M., Jiang, Z., Kruskal, P., Xie, C., Suo, Z., Fang, Y., Lieber, C. M. 2015; 10 (7): 629-+


    Seamless and minimally invasive three-dimensional interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and manipulation of their properties. Flexible electronics provide a means for conforming electronics to non-planar surfaces, yet targeted delivery of flexible electronics to internal regions remains difficult. Here, we overcome this challenge by demonstrating the syringe injection (and subsequent unfolding) of sub-micrometre-thick, centimetre-scale macroporous mesh electronics through needles with a diameter as small as 100 μm. Our results show that electronic components can be injected into man-made and biological cavities, as well as dense gels and tissue, with >90% device yield. We demonstrate several applications of syringe-injectable electronics as a general approach for interpenetrating flexible electronics with three-dimensional structures, including (1) monitoring internal mechanical strains in polymer cavities, (2) tight integration and low chronic immunoreactivity with several distinct regions of the brain, and (3) in vivo multiplexed neural recording. Moreover, syringe injection enables the delivery of flexible electronics through a rigid shell, the delivery of large-volume flexible electronics that can fill internal cavities, and co-injection of electronics with other materials into host structures, opening up unique applications for flexible electronics.

    View details for DOI 10.1038/NNANO.2015.115

    View details for Web of Science ID 000357485600019

    View details for PubMedID 26053995

    View details for PubMedCentralID PMC4591029

  • Diketopyrrolopyrrole (DPP)-Based Donor-Acceptor Polymers for Selective Dispersion of Large-Diameter Semiconducting Carbon Nanotubes SMALL Lei, T., Lai, Y., Hong, G., Wang, H., Hayoz, P., Weitz, R. T., Chen, C., Dai, H., Bao, Z. 2015; 11 (24): 2946-2954


    Low-bandgap diketopyrrolopyrrole (DPP)-based polymers are used for the selective dispersion of semiconducting single-walled carbon nanotubes (s-SWCNTs). Through rational molecular design to tune the polymer-SWCNT interactions, highly selective dispersions of s-SWCNTs with diameters mainly around 1.5 nm are achieved. The influences of the polymer alkyl side-chain substitution (i.e., branched vs linear side chains) on the dispersing yield and selectivity of s-SWCNTs are investigated. Introducing linear alkyl side chains allows increased polymer-SWCNT interactions through close π-π stacking and improved C-H-π interactions. This work demonstrates that polymer side-chain engineering is an effective method to modulate the polymer-SWCNT interactions and thereby affecting both critical parameters in dispersing yield and selectivity. Using these sorted s-SWCNTs, high-performance SWCNT network thin-film transistors are fabricated. The solution-deposited s-SWCNT transistors yield simultaneously high mobilities of 41.2 cm(2) V(-1) s(-1) and high on/off ratios of greater than 10(4) . In summary, low-bandgap DPP donor-acceptor polymers are a promising class of polymers for selective dispersion of large-diameter s-SWCNTs.

    View details for DOI 10.1002/smll.201403761

    View details for PubMedID 25711378

  • General Strategy for Biodetection in High Ionic Strength Solutions Using Transistor-Based Nanoelectronic Sensors NANO LETTERS Gao, N., Zhou, W., Jiang, X., Hong, G., Fu, T., Lieber, C. M. 2015; 15 (3): 2143–48


    Transistor-based nanoelectronic sensors are capable of label-free real-time chemical and biological detection with high sensitivity and spatial resolution, although the short Debye screening length in high ionic strength solutions has made difficult applications relevant to physiological conditions. Here, we describe a new and general strategy to overcome this challenge for field-effect transistor (FET) sensors that involves incorporating a porous and biomolecule permeable polymer layer on the FET sensor. This polymer layer increases the effective screening length in the region immediately adjacent to the device surface and thereby enables detection of biomolecules in high ionic strength solutions in real-time. Studies of silicon nanowire field-effect transistors with additional polyethylene glycol (PEG) modification show that prostate specific antigen (PSA) can be readily detected in solutions with phosphate buffer (PB) concentrations as high as 150 mM, while similar devices without PEG modification only exhibit detectable signals for concentrations ≤10 mM. Concentration-dependent measurements exhibited real-time detection of PSA with a sensitivity of at least 10 nM in 100 mM PB with linear response up to the highest (1000 nM) PSA concentrations tested. The current work represents an important step toward general application of transistor-based nanoelectronic detectors for biochemical sensing in physiological environments and is expected to open up exciting opportunities for in vitro and in vivo biological sensing relevant to basic biology research through medicine.

    View details for DOI 10.1021/acs.nanolett.5b00133

    View details for Web of Science ID 000351188000107

    View details for PubMedID 25664395

    View details for PubMedCentralID PMC4594804

  • Graphene nanoribbons under mechanical strain. Advanced materials Chen, C., Wu, J. Z., Lam, K. T., Hong, G., Gong, M., Zhang, B., Lu, Y., Antaris, A. L., Diao, S., Guo, J., Dai, H. 2015; 27 (2): 303-309


    Uniaxial strains are introduced into individual graphene nanoribbons (GNRs) with highly smooth edges to investigate the strain effects on Raman spectroscopic and electrical properties of GNRs. It is found that uniaxial strain downshifts the Raman G-band frequency of GNRs linearly and tunes their bandgap significantly in a non-monotonic manner. The strain engineering of GNRs is promising for potential electronics and photonics applications.

    View details for DOI 10.1002/adma.201403750

    View details for PubMedID 25355690

  • Through-skull fluorescence imaging of the brain in a new near-infrared window NATURE PHOTONICS Hong, G., Diao, S., Chang, J., Antaris, A. L., Chen, C., Zhang, B., Zhao, S., Atochin, D. N., Huang, P. L., Andreasson, K. I., Kuo, C. J., Dai, H. 2014; 8 (9): 723-730


    To date, brain imaging has largely relied on X-ray computed tomography and magnetic resonance angiography with limited spatial resolution and long scanning times. Fluorescence-based brain imaging in the visible and traditional near-infrared regions (400-900 nm) is an alternative but currently requires craniotomy, cranial windows and skull thinning techniques, and the penetration depth is limited to 1-2 mm due to light scattering. Here, we report through-scalp and through-skull fluorescence imaging of mouse cerebral vasculature without craniotomy utilizing the intrinsic photoluminescence of single-walled carbon nanotubes in the 1.3-1.4 micrometre near-infrared window. Reduced photon scattering in this spectral region allows fluorescence imaging reaching a depth of >2 mm in mouse brain with sub-10 micrometre resolution. An imaging rate of ~5.3 frames/s allows for dynamic recording of blood perfusion in the cerebral vessels with sufficient temporal resolution, providing real-time assessment of blood flow anomaly in a mouse middle cerebral artery occlusion stroke model.

    View details for DOI 10.1038/NPHOTON.2014.166

    View details for Web of Science ID 000342600100016

    View details for PubMedCentralID PMC5026222

  • Tumor Metastasis Inhibition by Imaging-Guided Photothermal Therapy with Single-Walled Carbon Nanotubes ADVANCED MATERIALS Liang, C., Diao, S., Wang, C., Gong, H., Liu, T., Hong, G., Shi, X., Dai, H., Liu, Z. 2014; 26 (32): 5646-?


    Multi-modal imaging guided photothermal therapy with single-walled carbon nanotubes affords effective destruction of primary tumors together with cancer cells in sentinel lymph nodes. This results in remarkably prolonged mouse survival compared to mice treated by elimination of only the primary tumor by either surgery or conventional photothermal therapy.

    View details for DOI 10.1002/adma.201401825

    View details for Web of Science ID 000340900800007

    View details for PubMedID 24924258

  • Diketopyrrolopyrrole (DPP)-based donor-acceptor polymers for scalable and selective dispersion of large-diameter carbon nanotubes Lei, T., Lai, Y., Hong, G., Wang, H., Dai, H., Bao, Z. AMER CHEMICAL SOC. 2014
  • Ultrafast fluorescence imaging in vivo with conjugated polymer fluorophores in the second near-infrared window NATURE COMMUNICATIONS Hong, G., Zou, Y., Antaris, A. L., Diao, S., Wu, D., Cheng, K., Zhang, X., Chen, C., Liu, B., He, Y., Wu, J. Z., Yuan, J., Zhang, B., Tao, Z., Fukunaga, C., Dai, H. 2014; 5


    In vivo fluorescence imaging in the second near-infrared window (1.0-1.7 μm) can afford deep tissue penetration and high spatial resolution, owing to the reduced scattering of long-wavelength photons. Here we synthesize a series of low-bandgap donor/acceptor copolymers with tunable emission wavelengths of 1,050-1,350 nm in this window. Non-covalent functionalization with phospholipid-polyethylene glycol results in water-soluble and biocompatible polymeric nanoparticles, allowing for live cell molecular imaging at >1,000 nm with polymer fluorophores for the first time. Importantly, the high quantum yield of the polymer allows for in vivo, deep-tissue and ultrafast imaging of mouse arterial blood flow with an unprecedented frame rate of >25 frames per second. The high time-resolution results in spatially and time resolved imaging of the blood flow pattern in cardiogram waveform over a single cardiac cycle (~200 ms) of a mouse, which has not been observed with fluorescence imaging in this window before.

    View details for DOI 10.1038/ncomms5206

    View details for Web of Science ID 000338839100002

  • Near-Infrared II Fluorescence for Imaging Hindlimb Vessel Regeneration With Dynamic Tissue Perfusion Measurement. Circulation. Cardiovascular imaging Hong, G., Lee, J. C., Jha, A., Diao, S., Nakayama, K. H., Hou, L., Doyle, T. C., Robinson, J. T., Antaris, A. L., Dai, H., Cooke, J. P., Huang, N. F. 2014; 7 (3): 517-525


    Real-time vascular imaging that provides both anatomic and hemodynamic information could greatly facilitate the diagnosis of vascular diseases and provide accurate assessment of therapeutic effects. Here, we have developed a novel fluorescence-based all-optical method, named near-infrared II (NIR-II) fluorescence imaging, to image murine hindlimb vasculature and blood flow in an experimental model of peripheral arterial disease, by exploiting fluorescence in the NIR-II region (1000-1400 nm) of photon wavelengths.Because of the reduced photon scattering of NIR-II fluorescence compared with traditional NIR fluorescence imaging and thus much deeper penetration depth into the body, we demonstrated that the mouse hindlimb vasculature could be imaged with higher spatial resolution than in vivo microscopic computed tomography. Furthermore, imaging during 26 days revealed a significant increase in hindlimb microvascular density in response to experimentally induced ischemia within the first 8 days of the surgery (P<0.005), which was confirmed by histological analysis of microvascular density. Moreover, the tissue perfusion in the ischemic hindlimb could be quantitatively measured by the dynamic NIR-II method, revealing the temporal kinetics of blood flow recovery that resembled microbead-based blood flowmetry and laser Doppler blood spectroscopy.The penetration depth of millimeters, high spatial resolution, and fast acquisition rate of NIR-II imaging make it a useful imaging tool for murine models of vascular disease.

    View details for DOI 10.1161/CIRCIMAGING.113.000305

    View details for PubMedID 24657826

  • Graphite Oxide Nanoparticles with Diameter Greater than 20 nm Are Biocompatible with Mouse Embryonic Stem Cells and Can Be Used in a Tissue Engineering System. Small Wang, I. E., Robinson, J. T., Do, G., Hong, G., Gould, D. R., Dai, H., Yang, P. C. 2014; 10 (8): 1479-1484


    Graphite oxide sheets demonstrate size-dependent uptake and toxicity towards embryonic stem cells. Graphite oxide sheets larger than 20 nm are biocompatible and can be safely used with mouse embryonic stem cells, while graphite oxide sheets smaller than 20 nm in diameter reduced cell proliferation and increased cell toxicity.

    View details for DOI 10.1002/smll.201303133

    View details for PubMedID 24376186

  • Plasmonic micro-beads for fluorescence enhanced, multiplexed protein detection with flow cytometry CHEMICAL SCIENCE Zhang, B., Yang, J., Zou, Y., Gong, M., Chen, H., Hong, G., Antaris, A. L., Li, X., Liu, C., Chen, C., Dai, H. 2014; 5 (10): 4070-4075

    View details for DOI 10.1039/c4sc01206b

    View details for Web of Science ID 000341195100048

  • Biological Imaging Using Nanoparticles of Small Organic Molecules with Fluorescence Emission at Wavelengths Longer than 1000 nm. Angewandte Chemie (International ed. in English) Tao, Z., Hong, G., Shinji, C., Chen, C., Diao, S., Antaris, A. L., Zhang, B., Zou, Y., Dai, H. 2013; 52 (49): 13002-13006


    Embedded in a polymer: A hydrophobic organic molecule that fluoresces in the near-infrared II (NIR-II) region was made water-soluble and biocompatible by its embedment in a polymer nanoparticle, which was then coated with hydrophilic poly(ethylene glycol) chains. The resulting nanoparticles exhibit bright fluorescence in the NIR-II window and high photostability in aqueous media and were used for in vivo imaging in mice.

    View details for DOI 10.1002/anie.201307346

    View details for PubMedID 24174264

  • Biodistribution, pharmacokinetics and toxicology of Ag2S near-infrared quantum dots in mice BIOMATERIALS Zhang, Y., Zhang, Y., Hong, G., He, W., Zhou, K., Yang, K., Li, F., Chen, G., Liu, Z., Dai, H., Wang, Q. 2013; 34 (14): 3639-3646


    Ag2S quantum dots (QDs) have been demonstrated as a promising near-infrared II (NIR-II, 1.0-1.4 μm) emitting nanoprobe for in vivo imaging and detection. In this work, we carefully study the long-term in vivo biodistribution of Ag2S QDs functionalized with polyethylene glycol (PEG) and systematically examine the potential toxicity of Ag2S QDs over time. Our results show that PEGylated-Ag2S QDs are mainly accumulated in the reticuloendothelial system (RES) including liver and spleen after intravenous administration and can be gradually cleared, mostly by fecal excretion. PEGylated-Ag2S QDs do not cause appreciable toxicity at our tested doses (15 and 30 mg/kg) to the treated mice over a period of 2 months as evidenced by blood biochemistry, hematological analysis and histological examinations. Our work lays a solid foundation for further biomedical applications of Ag2S QDs as an important in vivo imaging agent in the NIR-II region.

    View details for DOI 10.1016/j.biomaterials.2013.01.089

    View details for Web of Science ID 000317534200010

    View details for PubMedID 23415643

  • Ultra-Low Doses of Chirality Sorted (6,5) Carbon Nanotubes for Simultaneous Tumor Imaging and Photothermal Therapy ACS NANO Antaris, A. L., Robinson, J. T., Yaghi, O. K., Hong, G., Diao, S., Luong, R., Dai, H. 2013; 7 (4): 3644-3652


    Single-walled carbon nanotubes (SWCNTs) exhibit intrinsic fluorescence and strong optical absorption in the near-infrared (NIR) biological window (0.7-1.4 μm), rendering them ideal for in vivo imaging and photothermal therapy. Advances in SWCNT sorting have led to improved nanoelectronics and are promising for nanomedicine. To date, SWCNTs used in vivo consist of heterogeneous mixtures of nanotubes and only a small subset of chirality nanotubes fluoresces or heats under a NIR laser. Here, we demonstrate that separated (6,5) SWCNTs exchanged into a biocompatible surfactant, C18-PMH-mPEG, are more than 6-fold brighter in photoluminescence on the per mass basis, afford clear tumor imaging, and reach requisite photothermal tumor ablation temperatures with a >10-fold lower injected dose than as-synthesized SWCNT mixtures while exhibiting relatively low (6,5) accumulation in the reticuloendothelial system. The intravenous injection of ∼4 μg of (6,5) SWCNTs per mouse (0.254 mg/kg) for dual imaging/photothermal therapy is, by far, the lowest reported dose for nanoparticle-based in vivo therapeutics.

    View details for DOI 10.1021/nn4006472

    View details for Web of Science ID 000318143300081

    View details for PubMedID 23521224

  • Multiplexed cytokine detection on plasmonic gold substrates with enhanced near-infrared fluorescence NANO RESEARCH Zhang, B., Price, J., Hong, G., Tabakman, S. M., Wang, H., Jarrell, J. A., Feng, J., Utz, P. J., Dai, H. 2013; 6 (2): 113-120
  • An integrated Peptide-antigen microarray on plasmonic gold films for sensitive human antibody profiling. PloS one Zhang, B., Jarrell, J. A., Price, J. V., Tabakman, S. M., Li, Y., Gong, M., Hong, G., Feng, J., Utz, P. J., Dai, H. 2013; 8 (7): e71043


    High-throughput screening for interactions of peptides with a variety of antibody targets could greatly facilitate proteomic analysis for epitope mapping, enzyme profiling, drug discovery and biomarker identification. Peptide microarrays are suited for such undertaking because of their high-throughput capability. However, existing peptide microarrays lack the sensitivity needed for detecting low abundance proteins or low affinity peptide-protein interactions. This work presents a new peptide microarray platform constructed on nanostructured plasmonic gold substrates capable of metal enhanced NIR fluorescence enhancement (NIR-FE) by hundreds of folds for screening peptide-antibody interactions with ultrahigh sensitivity. Further, an integrated histone peptide and whole antigen array is developed on the same plasmonic gold chip for profiling human antibodies in the sera of systemic lupus erythematosus (SLE) patients, revealing that collectively a panel of biomarkers against unmodified and post-translationally modified histone peptides and several whole antigens allow more accurate differentiation of SLE patients from healthy individuals than profiling biomarkers against peptides or whole antigens alone.

    View details for DOI 10.1371/journal.pone.0071043

    View details for PubMedID 23923050

    View details for PubMedCentralID PMC3726620

  • Advanced zinc-air batteries based on high-performance hybrid electrocatalysts. Nature communications Li, Y., Gong, M., Liang, Y., Feng, J., Kim, J., Wang, H., Hong, G., Zhang, B., Dai, H. 2013; 4: 1805-?


    Primary and rechargeable Zn-air batteries could be ideal energy storage devices with high energy and power density, high safety and economic viability. Active and durable electrocatalysts on the cathode side are required to catalyse oxygen reduction reaction during discharge and oxygen evolution reaction during charge for rechargeable batteries. Here we developed advanced primary and rechargeable Zn-air batteries with novel CoO/carbon nanotube hybrid oxygen reduction catalyst and Ni-Fe-layered double hydroxide oxygen evolution catalyst for the cathode. These catalysts exhibited higher catalytic activity and durability in concentrated alkaline electrolytes than precious metal Pt and Ir catalysts. The resulting primary Zn-air battery showed high discharge peak power density ~265 mW cm(-2), current density ~200 mA cm(-2) at 1 V and energy density >700 Wh kg(-1). Rechargeable Zn-air batteries in a tri-electrode configuration exhibited an unprecedented small charge-discharge voltage polarization of ~0.70 V at 20 mA cm(-2), high reversibility and stability over long charge and discharge cycles.

    View details for DOI 10.1038/ncomms2812

    View details for PubMedID 23651993

  • Multifunctional in vivo vascular imaging using near-infrared II fluorescence NATURE MEDICINE Hong, G., Lee, J. C., Robinson, J. T., Raaz, U., Xie, L., Huang, N. F., Cooke, J. P., Dai, H. 2012; 18 (12): 1841-?


    In vivo real-time epifluorescence imaging of mouse hind limb vasculatures in the second near-infrared region (NIR-II) is performed using single-walled carbon nanotubes as fluorophores. Both high spatial (∼30 μm) and temporal (<200 ms per frame) resolution for small-vessel imaging are achieved at 1-3 mm deep in the hind limb owing to the beneficial NIR-II optical window that affords deep anatomical penetration and low scattering. This spatial resolution is unattainable by traditional NIR imaging (NIR-I) or microscopic computed tomography, and the temporal resolution far exceeds scanning microscopic imaging techniques. Arterial and venous vessels are unambiguously differentiated using a dynamic contrast-enhanced NIR-II imaging technique on the basis of their distinct hemodynamics. Further, the deep tissue penetration and high spatial and temporal resolution of NIR-II imaging allow for precise quantifications of blood velocity in both normal and ischemic femoral arteries, which are beyond the capabilities of ultrasonography at lower blood velocities.

    View details for DOI 10.1038/nm.2995

    View details for PubMedID 23160236

  • Chirality Enriched (12,1) and (11,3) Single-Walled Carbon Nanotubes for Biological Imaging JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Diao, S., Hong, G., Robinson, J. T., Jiao, L., Antaris, A. L., Wu, J. Z., Choi, C. L., Dai, H. 2012; 134 (41): 16971-16974


    The intrinsic band gap photoluminescence of semiconducting single-walled carbon nanotubes (SWNTs) makes them promising biological imaging probes in the second near-infrared (NIR-II, 1.0-1.4 μm) window. Thus far, SWNTs used for biological applications have been a complex mixture of metallic and semiconducting species with random chiralities, preventing simultaneous resonant excitation of all semiconducting nanotubes and emission at a single well-defined wavelength. Here, we developed a simple gel filtration method to enrich semiconducting (12,1) and (11,3) SWNTs with identical resonance absorption at ~808 nm and emission near ~1200 nm. The chirality sorted SWNTs showed ~5-fold higher photoluminescence intensity under resonant excitation of 808 nm than unsorted SWNTs on a per-mass basis. Real-time in vivo video imaging of whole mouse body and tumor vessels was achieved using a ~6-fold lower injected dose of (12,1) and (11,3) SWNTs (~3 μg per mouse or ~0.16 mg/kg of body weight vs 1.0 mg/kg for unsorted SWNTs) than a previous heterogeneous mixture, demonstrating the first resonantly excited and chirality separated SWNTs for biological imaging.

    View details for DOI 10.1021/ja307966u

    View details for Web of Science ID 000309854700014

    View details for PubMedID 23033937

  • Oxygen Reduction Electrocatalyst Based on Strongly Coupled Cobalt Oxide Nanocrystals and Carbon Nanotubes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Liang, Y., Wang, H., Diao, P., Chang, W., Hong, G., Li, Y., Gong, M., Xie, L., Zhou, J., Wang, J., Regier, T. Z., Wei, F., Dai, H. 2012; 134 (38): 15849-15857


    Electrocatalyst for oxygen reduction reaction (ORR) is crucial for a variety of renewable energy applications and energy-intensive industries. The design and synthesis of highly active ORR catalysts with strong durability at low cost is extremely desirable but remains challenging. Here, we used a simple two-step method to synthesize cobalt oxide/carbon nanotube (CNT) strongly coupled hybrid as efficient ORR catalyst by directly growing nanocrystals on oxidized multiwalled CNTs. The mildly oxidized CNTs provided functional groups on the outer walls to nucleate and anchor nanocrystals, while retaining intact inner walls for highly conducting network. Cobalt oxide was in the form of CoO due to a gas-phase annealing step in NH(3). The resulting CoO/nitrogen-doped CNT (NCNT) hybrid showed high ORR current density that outperformed Co(3)O(4)/graphene hybrid and commercial Pt/C catalyst at medium overpotential, mainly through a 4e reduction pathway. The metal oxide/carbon nanotube hybrid was found to be advantageous over the graphene counterpart in terms of active sites and charge transport. Last, the CoO/NCNT hybrid showed high ORR activity and stability under a highly corrosive condition of 10 M NaOH at 80 °C, demonstrating the potential of strongly coupled inorganic/nanocarbon hybrid as a novel catalyst system in oxygen depolarized cathode for chlor-alkali electrolysis.

    View details for DOI 10.1021/ja305623m

    View details for PubMedID 22957510

  • In Vivo Fluorescence Imaging in the Second Near-Infrared Window with Long Circulating Carbon Nanotubes Capable of Ultrahigh Tumor Uptake JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Robinson, J. T., Hong, G., Liang, Y., Zhang, B., Yaghi, O. K., Dai, H. 2012; 134 (25): 10664-10669


    Cancer imaging requires selective high accumulation of contrast agents in the tumor region and correspondingly low uptake in healthy tissues. Here, by making use of a novel synthetic polymer to solubilize single-walled carbon nanotubes (SWNTs), we prepared a well-functionalized SWNT formulation with long blood circulation (half-life of ∼30 h) in vivo to achieve ultrahigh accumulation of ∼30% injected dose (ID)/g in 4T1 murine breast tumors in Balb/c mice. Functionalization dependent blood circulation and tumor uptake were investigated through comparisons with phospholipid-PEG solubilized SWNTs. For the first time, we performed video-rate imaging of tumors based on the intrinsic fluorescence of SWNTs in the second near-infrared (NIR-II, 1.1-1.4 μm) window. We carried out dynamic contrast imaging through principal component analysis (PCA) to immediately pinpoint the tumor within ∼20 s after injection. Imaging over time revealed increasing tumor contrast up to 72 h after injection, allowing for its unambiguous identification. The 3D reconstruction of the SWNTs distribution based on their stable photoluminescence inside the tumor revealed a high degree of colocalization of SWNTs and blood vessels, suggesting enhanced permeability and retention (EPR) effect as the main cause of high passive tumor uptake of the nanotubes.

    View details for DOI 10.1021/ja303737a

    View details for Web of Science ID 000305716700052

    View details for PubMedID 22667448

    View details for PubMedCentralID PMC3471786

  • Short channel field-effect transistors from highly enriched semiconducting carbon nanotubes NANO RESEARCH Wu, J., Xie, L., Hong, G., Lim, H. E., Thendie, B., Miyata, Y., Shinohara, H., Dai, H. 2012; 5 (6): 388-394
  • Ag2S Quantum Dot: A Bright and Biocompatible Fluorescent Nanoprobe in the Second Near-Infrared Window ACS NANO Zhang, Y., Hong, G., Zhang, Y., Chen, G., Li, F., Dai, H., Wang, Q. 2012; 6 (5): 3695-3702


    Ag(2)S quantum dots (QDs) emitting in the second near-infrared region (NIR-II, 1.0-1.4 μm) are demonstrated as a promising fluorescent probe with both bright photoluminescence and high biocompatibility for the first time. Highly selective in vitro targeting and imaging of different cell lines are achieved using biocompatible NIR-II Ag(2)S QDs with different targeting ligands. The cytotoxicity study illustrates the Ag(2)S QDs with negligible effects in altering cell proliferation, triggering apoptosis and necrosis, generating reactive oxygen species, and causing DNA damage. Our results have opened up the possibilities of using these biocompatible Ag(2)S QDs for in vivo anatomical imaging and early stage tumor diagnosis with deep tissue penetration, high sensitivity, and elevated spatial and temporal resolution owing to their high emission efficiency in the unique NIR-II imaging window.

    View details for DOI 10.1021/nn301218z

    View details for Web of Science ID 000304231700007

    View details for PubMedID 22515909

    View details for PubMedCentralID PMC3358570

  • Three-dimensional imaging of single nanotube molecule endocytosis on plasmonic substrates NATURE COMMUNICATIONS Hong, G., Wu, J. Z., Robinson, J. T., Wang, H., Zhang, B., Dai, H. 2012; 3


    Investigating the cellular internalization pathways of single molecules or single nano objects is important to understanding cell-matter interactions, and to applications in drug delivery and discovery. Imaging and tracking the motion of single molecules on cell plasma membranes require high spatial resolution in three dimensions. Fluorescence imaging along the axial dimension with nanometre resolution has been highly challenging, but critical to revealing displacements in transmembrane events. Here, utilizing a plasmonic ruler based on the sensitive distance dependence of near-infrared fluorescence enhancement of carbon nanotubes on a gold plasmonic substrate, we probe ~10 nm scale transmembrane displacements through changes in nanotube fluorescence intensity, enabling observations of single nanotube endocytosis in three dimensions. Cellular uptake and transmembrane displacements show clear dependences to temperature and clathrin assembly on cell membrane, suggesting that the cellular entry mechanism for a nanotube molecule is via clathrin-dependent endocytosis through the formation of clathrin-coated pits on the cell membrane.

    View details for DOI 10.1038/ncomms1698

    View details for PubMedID 22426221

  • Graphite-Coated Magnetic Nanoparticle Microarray for Few-Cells Enrichment and Detection ACS NANO Chen, Z., Hong, G., Wang, H., Welsher, K., Tabakman, S. M., Sherlock, S. P., Robinson, J. T., Liang, Y., Dai, H. 2012; 6 (2): 1094-1101


    Graphite-coated, highly magnetic FeCo core-shell nanoparticles were synthesized by a chemical vapor deposition method and solubilized in aqueous solution through a unique polymer mixture modification, which significantly improved the biocompatibility and stability of the magnetic nanoparticles (MNPs). Such functionalized MNPs were proven to be very stable in different conditions which would be significant for biological applications. Cell staining, manipulation, enrichment, and detection were developed with these MNPs. Under external magnetic manipulation, the MNP-stained cells exhibited directed motions. Moreover, MNPs were printed on substrates to modulate the magnetic field distribution on the surface. Capture and detection of sparse populations of cancer cells spiked into whole blood has been explored in a microarray fashion. Cancer cells from hundreds down to only two were able to be simply and efficiently detected from 1 mL of whole blood on the MNP microarray chips. Interestingly, the cells captured through the MNP microarray still showed viability and adhered to the MNP spots after incubation, which could be utilized for cancer cell detection, localized growth, and proliferation.

    View details for DOI 10.1021/nn2034692

    View details for Web of Science ID 000300757900013

    View details for PubMedID 22229344

  • In Vivo Fluorescence Imaging with Ag2S Quantum Dots in the Second Near-Infrared Region ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Hong, G., Robinson, J. T., Zhang, Y., Diao, S., Antaris, A. L., Wang, Q., Dai, H. 2012; 51 (39): 9818-9821


    Hits the dot: Ag(2)S quantum dots (QDs) with bright near-infrared-II fluorescence emission (around 1200 nm) and six-arm branched PEG surface coating were synthesized for in vivo small-animal imaging. The 6PEG-Ag(2)S QDs afforded a tumor uptake of approximately 10 % injected dose/gram, owing to a long circulation half-life of approximately 4 h. Clearance of the injected 6PEG-Ag(2)S QDs occurs mainly through the biliary pathway in mice.

    View details for DOI 10.1002/anie.201206059

    View details for Web of Science ID 000308886800018

    View details for PubMedID 22951900

  • Metal enhanced fluorescence of carbon nanotubes: Observation and application in enhanced cell imaging 242nd National Meeting of the American-Chemical-Society (ACS) Hong, G. AMER CHEMICAL SOC. 2011
  • MoS2 Nanoparticles Grown on Graphene: An Advanced Catalyst for the Hydrogen Evolution Reaction JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Li, Y., Wang, H., Xie, L., Liang, Y., Hong, G., Dai, H. 2011; 133 (19): 7296-7299


    Advanced materials for electrocatalytic and photoelectrochemical water splitting are central to the area of renewable energy. In this work, we developed a selective solvothermal synthesis of MoS(2) nanoparticles on reduced graphene oxide (RGO) sheets suspended in solution. The resulting MoS(2)/RGO hybrid material possessed nanoscopic few-layer MoS(2) structures with an abundance of exposed edges stacked onto graphene, in strong contrast to large aggregated MoS(2) particles grown freely in solution without GO. The MoS(2)/RGO hybrid exhibited superior electrocatalytic activity in the hydrogen evolution reaction (HER) relative to other MoS(2) catalysts. A Tafel slope of ∼41 mV/decade was measured for MoS(2) catalysts in the HER for the first time; this exceeds by far the activity of previous MoS(2) catalysts and results from the abundance of catalytic edge sites on the MoS(2) nanoparticles and the excellent electrical coupling to the underlying graphene network. The ∼41 mV/decade Tafel slope suggested the Volmer-Heyrovsky mechanism for the MoS(2)-catalyzed HER, with electrochemical desorption of hydrogen as the rate-limiting step.

    View details for DOI 10.1021/ja201269b

    View details for PubMedID 21510646

  • Near-Infrared-Fluorescence-Enhanced Molecular Imaging of Live Cells on Gold Substrates ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Hong, G., Tabakman, S. M., Welsher, K., Chen, Z., Robinson, J. T., Wang, H., Zhang, B., Dai, H. 2011; 50 (20): 4644-4648

    View details for DOI 10.1002/anie.201100934

    View details for PubMedID 21506225

  • Biomimetic morphogenesis of micropottery: helical coiling of mesostructured silica nanofibers SOFT MATTER Zhou, L., Ye, J., Hong, G., Qi, L. 2011; 7 (20): 9624–27

    View details for DOI 10.1039/c1sm05593c

    View details for Web of Science ID 000295582000011

  • LiMn1-xFexPO4 Nanorods Grown on Graphene Sheets for Ultrahigh-Rate-Performance Lithium Ion Batteries ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Wang, H., Yang, Y., Liang, Y., Cui, L., Casalongue, H. S., Li, Y., Hong, G., Cui, Y., Dai, H. 2011; 50 (32): 7364-7368

    View details for DOI 10.1002/anie.201103163

    View details for PubMedID 21710671

  • Optical Properties of Single-Walled Carbon Nanotubes Separated in a Density Gradient: Length, Bundling, and Aromatic Stacking Effects JOURNAL OF PHYSICAL CHEMISTRY C Tabakman, S. M., Welsher, K., Hong, G., Dai, H. 2010; 114 (46): 19569-19575


    Single-walled carbon nanotubes (SWNTs) are promising materials for in vitro and in vivo biological applications due to their high surface area and inherent near infrared photoluminescence and Raman scattering properties. Here, we use density gradient centrifugation to separate SWNTs by length and degree of bundling. Following separation, we observe a peak in photoluminescence quantum yield (PL QY) and Raman scattering intensity where SWNT length is maximized and bundling is minimized. Individualized SWNTs are found to exhibit high PL QY and high resonance-enhanced Raman scattering intensity. Fractions containing long, individual SWNTs exhibit the highest PL QY and Raman scattering intensities, compared to fractions containing single, short SWNTs or SWNT bundles. Intensity gains of approximately ~1.7 and 4-fold, respectively, are obtained compared with the starting material. Spectroscopic analysis reveals that SWNT fractions at higher displacement contain increasing proportions of SWNT bundles, which causes reduced optical transition energies and broadening of absorption features in the UV-Vis-NIR spectra, and reduced PL QY and Raman scattering intensity. Finally, we adsorb small aromatic species on "bright," individualized SWNT sidewalls and compare the resulting absorption, PL and Raman scattering effects to that of SWNT bundles. We observe similar effects in both cases, suggesting aromatic stacking affects the optical properties of SWNTs in an analogous way to SWNT bundles, likely due to electronic structure perturbations, charge transfer, and dielectric screening effects, resulting in reduction of the excitonic optical transition energies and exciton lifetimes.

    View details for DOI 10.1021/jp106453v

    View details for Web of Science ID 000284287900003

    View details for PubMedCentralID PMC3023917

  • Metal-Enhanced Fluorescence of Carbon Nanotubes JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Hong, G., Tabakman, S. M., Welsher, K., Wang, H., Wang, X., Dai, H. 2010; 132 (45): 15920-15923


    The photoluminescence (PL) quantum yield of single-walled carbon nanotubes (SWNTs) is relatively low, with various quenching effects by metallic species reported in the literature. Here, we report the first case of metal enhanced fluorescence (MEF) of surfactant-coated carbon nanotubes on nanostructured gold substrates. The photoluminescence quantum yield of SWNTs is observed to be enhanced more than 10-fold. The dependence of fluorescence enhancement on metal-nanotube distance and on the surface plasmon resonance (SPR) of the gold substrate for various SWNT chiralities is measured to reveal the mechanism of enhancement. Surfactant-coated SWNTs in direct contact with metal exhibit strong MEF without quenching, suggesting a small quenching distance for SWNTs on the order of the van der Waals distance, beyond which the intrinsically fast nonradiative decay rate in nanotubes is little enhanced by metal. The metal enhanced fluorescence of SWNTs is attributed to radiative lifetime shortening through resonance coupling of SWNT emission to the reradiating dipolar plasmonic modes in the metal.

    View details for DOI 10.1021/ja1087997

    View details for PubMedID 20979398

  • Facile Fabrication of Two-Dimensionally Ordered Macroporous Silver Thin Films and Their Application in Molecular Sensing ADVANCED FUNCTIONAL MATERIALS Hong, G., Li, C., Qi, L. 2010; 20 (21): 3774–83
  • Facile Fabrication of Honeycomb-Patterned Thin Films of Amorphous Calcium Carbonate and Mosaic Calcite CHEMISTRY OF MATERIALS Li, C., Hong, G., Yu, H., Qi, L. 2010; 22 (10): 3206–11

    View details for DOI 10.1021/cm100363a

    View details for Web of Science ID 000277635000025

  • Nanosphere Lithography at the Gas/Liquid Interface: A General Approach toward Free-Standing High-Quality Nanonets CHEMISTRY OF MATERIALS Li, C., Hong, G., Qi, L. 2010; 22 (2): 476–81

    View details for DOI 10.1021/cm9031946

    View details for Web of Science ID 000273580700026

  • Seeding-Growth of Helical Mesoporous Silica Nanofibers Templated by Achiral Cationic Surfactant LANGMUIR Zhou, L., Hong, G., Qi, L., Lu, Y. 2009; 25 (11): 6040–44


    Helical mesoporous silica nanofibers with parallel nanochannels were synthesized in high yield via a novel seeding-growth method by using the achiral cationic surfactant cetyltrimethylammonium bromide (CTAB) as template without auxiliary additives. A general entropy-driven model taking into account the icelike structure water due to the hydrophobic effect was proposed to explain the formation of helical mesoporous silica nanofibers. It was indicated that helical silica mesostructures could result from a thick layer of highly ordered icelike water around thin silicate seed rods with a proper concentration, which was verified by the effect of various anions and organic additives on the formation of helical mesoporous silica.

    View details for DOI 10.1021/la901083u

    View details for Web of Science ID 000266604000009

    View details for PubMedID 19425562

  • Wet Chemical Approaches to Patterned Arrays of Well-Aligned ZnO Nanopillars Assisted by Monolayer Colloidal Crystals CHEMISTRY OF MATERIALS Li, C., Hong, G., Wang, P., Yu, D., Qi, L. 2009; 21 (5): 891–97

    View details for DOI 10.1021/cm802839u

    View details for Web of Science ID 000263891700016