Publications by authors named "Bingyang Zhang"

17 Publications

  • Page 1 of 1

Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization.

Pharmaceutics 2021 Apr 9;13(4). Epub 2021 Apr 9.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide SA5005, Australia.

Ferritin, one of the most investigated protein nanocages, is considered as a promising drug carrier because of its advantageous stability and safety. However, its short half-life and undesirable tumor targeting ability has limited its usage in tumor treatment. In this work, two types of functional peptides, half-life extension peptide PAS, and tumor targeting peptide RGDK (Arg-Gly-Asp-Lys), are inserted to human heavy-chain ferritin (HFn) at C-terminal through flexible linkers with two distinct enzyme cleavable sites. Structural characterizations show both HFn and engineered HFns can assemble into nanoparticles but with different apparent hydrodynamic volumes and molecular weights. RGDK peptide enhanced the internalization efficiency of HFn and showed a significant increase of growth inhibition against 4T1 cell line in vitro. Pharmacokinetic study in vivo demonstrates PAS peptides extended ferritin half-life about 4.9 times in Sprague Dawley rats. RGDK peptides greatly enhanced drug accumulation in the tumor site rather than in other organs in biodistribution analysis. Drug loaded PAS-RGDK functionalized HFns curbed tumor growth with significantly greater efficacies in comparison with drug loaded HFn.
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http://dx.doi.org/10.3390/pharmaceutics13040521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070472PMC
April 2021

TWIST2 and the PPAR signaling pathway are important in the progression of nonalcoholic steatohepatitis.

Lipids Health Dis 2021 Apr 20;20(1):39. Epub 2021 Apr 20.

Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, 250014, P. R. China.

Background: To investigate the roles of the transcription factors twist family bHLH transcription factor 1 (TWIST1), twist family bHLH transcription factor 2 (TWIST2), and peroxisome proliferator activated receptor gamma (PPARγ) in the progression of nonalcoholic steatohepatitis.

Methods: The protein levels of TWIST1, TWIST2 and PPARγ were determined in the serum of nonalcoholic fatty liver disease (NAFLD) patients and healthy controls by enzyme-linked immunosorbent assay (ELISA). An in vivo model for fatty liver was established by feeding C57BL/6 J mice a high-fat diet (HFD). An in vitro model of steatosis was established by treating LO-2 cells with oleic acid (OA). RNA sequencing was performed on untreated and OA-treated LO-2 cells followed by TWIST1, TWIST2 and PPARγ gene mRNA levels analysis, Gene Ontology (GO) enrichment and pathway analysis.

Results: The TWIST2 serum protein levels decreased significantly in all fatty liver groups (P < 0.05), while TWIST1 varied. TWIST2 tended to be lower in mice fed an HFD and was significantly lower at 3 months. Similarly, in the in vitro model, the TWIST2 protein level was downregulated significantly at 48 and 72 h after OA treatment. RNA sequencing of LO-2 cells showed an approximately 2.3-fold decrease in TWIST2, with no obvious change in TWIST1 and PPARγ. The PPAR signaling pathway was enriched, with 4 genes upregulated in OA-treated cells (P = 0.0018). The interleukin (IL)-17 and tumor necrosis factor (TNF) signaling pathways were enriched in OA-treated cells.

Conclusions: The results provide evidence that the TWIST2 and PPAR signaling pathways are important in NAFLD and shed light on a potential mechanism of steatosis.
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http://dx.doi.org/10.1186/s12944-021-01458-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059034PMC
April 2021

Sacraoxides A-G, Bioactive Cembranoids from Gum Resin of .

Front Chem 2021 30;9:649287. Epub 2021 Mar 30.

School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Seven undescribed cembranoids, sacraoxides A-G (-) were isolated from the gum resin of . Their structures were elucidated by extensive physicochemical and spectroscopic analysis, as well as ECD calculation, modified Mosher's method and X-ray diffraction crystallography. Compounds and exhibited inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells with IC values of 24.9 ± 1.7 and 36.4 ± 2.9 M.
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http://dx.doi.org/10.3389/fchem.2021.649287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044883PMC
March 2021

Stability of Engineered Ferritin Nanovaccines Investigated by Combined Molecular Simulation and Experiments.

J Phys Chem B 2021 04 7;125(15):3830-3842. Epub 2021 Apr 7.

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, South Australia 5005, Australia.

Human ferritin is regarded as an attractive and promising vaccine platform because of its uniform structure, good plasticity, and desirable thermal and chemical stabilities. Besides, it is biocompatible and presumed safe when used as a vaccine carrier. However, there is a lack of knowledge of how different antigen insertion sites on the ferritin nanocage impact the resulting protein stability and performance. To address this question, we selected Epstein-Barr nuclear antigen 1 as a model epitope and fused it at the DNA level with different insertion sites, namely, the N- and C-termini of ferritin, to engineer proteins E1F1 and F1E1, respectively. Protein properties including hydrophobicity and thermal, pH, and chemical stability were investigated both by molecular dynamics (MD) simulation and by experiments. Both methods demonstrate that the insertion site plays an important role in protein properties. The C-terminus insertion (F1E1) leads to a less hydrophobic surface and more tolerance to the external influence of high temperature, pH, and high concentration of chemical denaturants compared to N-terminus insertion (E1F1). Simulated protein hydrophobicity and thermal stability by MD were in high accordance with experimental results. Thus, MD simulation can be used as a valuable tool to engineer nanovaccine candidates, cutting down costs by reducing the experimental effort and accelerating vaccine design.
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http://dx.doi.org/10.1021/acs.jpcb.1c00276DOI Listing
April 2021

Paraquat-activated BV-2 microglia induces neuroinflammatory responses in the neuron model through NF-κB signaling pathway.

Toxicol In Vitro 2021 Apr 4;72:105076. Epub 2021 Jan 4.

Department of Occupational and Environmental Health, School of Public Health and Management, Ningxia Medical University, Yin Chuan, China. Electronic address:

Paraquat (PQ), a non-selective contact herbicide, has been generally accepted as one of the environmental neurotoxicants. Despite the direct evidence that PQ could induce inflammation responses in microglia, little is known about the effects of the inflammatory microglia on neurons. Thus in the present study, mouse primary cortical neurons and PC12 cells, widely-used in vitro neuron models for neurotoxicity research were applied to investigate the neuroinflammatory effects of PQ-activated microglia on neurons. We observed that the secretion levels of TNF-α and IL-6 in PC12 cells were markedly increased upon treatment with the supernatants of inflammatory BV2 microglia, and NF-κB p65 protein expression was also elevated. Specific inhibition of NF-κB by PDTC dramatically attenuated the increase of TNF-α and IL-6 release. These results suggested that PQ-induced inflammatory microglia exerts secondary inflammatory effects on neurons through activation of NF-κB pathway.
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http://dx.doi.org/10.1016/j.tiv.2021.105076DOI Listing
April 2021

In vitro preparation of uniform and nucleic acid free hepatitis B core particles through an optimized disassembly-purification-reassembly process.

Protein Expr Purif 2021 02 6;178:105747. Epub 2020 Sep 6.

National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, PR China. Electronic address:

Structure heterogeneity and host nucleic acids contamination are two major problems for virus-like particles (VLPs) produced by various host cells. In this study, an in vitro optimized disassembly-purification-reassembly process was developed to obtain uniform and nucleic acid free hepatitis B core (HBc) based VLPs from E. coli fermentation. The process started with ammonium sulfate precipitation of all heterogeneous HBc structures after cell disintegration. Then, dissolution and disassembly of pellets into basic subunits were carried out under the optimized disassembly condition. All contaminants, including host nucleic acids and proteins, were efficiently removed with affinity chromatography. The purified subunits reassembled into VLPs by final removal of the chaotropic agent. Two uniform and nucleic acid free HBc-based VLPs, truncated HBc and chimeric HBc-MAGE3 I, were successfully prepared. It was found that disassembly degree of HBc-based VLPs had a great influence on the protein yield, nucleic acid removal and reassembly efficiency. 4 M urea was optimal because lower concentration would not disassemble the particles completely while higher concentration would further denature the subunits into disordered aggregate and could not be purified and reassembled efficiently. For removal of strong binding nucleic acids such as in the case of HBc-MAGE3 I, benzonase nuclease was added to the disassembly buffer before affinity purification. Through the optimized downstream process, uniform and nucleic acid free HBc VLPs and HBc-MAGE3 I VLPs were obtained with purities above 90% and yields of 55.2 and 43.0 mg/L, respectively. This study would be a reference for efficient preparation of other VLPs.
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http://dx.doi.org/10.1016/j.pep.2020.105747DOI Listing
February 2021

A Population-Based Analysis of Mucoepidermoid Carcinoma of the Oral Cavity.

Laryngoscope 2021 03 21;131(3):E857-E863. Epub 2020 Jul 21.

Department of Hemangioma and Vascular Malformation Surgery, People's Hospital of Henan University, Henan Provincial People's Hospital, Zhengzhou, China.

Objectives: To identify survival outcomes for patients with mucoepidermoid carcinoma (MEC) of the oral cavity and the effects of different prognostic factors on survival.

Study Design: Retrospective cohort study using a national database.

Methods: Retrospective, population-based cohort study of patients in the Surveillance, Epidemiology and End Results (SEER) database who were diagnosed with MEC of the oral cavity from 1973 to 2016. Overall survival (OS) and disease-specific survival (DSS) were calculated.

Results: A total of 1693 patients with MEC of the oral cavity were included. Of those, there are 696 males and 997 females, the average age at diagnosis being 52.4 years. The vast majority of cases (86.4%) presented with stage I and stage II disease. A total of 206 patients had received both surgical and radiation therapy (RT), while 1338 patients just had undergone only surgery and 149 with no treatment. On multivariate analysis, advanced age, stage, and histologic grade were associated with worse OS and DSS. Surgical therapy was an independent favorable predictor of OS and DSS. For radiotherapy, multivariate analysis showed that it was associated with worse DSS, whereas there was no significant difference in OS.

Conclusion: MEC of the oral cavity is associated with a generally favorable prognosis. Advanced age, stage, and histologic grade were independent negative prognostic factors for survival, and surgery was the main treatment to improve survival.

Level Of Evidence: 4 Laryngoscope, 131:E857-E863, 2021.
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http://dx.doi.org/10.1002/lary.28905DOI Listing
March 2021

3D bioprinting of cell-laden electroconductive MXene nanocomposite bioinks.

Nanoscale 2020 Aug;12(30):16069-16080

School of Chemical Engineering and Advanced Materials, The University of Adelaide, Adelaide, SA 5005, Australia.

MXenes, a new family of burgeoning two-dimensional (2D) transition metal carbides/nitrides, have been extensively explored in recent years owing to their outstanding properties such as a large specific surface area, high electrical conductivity, low toxicity, and biodegradability. Numerous efforts have been devoted to exploring MXenes for various biomedical applications such as cancer therapy, bioimaging, biosensing, and drug delivery. However, the potential application of MXene nanosheets in tissue engineering has been almost overlooked despite their excellent performance in other biomedical applications. The overarching goal of this paper is to demonstrate the potential of MXene cell-laden bioinks for tissue engineering and their ability to assemble functional scaffolds to regenerate damaged tissue via 3D bioprinting. We formulate a new electroconductive cell-laden bioink composed of Ti3C2 MXene nanosheets dispersed homogeneously within hyaluronic acid/alginate (HA/Alg) hydrogels and showed its performance for extrusion-based 3D bioprinting. The prepared hydrogel bioinks with MXenes display excellent rheological properties, which allows the fabrication of multilayered 3D structures with high resolution and shape retention. Moreover, the introduction of Ti3C2 MXene nanosheets within the HA/Alg hydrogel introduces electrical conductivity to the ink, addressing the poor electrical conductivity of the current bioinks that mismatch with the physico-chemical properties of tissue. In addition, the MXene nanocomposite ink with encapsulated Human Embryonic Kidney 293 (HEK-293) cells displayed high cell viability (>95%) in both bulk hydrogel and 3D bioprinted structures. These results suggest that MXene nanocomposite bioinks and their 3D bioprinting with high electrical conductivity, biocompatibility and degradability can synergize some new applications for tissue and neural engineering.
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http://dx.doi.org/10.1039/d0nr02581jDOI Listing
August 2020

3D printing of cell-laden electroconductive bioinks for tissue engineering applications.

J Mater Chem B 2020 07;8(27):5862-5876

School of Chemical Engineering & Advanced Materials, The University of Adelaide, Adelaide, SA 5005, Australia.

Bioprinting is an emerging powerful fabrication method, which enables the rapid assembly of 3D bioconstructs with dispensing cell-laden bioinks in pre-designed locations. However, to translate this technology into real applications, there are still a number of challenges that need to be addressed. First, the current inks are generally composed of polymeric materials with poor electrical conductivity that mismatches with the native tissue environment. The second challenge associated with the 3D bioprinting of hydrogel-based bioinks is the fabrication of anatomical-size constructs without any loss of shape fidelity and resolution. To address these challenges, in this work, we introduced a biocompatible bioink associated with current 3D bioprinting by combining methylcellulose and kappa-carrageenan (MC/κCA) hydrogels with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) conducting polymers. The prepared ink exhibited highly thixotropic behaviour, which could be tuned via changing the concentration of MC and κCA to obtain easy printing with high shape fidelity. The ink was able to fabricate physiological-scale constructs without requiring a secondary support bath. In addition, varying the concentration of PEDOT:PSS could control the electrical conductivity of the ink. Moreover, the encapsulated human embryonic kidney 293 (HEK-293) cells in bulk hydrogels and 3D bioprinted structures maintained high cell viability (>96%) over a week, confirming the in vitro biocompatibility of the ink. Overall, these findings indicate that the MC/κCA/PEDOT:PSS bioink can be promising in biomedical applications, which improved the electroconductivity of bioinks and can exploit the advantage of conductive polymers in the 3D bioprinting technology.
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http://dx.doi.org/10.1039/d0tb00627kDOI Listing
July 2020

Comprehensive characterization and identification of antioxidants in Folium Artemisiae Argyi using high-resolution tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2017 Sep 19;1063:84-92. Epub 2017 Aug 19.

Yunnan Food Safety Research Institute, Kunming University of Science and Technology, Kunming 650500, PR China. Electronic address:

Antioxidants from natural sources, such as vegetables and fruits, are attracting more and more interest. In this work, we evaluated the antioxidant potential of Folium Artemisia Argyi, a traditional Chinese herb medicine and food supplement. The total phenolic content, total flavonoid content, and antioxidant ability of the crude extracts and fractions obtained from consecutively partition of n-hexane, ethyl acetate, and n-butanol were measured and compared. Ethyl acetate fraction shows the highest total phenolic and flavonoid contents and highest antioxidant capability with regard to DPPH, ABTS, superoxide anion free radical scavenging ability, and ferric-reducing antioxidant power. In addition, the potential antioxidant components were screened by DPPH-UHPLC-MS experiments and subsequently characterized by using high-resolution tandem mass spectrometry. This work finally identified 45 antioxidants, including organic acids, phenolic compounds, flavonoids, and methoxylated flavonoids. The results suggested that Folium Artemisiae Argyi is a potential inexpensive resource of natural antioxidants.
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http://dx.doi.org/10.1016/j.jchromb.2017.08.021DOI Listing
September 2017

GC-MS Fingerprinting Combined with Chemometric Methods Reveals Key Bioactive Components in Acori Tatarinowii Rhizoma.

Int J Mol Sci 2017 Jul 3;18(7). Epub 2017 Jul 3.

Yunnan Food Safety Research Institute, Kunming University of Science and Technology, Kunming 650500, China.

This present study aims to identify the key bioactive components in (ATR), a traditional Chinese medicine (TCM) with various bioactivities. Partial least squares regression (PLSR) was employed to describe the relationship between the radical scavenging activity and the volatile components. The PLSR model was improved by outlier elimination and variable selection and was evaluated by 10-fold cross-validation and external validation in this study. Based on the PLSR model, eleven chemical components were identified as the key bioactive components by variable importance in projection. The final PLS regression model with these components has good predictive ability. The ² was 0.8284, and the root mean square error for prediction was 2.9641. The results indicated that the eleven components could be a pattern to predict the radical scavenging activity of ATR. In addition, we did not find any specific relationship between the radical scavenging ability and the habitat of the ATRs. This study proposed an efficient strategy to predict bioactive components using the combination of quantitative chromatography fingerprints and PLS regression, and has potential perspective for screening bioactive components in complex analytical systems, such as TCM.
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http://dx.doi.org/10.3390/ijms18071342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535835PMC
July 2017

Cell-penetrating peptide-labelled smart polymers for enhanced gene delivery.

Eng Life Sci 2017 Feb 4;17(2):193-203. Epub 2016 Oct 4.

School of Chemical Engineering University of Adelaide Adelaide Australia.

Highly efficient gene delivery vehicles are pursued to progress gene therapy. In this study, we developed the cell-penetrating peptide-labelled and degradable gene carriers for efficient external gene transfection. The cationic carriers were prepared by coupling low-molecular-weight polyethylenimine (PEI800) with 4'4-dithiodibutyric acid (DA), and HIV-1 Trans-Activator of Transcription (TAT) was conjugated to the carriers as a penetrating peptide. The resulted PEI-DA-TAT was able to condense plasmid DNA (pDNA) into a complex with a hydrodynamic size of around 150 nm under a neutral condition. PEI-DA-TAT showed negligible cytotoxicity to both Hela and HEK 293 cells with the cell viability of more than 80% beyond the carrier concentration of 50 μg/mL. This new carrier displayed better performance in regard to DNA transfection efficiency in comparison with the carriers of non-TAT labelled PEI-DA, commercial PEI25K and low-molecular-weight PEI (PEI800). The transfection efficiency of PEI-DA-TAT was increased by 8% compared with PEI-DA and PEI25K. The experimental findings suggested that the developed PEI-DA-TAT is a promising carrier for efficient DNA delivery with low cytotoxicity for gene therapy.
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http://dx.doi.org/10.1002/elsc.201600069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999197PMC
February 2017

Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia.

Am J Hematol 2012 Jan 4;87(1):45-50. Epub 2011 Nov 4.

Department of Medicine, Division of Hematology, Stanford University School of Medicine, California, USA.

Temozolomide sensitivity is determined by methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter. This study assessed whether the temozolomide dose can be tailored by MGMT promoter status and whether protracted, low-dose temozolomide can "prime" blasts in patients with unmethylated MGMT (unMGMT). Elderly patients with high-risk AML were stratified by MGMT methylation. Patients with methylated MGMT (mMGMT) received temozolomide 200 mg/m(2) orally for 7 days every 4 weeks, while patients with unMGMT received temozolomide 100 mg/m(2) orally for 14 days followed by 200 mg/m(2) orally for 7 days every 6weeks. Of 36 patients (median age, 75 years), 31 (86%) had an unMGMT promoter. Overall response rate for the entire cohort was 36%. Patients with mMGMT and unMGMT had similar response rates (40% vs. 29%). Median duration of response and overall survival (OS) among responders were 29 and 35 weeks, respectively. Induction deaths (ID) occurred in 25% of patients, mostly caused by disease progression. Hematological toxicities were the most common adverse event. Toxicities were similar between patients on conventional versus protracted schedules. High HCT-CI scores were predictive of lower CR rate, higher ID, and shorter OS, while bone marrow blast count <50% at screening predicted for improved responses. Temozolomide, dosed according to MGMT methylation status, demonstrated modest clinical activity in elderly patients with AML, especially in those presenting with fewer comorbidities and low disease burden. The trial was registered on www.ClinicalTrials.gov as #NCT00611247.
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http://dx.doi.org/10.1002/ajh.22191DOI Listing
January 2012

Complete quantum control of a single quantum dot spin using ultrafast optical pulses.

Nature 2008 Nov;456(7219):218-21

E. L. Ginzton Laboratory, Stanford University, Stanford, California 94305, USA.

A basic requirement for quantum information processing systems is the ability to completely control the state of a single qubit. For qubits based on electron spin, a universal single-qubit gate is realized by a rotation of the spin by any angle about an arbitrary axis. Driven, coherent Rabi oscillations between two spin states can be used to demonstrate control of the rotation angle. Ramsey interference, produced by two coherent spin rotations separated by a variable time delay, demonstrates control over the axis of rotation. Full quantum control of an electron spin in a quantum dot has previously been demonstrated using resonant radio-frequency pulses that require many spin precession periods. However, optical manipulation of the spin allows quantum control on a picosecond or femtosecond timescale, permitting an arbitrary rotation to be completed within one spin precession period. Recent work in optical single-spin control has demonstrated the initialization of a spin state in a quantum dot, as well as the ultrafast manipulation of coherence in a largely unpolarized single-spin state. Here we demonstrate complete coherent control over an initialized electron spin state in a quantum dot using picosecond optical pulses. First we vary the intensity of a single optical pulse to observe over six Rabi oscillations between the two spin states; then we apply two sequential pulses to observe high-contrast Ramsey interference. Such a two-pulse sequence realizes an arbitrary single-qubit gate completed on a picosecond timescale. Along with the spin initialization and final projective measurement of the spin state, these results demonstrate a complete set of all-optical single-qubit operations.
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http://dx.doi.org/10.1038/nature07530DOI Listing
November 2008

Generation and transfer of single photons on a photonic crystal chip.

Opt Express 2007 Apr;15(9):5550-8

We present a basic building block of a quantum network consisting of a quantum dot coupled to a source cavity, which in turn is coupled to a target cavity via a waveguide. The single photon emission from the high-Q/V source cavity is characterized by twelve-fold spontaneous emission (SE) rate enhancement, SE coupling efficiency beta ~ 0.98 into the source cavity mode, and mean wavepacket indistinguishability of ~67%. Single photons are efficiently transferred into the target cavity via the waveguide, with a target/source field intensity ratio of 0.12 +/- 0.01. This system shows great promise as a building block of future on-chip quantum information processing systems.
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http://dx.doi.org/10.1364/oe.15.005550DOI Listing
April 2007

Controlling the spontaneous emission rate of single quantum dots in a two-dimensional photonic crystal.

Phys Rev Lett 2005 Jul 1;95(1):013904. Epub 2005 Jul 1.

Ginzton Laboratory, Stanford University, Stanford, California 94305, USA.

We observe large spontaneous emission rate modification of individual InAs quantum dots (QDs) in a 2D photonic crystal with a modified, high-Q single-defect cavity. Compared to QDs in a bulk semiconductor, QDs that are resonant with the cavity show an emission rate increase of up to a factor of 8. In contrast, off-resonant QDs indicate up to fivefold rate quenching as the local density of optical states is diminished in the photonic crystal. In both cases, we demonstrate photon antibunching, showing that the structure represents an on-demand single photon source with a pulse duration from 210 ps to 8 ns. We explain the suppression of QD emission rate using finite difference time domain simulations and find good agreement with experiment.
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http://dx.doi.org/10.1103/PhysRevLett.95.013904DOI Listing
July 2005

Efficient source of single photons: a single quantum dot in a micropost microcavity.

Phys Rev Lett 2002 Dec 13;89(23):233602. Epub 2002 Nov 13.

Quantum Entanglement Project, ICORP, JST, E. L. Ginzton Laboratory, Stanford University, Stanford, California 94305, USA.

We have demonstrated efficient production of triggered single photons by coupling a single semiconductor quantum dot to a three-dimensionally confined optical mode in a micropost microcavity. The efficiency of emitting single photons into a single-mode traveling wave is approximately 38%, which is nearly 2 orders of magnitude higher than for a quantum dot in bulk semiconductor material. At the same time, the probability of having more than one photon in a given pulse is reduced by a factor of 7 as compared to light with Poissonian photon statistics.
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http://dx.doi.org/10.1103/PhysRevLett.89.233602DOI Listing
December 2002