Sub-picomolar lateral flow antigen detection with two-wavelength imaging of composite nanoparticles
}, volume={207}, ISSN={["1873-4235"]}, DOI={10.1016/j.bios.2022.114133}, abstractNote={Lateral flow tests, commonly based on metal plasmonic nanoparticles, are rapid, robust, and low-cost. However, improvements in analytical sensitivity are required to allow detection of low-abundance biomarkers, for example detection of low antigen concentrations for earlier or asymptomatic diagnosis of infectious diseases. Efforts to improve sensitivity often require changes to the assay. Here, we developed optical methods to improve the sensitivity of absorption-based lateral flow tests, requiring no assay modifications to existing tests. We experimentally compared five different lock-in and subtraction-based methods, exploiting the narrow plasmonic peak of gold nanoparticles for background removal by imaging at different light wavelengths. A statistical framework and three fitting models were used to compare limits of detection, giving a 2.0-5.4-fold improvement. We then demonstrated the broad applicability of the method to an ultrasensitive assay, designing 530 nm composite nanoparticles to increase the particle volume, and therefore light absorption per particle, whilst retaining the plasmonic peak to allow background removal and without adding any assay steps. This multifaceted, modular approach gave a combined 58-fold improvement in the fundamental limit of detection using a biotin-avidin model over 50 nm gold nanoparticles with single-wavelength imaging. Applying to a sandwich assay for the detection of HIV capsid protein gave a limit of detection of 170 fM. Additionally, we developed an open-source software tool for performing the detection limit analysis used in this work.}, journal={BIOSENSORS & BIOELECTRONICS}, author={Miller, Benjamin S. and Thomas, Michael R. and Banner, Matthew and Kim, Jeongyun and Chen, Yiyun and Wei, Qingshan and Tseng, Derek K. and Goeroecs, Zoltan S. and Ozcan, Aydogan M. and Stevens, Molly M. A. and et al.}, year={2022}, month={Jul} } @article{mohammad_katkam_wei_2022, title={A Sensitive and Nonoptical CRISPR Detection Mechanism by Sizing Double-Stranded lambda DNA Reporter}, volume={11}, ISSN={["1521-3773"]}, url={https://doi.org/10.1002/anie.202213920}, DOI={10.1002/anie.202213920}, abstractNote={Abstract}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Mohammad, Noor and Katkam, Shrinivas S. and Wei, Qingshan}, year={2022}, month={Nov} } @article{mohammad_katkam_wei_2022, title={A Sensitive and Nonoptical CRISPR Detection Mechanism by Sizing Double‐Stranded λ DNA Reporter}, url={https://doi.org/10.1002/ange.202213920}, DOI={10.1002/ange.202213920}, abstractNote={Abstract}, journal={Angewandte Chemie}, author={Mohammad, Noor and Katkam, Shrinivas S. and Wei, Qingshan}, year={2022}, month={Dec} } @article{wang_pirzada_xie_barbieri_hossain_opperman_pal_wei_parsons_khan_2022, title={Creating hierarchically porous banana paper-metal organic framework (MOF) composites with multifunctionality}, volume={28}, ISSN={["2352-9407"]}, url={https://doi.org/10.1016/j.apmt.2022.101517}, DOI={10.1016/j.apmt.2022.101517}, abstractNote={We report a robust approach to integrate metal-organic frameworks (MOF) via vapor phase synthesis on a cost-effective and mechanically durable fibrous banana paper (BP) substrate developed from lignocellulosic biomass. The unique hollow fibrous structure of BP combined with the methodology used produces MOF-fiber composites with uniform MOF distribution and enhanced functionalities, with minimal use of organic solvents. The BP-MOF composites demonstrate a high surface area of 552 m2/g and uniform surface growth of MOF on them. Mechanical strength and bending flexibility of the substrate is well retained after the MOF growth, while the hollow tubular nature and hierarchical porosity of the BP facilitate gas diffusion. The BP-MOF composites demonstrate strong antibacterial activity with 99.2% of E.coli destroyed within the first hour of incubation. Preliminary studies with smartphone-based volatile organic compound (VOC) sensor show enhanced 1-octen-3-ol vapor absorption on BP-MOF, indicating its potential for VOC capture and sensing. We believe that the sustainable nature and flexibility of the lignocellulosic BP substrate taken together with uniform growth of MOF on the hierarchically porous BP impart impressive attributes to these composites, which can be explored in diverse applications.}, journal={APPLIED MATERIALS TODAY}, publisher={Elsevier BV}, author={Wang, Siyao and Pirzada, Tahira and Xie, Wenyi and Barbieri, Eduardo and Hossain, Oindrila and Opperman, Charles H. and Pal, Lokendra and Wei, Qingshan and Parsons, Gregory N. and Khan, Saad A.}, year={2022}, month={Aug} } @article{hetzler_wang_krafft_jamalzadegan_overton_kudenov_ligler_wei_2022, title={Flexible sensor patch for continuous carbon dioxide monitoring}, volume={10}, ISSN={["2296-2646"]}, DOI={10.3389/fchem.2022.983523}, abstractNote={Monitoring and measurement of carbon dioxide (CO2) is critical for many fields. The gold standard CO2 sensor, the Severinghaus electrode, has remained unchanged for decades. In recent years, many other CO2 sensor formats, such as detection based upon pH-sensitive dyes, have been demonstrated, opening the door for relatively simple optical detection schemes. However, a majority of these optochemical sensors require complex sensor preparation steps and are difficult to control and repeatably execute. Here, we report a facile CO2 sensor generation method that suffers from none of the typical fabrication issues. The method described here utilizes polydimethylsiloxane (PDMS) as the flexible sensor matrix and 1-hydroxypyrene-3,6,8-trisulfonate (HPTS), a pH-sensitive dye, as the sensing material. HPTS, a base (NaOH), and glycerol are loaded as dense droplets into a thin PDMS layer which is subsequently cured around the droplet. The fabrication process does not require prior knowledge in chemistry or device fabrication and can be completed as quickly as PDMS cures (∼2 h). We demonstrate the application of this thin-patch sensor for in-line CO2 quantification in cell culture media. To this end, we optimized the sensing composition and quantified CO2 in the range of 0–20 kPa. A standard curve was generated with high fidelity (R2 = 0.998) along with an analytical resolution of 0.5 kPa (3.7 mm Hg). Additionally, the sensor is fully autoclavable for applications requiring sterility and has a long working lifetime. This flexible, simple-to-manufacture sensor has a myriad of potential applications and represents a new, straightforward means for optical carbon dioxide measurement.}, journal={FRONTIERS IN CHEMISTRY}, author={Hetzler, Zach and Wang, Yan and Krafft, Danny and Jamalzadegan, Sina and Overton, Laurie and Kudenov, Michael W. and Ligler, Frances S. and Wei, Qingshan}, year={2022}, month={Sep} } @article{son_lee_wang_samson_wei_zhu_you_2022, title={Integrating charge mobility, stability and stretchability within conjugated polymer films for stretchable multifunctional sensors}, volume={13}, ISSN={["2041-1723"]}, url={https://doi.org/10.1038/s41467-022-30361-0}, DOI={10.1038/s41467-022-30361-0}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, author={Son, Sung Yun and Lee, Giwon and Wang, Hongyu and Samson, Stephanie and Wei, Qingshan and Zhu, Yong and You, Wei}, year={2022}, month={May} } @article{mohammad_katkam_wei_2022, title={Recent Advances in Clustered Regularly Interspaced Short Palindromic Repeats-Based Biosensors for Point-of-Care Pathogen Detection}, volume={7}, ISSN={["2573-1602"]}, url={https://doi.org/10.1089/crispr.2021.0146}, DOI={10.1089/crispr.2021.0146}, abstractNote={Infectious pathogens are pressing concerns due to their heavy toll on global health and socioeconomic infrastructure. Rapid, sensitive, and specific pathogen detection methods are needed more than ever to control disease spreading. The fast evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics (CRISPR-Dx) has opened a new horizon in the field of molecular diagnostics. This review highlights recent efforts in configuring CRISPR technology as an efficient diagnostic tool for pathogen detection. It starts with a brief introduction of different CRISPR-Cas effectors and their working principles for disease diagnosis. It then focuses on the evolution of laboratory-based CRISPR technology toward a potential point-of-care test, including the development of new signaling mechanisms, elimination of preamplification and sample pretreatment steps, and miniaturization of CRISPR reactions on digital assay chips and lateral flow devices. In addition, promising examples of CRISPR-Dx for pathogen detection in various real samples, such as blood, saliva, nasal swab, plant, and food samples, are highlighted. Finally, the challenges and perspectives of future development of CRISPR-Dx for infectious disease monitoring are discussed.}, journal={CRISPR JOURNAL}, author={Mohammad, Noor and Katkam, Shrinivas Siddhivinayak and Wei, Qingshan}, year={2022}, month={Jul} } @article{skolrood_wang_zhang_wei_2022, title={Single-molecule and particle detection on true portable microscopy platforms}, volume={4}, ISSN={["2666-0539"]}, DOI={10.1016/j.snr.2021.100063}, abstractNote={Point-of-care technologies (POCT) that enable early disease detection and therapeutic monitoring are crucial for the next generation of diagnostics and personalized medicine. Meanwhile, there is a global need for low-cost POCT that makes advanced diagnostic tools accessible to resource-limited settings. Recently, several mobile imaging platforms for single-molecule and particle detection have been developed, which greatly improve the detection sensitivity of molecular assays. This review highlights emerging technologies that achieve single-molecule and particle optical detection on true portable platforms. Miniature, high-sensitivity imaging devices based on smartphones, single-board computers (i.e., Raspberry Pi systems), lab-on-a-chip systems, and 3D-printed microscopy platforms are discussed.}, journal={SENSORS AND ACTUATORS REPORTS}, author={Skolrood, Lydia and Wang, Yan and Zhang, Shengwei and Wei, Qingshan}, year={2022}, month={Nov} } @article{lee_zarei_wei_zhu_lee_2022, title={Surface Wrinkling for Flexible and Stretchable Sensors}, volume={9}, ISSN={["1613-6829"]}, url={https://doi.org/10.1002/smll.202203491}, DOI={10.1002/smll.202203491}, abstractNote={Abstract}, journal={SMALL}, author={Lee, Giwon and Zarei, Mohammad and Wei, Qingshan and Zhu, Yong and Lee, Seung Goo}, year={2022}, month={Sep} } @article{ning_yu_zhang_huang_tian_lin_niu_golden_hensley_threeton_et al._2021, title={A smartphone-read ultrasensitive and quantitative saliva test for COVID-19}, volume={7}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.abe3703}, abstractNote={An isolation-free smartphone-based saliva assay can diagnose COVID-19 cases and quantify viral load within 15 min.}, number={2}, journal={SCIENCE ADVANCES}, author={Ning, Bo and Yu, Tao and Zhang, Shengwei and Huang, Zhen and Tian, Di and Lin, Zhen and Niu, Alex and Golden, Nadia and Hensley, Krystle and Threeton, Breanna and et al.}, year={2021}, month={Jan} } @article{trofymchuk_glembockyte_grabenhorst_steiner_vietz_close_pfeiffer_richter_schuette_selbach_et al._2021, title={Addressable nanoantennas with cleared hotspots for single-molecule detection on a portable smartphone microscope}, volume={12}, ISSN={["2041-1723"]}, DOI={10.1038/s41467-021-21238-9}, abstractNote={Abstract}, number={1}, journal={NATURE COMMUNICATIONS}, author={Trofymchuk, Kateryna and Glembockyte, Viktorija and Grabenhorst, Lennart and Steiner, Florian and Vietz, Carolin and Close, Cindy and Pfeiffer, Martina and Richter, Lars and Schuette, Max L. and Selbach, Florian and et al.}, year={2021}, month={Feb} } @article{joh_heggestad_zhang_anderson_bhattacharyya_wardell_wall_cheng_albarghouthi_liu_et al._2021, title={Cellphone enabled point-of-care assessment of breast tumor cytology and molecular HER2 expression from fine-needle aspirates}, volume={7}, ISSN={["2374-4677"]}, DOI={10.1038/s41523-021-00290-0}, abstractNote={Abstract}, number={1}, journal={NPJ BREAST CANCER}, author={Joh, Daniel Y. and Heggestad, Jacob T. and Zhang, Shengwei and Anderson, Grace R. and Bhattacharyya, Jayanta and Wardell, Suzanne E. and Wall, Simone A. and Cheng, Amy B. and Albarghouthi, Faris and Liu, Jason and et al.}, year={2021}, month={Jul} } @article{yu_zhang_matei_marx_beisel_wei_2021, title={Coupling smartphone and CRISPR-Cas12a for digital and multiplexed nucleic acid detection}, volume={7}, ISSN={["1547-5905"]}, url={https://doi.org/10.1002/aic.17365}, DOI={10.1002/aic.17365}, abstractNote={Abstract}, number={12}, journal={AICHE JOURNAL}, publisher={Wiley}, author={Yu, Tao and Zhang, Shengwei and Matei, Razvan and Marx, William and Beisel, Chase L. and Wei, Qingshan}, year={2021}, month={Jul} } @article{li_wei_han_2021, title={Editorial: Array-Based Sensing Techniques for Clinical, Agricultural Biotechnology, and Environmental Analysis}, volume={9}, ISSN={["2296-2646"]}, DOI={10.3389/fchem.2021.654707}, abstractNote={The array-based sensors, as a class of easy-to-use analytical tools that tracks the pattern-based responses, has emerged as a versatile method for the identification and quantification of chemically diverse analytes, and demonstrated their usefulness in addressing a wide range of analytical challenges (Albert et al., 2000; Han et al., 2017; Li et al., 2019). By using chemically diverse chemoresponsive dyes or biological receptors in combination with chemometric analysis, sensor arrays can be constructed to discriminate various structurally similar analytes or their mixtures. While many biological systems employ a highly specific lock-and-key strategy for molecular recognition, the array-based approach provides an alternative means of creating specificity through pattern recognition of the response from an assembly of cross-reactive sensors, which can be applied to both gaseous and aqueous analytes (Sun et al., 2020). The primary feature of an advanced sensor array, as an analog to the mammalian nose, is that it gives a composite response to target mixtures and provides accurate discrimination between highly similar complex mixtures without the need to know individual components (Potyrailo et al., 2015). To present state-of-the-art research in this field, we launched a Research Topic in Frontiers in Chemistry entitled “Array-Based Sensing Techniques for Clinical, Agricultural Biotechnology, and Environmental Analysis”. This Research Topic included 5 articles, including 1 original research article and 4 reviews, which covered the use of colorimetric, fluorometric, and electrochemical sensor arrays for bioengineering monitoring, bioanalysis, and many other clinical applications. The original research article from Mohs et al. reported a ratiometric sensor array that enabled the prediction and quantification of complex bacterial mixtures; themethod was able to quantify individual components with the accuracy of ∼80% and without the need for acquisition of new reference data or expansion of the training datasets. This approach significantly enlarged the functionality of optical sensor arrays and provided essential insights into data processing for the analysis of biologically complex samples. The other 4 review articles summarized nearly all aspects of the sensor array applications in fundamental research or industrial production. Chen et al. introduced the recent progress of employing aggregation-induced emission luminogens (AIEgens) as fluorescent sensors and in building up sensor arrays for the identification of biological analytes, including biomolecules and bacteria. Examples were incorporated to illustrate the probe design and working mechanism, capability of the sensor array, as well as the clinical implications of these Edited and reviewed by: Alberto Salomone, University of Turin, Italy}, journal={FRONTIERS IN CHEMISTRY}, author={Li, Zheng and Wei, Qingshan and Han, Jinsong}, year={2021}, month={Mar} } @article{lee_wei_zhu_2021, title={Emerging Wearable Sensors for Plant Health Monitoring}, volume={10}, ISSN={["1616-3028"]}, DOI={10.1002/adfm.202106475}, abstractNote={Abstract}, journal={ADVANCED FUNCTIONAL MATERIALS}, author={Lee, Giwon and Wei, Qingshan and Zhu, Yong}, year={2021}, month={Oct} } @article{paul_ostermann_chen_saville_yang_gu_whitfield_ristaino_wei_2021, title={Integrated microneedle-smartphone nucleic acid amplification platform for in-field diagnosis of plant diseases}, volume={187}, ISSN={["1873-4235"]}, url={https://doi.org/10.1016/j.bios.2021.113312}, DOI={10.1016/j.bios.2021.113312}, abstractNote={We demonstrate an integrated microneedle (MN)-smartphone nucleic acid amplification platform for “sample-to-answer” diagnosis of multiplexed plant pathogens within 30 min. This portable system consists of a polymeric MN patch for rapid nucleic acid extraction within a minute and a 3D-printed smartphone imaging device for loop-mediated isothermal amplification (LAMP) reaction and detection. We expanded the extraction of the MN technology for DNA targets as in the previous study (ACS Nano, 2019, 13, 6540–6549) to more fragile RNA biomarkers, evaluated the storability of the extracted nucleic acid samples on MN surfaces, and developed a smartphone-based LAMP amplification and fluorescent reader device that can quantify four LAMP reactions on the same chip. In addition, we have found that the MN patch containing as few as a single needle tip successfully extracted enough RNA for RT-PCR or RT-LAMP analysis. Moreover, MN-extracted RNA samples remained stable on MN surfaces for up to three days. The MN-smartphone platform has been used to detect both Phytophthora infestans DNA and tomato spotted wilt virus (TSWV) RNA down to 1 pg, comparable to the results from a benchtop thermal cycler. Finally, multiplexed detection of P. infestans and TSWV through a single extraction from infected tomato leaves and amplification on the smartphone without benchtop equipment was demonstrated.}, journal={BIOSENSORS & BIOELECTRONICS}, publisher={Elsevier BV}, author={Paul, Rajesh and Ostermann, Emily and Chen, Yuting and Saville, Amanda C. and Yang, Yuming and Gu, Zhen and Whitfield, Anna E. and Ristaino, Jean B. and Wei, Qingshan}, year={2021}, month={Sep} } @misc{silva_tomlinson_onkokesung_sommer_mrisho_legg_adams_gutierrez-vazquez_howard_laverick_et al._2021, title={Plant pest surveillance: from satellites to molecules}, volume={5}, ISSN={["2397-8562"]}, DOI={10.1042/ETLS20200300}, abstractNote={Plant pests and diseases impact both food security and natural ecosystems, and the impact has been accelerated in recent years due to several confounding factors. The globalisation of trade has moved pests out of natural ranges, creating damaging epidemics in new regions. Climate change has extended the range of pests and the pathogens they vector. Resistance to agrochemicals has made pathogens, pests, and weeds more difficult to control. Early detection is critical to achieve effective control, both from a biosecurity as well as an endemic pest perspective. Molecular diagnostics has revolutionised our ability to identify pests and diseases over the past two decades, but more recent technological innovations are enabling us to achieve better pest surveillance. In this review, we will explore the different technologies that are enabling this advancing capability and discuss the drivers that will shape its future deployment.}, number={2}, journal={EMERGING TOPICS IN LIFE SCIENCES}, author={Silva, Goncalo and Tomlinson, Jenny and Onkokesung, Nawaporn and Sommer, Sarah and Mrisho, Latifa and Legg, James and Adams, Ian P. and Gutierrez-Vazquez, Yaiza and Howard, Thomas P. and Laverick, Alex and et al.}, year={2021}, pages={275–287} } @article{li_liu_hossain_paul_yao_wu_ristaino_zhu_wei_2021, title={Real-time monitoring of plant stresses via chemiresistive profiling of leaf volatiles by a wearable sensor}, volume={4}, ISSN={["2590-2385"]}, DOI={10.1016/j.matt.2021.06.009}, abstractNote={Determination of plant stresses such as infections by plant pathogens is currently dependent on time-consuming and complicated analytical technologies. Here, we report a leaf-attachable chemiresistive sensor array for real-time fingerprinting of volatile organic compounds (VOCs) that permits noninvasive and early diagnosis of plant diseases, such as late blight caused by Phytophthora infestans. The imperceptible sensor patch integrates an array of graphene-based sensing materials and flexible silver nanowire electrodes on a kirigami-inspired stretchable substrate, which can minimize strain interference. The sensor patch has been mounted on live tomato plants to profile key plant volatiles at low-ppm concentrations with fast response (<20 s). The multiplexed sensor array allows for accurate detection and classification of 13 individual plant volatiles with >97% classification accuracy. The wearable sensor patch was used to diagnose tomato late blight as early as 4 days post inoculation and abiotic stresses such as mechanical damage within 1 h.}, number={7}, journal={MATTER}, author={Li, Zheng and Liu, Yuxuan and Hossain, Oindrila and Paul, Rajesh and Yao, Shanshan and Wu, Shuang and Ristaino, Jean B. and Zhu, Yong and Wei, Qingshan}, year={2021}, month={Jul}, pages={2553–2570} } @article{stanciu_wei_barui_mohammad_2021, title={Recent Advances in Aptamer-Based Biosensors for Global Health Applications}, volume={23}, ISSN={["1545-4274"]}, DOI={10.1146/annurev-bioeng-082020-035644}, abstractNote={ Since aptamers were first reported in the early 2000s, research on their use for the detection of health-relevant analytical targets has exploded. This review article provides a brief overview of the most recent developments in the field of aptamer-based biosensors for global health applications. The review provides a description of general aptasensing principles and follows up with examples of recent reports of diagnostics-related applications. These applications include detection of proteins and small molecules, circulating cancer cells, whole-cell pathogens, extracellular vesicles, and tissue diagnostics. The review also discusses the main challenges that this growing technology faces in the quest of bringing these new devices from the laboratory to the market. }, journal={ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 23, 2021}, author={Stanciu, Lia A. and Wei, Qingshan and Barui, Amit K. and Mohammad, Noor}, year={2021}, pages={433–459} } @misc{wang_zhang_wei_2021, title={Smartphone videoscopy: Recent progress and opportunities for biosensing}, volume={10}, ISSN={["2192-8584"]}, url={https://doi.org/10.1515/aot-2021-0009}, DOI={10.1515/aot-2021-0009}, abstractNote={Abstract}, number={2}, journal={ADVANCED OPTICAL TECHNOLOGIES}, publisher={Walter de Gruyter GmbH}, author={Wang, Yan and Zhang, Shengwei and Wei, Qingshan}, year={2021}, month={Apr}, pages={123–138} } @article{ristaino_anderson_bebber_brauman_cunniffe_fedoroff_finegold_garrett_gilligan_jones_et al._2021, title={The persistent threat of emerging plant disease pandemics to global food security}, volume={118}, ISSN={["0027-8424"]}, url={https://doi.org/10.1073/pnas.2022239118}, DOI={10.1073/pnas.2022239118}, abstractNote={Plant disease outbreaks are increasing and threaten food security for the vulnerable in many areas of the world. Now a global human pandemic is threatening the health of millions on our planet. A stable, nutritious food supply will be needed to lift people out of poverty and improve health outcomes. Plant diseases, both endemic and recently emerging, are spreading and exacerbated by climate change, transmission with global food trade networks, pathogen spillover, and evolution of new pathogen lineages. In order to tackle these grand challenges, a new set of tools that include disease surveillance and improved detection technologies including pathogen sensors and predictive modeling and data analytics are needed to prevent future outbreaks. Herein, we describe an integrated research agenda that could help mitigate future plant disease pandemics.}, number={23}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, publisher={Proceedings of the National Academy of Sciences}, author={Ristaino, Jean B. and Anderson, Pamela K. and Bebber, Daniel P. and Brauman, Kate A. and Cunniffe, Nik J. and Fedoroff, Nina V and Finegold, Cambria and Garrett, Karen A. and Gilligan, Christopher A. and Jones, Christopher M. and et al.}, year={2021}, month={Jun} } @misc{tholl_hossain_weinhold_rose_wei_2021, title={Trends and applications in plant volatile sampling and analysis}, volume={106}, ISSN={["1365-313X"]}, DOI={10.1111/tpj.15176}, abstractNote={SUMMARY}, number={2}, journal={PLANT JOURNAL}, author={Tholl, Dorothea and Hossain, Oindrila and Weinhold, Alexander and Rose, Ursula S. R. and Wei, Qingshan}, year={2021}, month={Apr}, pages={314–325} } @article{paul_ostermann_wei_2020, title={Advances in point-of-care nucleic acid extraction technologies for rapid diagnosis of human and plant diseases}, volume={169}, ISSN={["1873-4235"]}, DOI={10.1016/j.bios.2020.112592}, abstractNote={Global health and food security constantly face the challenge of emerging human and plant diseases caused by bacteria, viruses, fungi, and other pathogens. Disease outbreaks such as SARS, MERS, Swine Flu, Ebola, and COVID-19 (on-going) have caused suffering, death, and economic losses worldwide. To prevent the spread of disease and protect human populations, rapid point-of-care (POC) molecular diagnosis of human and plant diseases play an increasingly crucial role. Nucleic acid-based molecular diagnosis reveals valuable information at the genomic level about the identity of the disease-causing pathogens and their pathogenesis, which help researchers, healthcare professionals, and patients to detect the presence of pathogens, track the spread of disease, and guide treatment more efficiently. A typical nucleic acid-based diagnostic test consists of three major steps: nucleic acid extraction, amplification, and amplicon detection. Among these steps, nucleic acid extraction is the first step of sample preparation, which remains one of the main challenges when converting laboratory molecular assays into POC tests. Sample preparation from human and plant specimens is a time-consuming and multi-step process, which requires well-equipped laboratories and skilled lab personnel. To perform rapid molecular diagnosis in resource-limited settings, simpler and instrument-free nucleic acid extraction techniques are required to improve the speed of field detection with minimal human intervention. This review summarizes the recent advances in POC nucleic acid extraction technologies. In particular, this review focuses on novel devices or methods that have demonstrated applicability and robustness for the isolation of high-quality nucleic acid from complex raw samples, such as human blood, saliva, sputum, nasal swabs, urine, and plant tissues. The integration of these rapid nucleic acid preparation methods with miniaturized assay and sensor technologies would pave the road for the "sample-in-result-out" diagnosis of human and plant diseases, especially in remote or resource-limited settings.}, journal={BIOSENSORS & BIOELECTRONICS}, author={Paul, Rajesh and Ostermann, Emily and Wei, Qingshan}, year={2020}, month={Dec} } @misc{li_yu_paul_fan_yang_wei_2020, title={Agricultural nanodiagnostics for plant diseases: recent advances and challenges}, volume={2}, ISSN={["2516-0230"]}, url={https://doi.org/10.1039/C9NA00724E}, DOI={10.1039/c9na00724e}, abstractNote={Engineered nanomaterials integrated with molecular assays or miniature sensing devices formed a promising nanodiagnostic tool box for plant diseases.}, number={8}, journal={NANOSCALE ADVANCES}, publisher={Royal Society of Chemistry (RSC)}, author={Li, Zheng and Yu, Tao and Paul, Rajesh and Fan, Jingyuan and Yang, Yuming and Wei, Qingshan}, year={2020}, month={Aug}, pages={3083–3094} } @article{ristaino_saville_paul_cooper_wei_2020, title={Detection of Phytophthora infestans by Loop-Mediated Isothermal Amplification, Real-Time LAMP, and Droplet Digital PCR}, volume={104}, ISSN={["1943-7692"]}, DOI={10.1094/PDIS-06-19-1186-RE}, abstractNote={ Phytophthora infestans is the causal agent of potato late blight, a devastating disease of tomato and potato and a threat to global food security. Early detection and intervention is essential for effective management of the pathogen. We developed a loop-mediated isothermal amplification (LAMP) assay for P. infestans and compared this assay to conventional PCR, real-time LAMP, and droplet digital PCR for detection of P. infestans. The LAMP assay was specific for P. infestans on potato and tomato and did not amplify other potato- or tomato-infecting Phytophthora species or other fungal and bacterial pathogens that infect potato and tomato. The detection threshold for SYBR Green LAMP and real-time LAMP read with hydroxynaphthol blue and EvaGreen was 1 pg/µl. In contrast, detection by conventional PCR was 10 pg/µl. Droplet digital PCR had the lowest detection threshold (100 fg/µl). We adapted the LAMP assay using SYBR Green and a mobile reader (mReader) for use in the field. Detection limits were 584 fg/µl for SYBR Green LAMP read on the mReader, which was more sensitive than visualization with the human eye. The mobile platform records geospatial coordinates and data from positive pathogen detections can be directly uploaded to a cloud database. Data can then be integrated into disease surveillance networks. This system will be useful for real-time detection of P. infestans and will improve the timeliness of reports into surveillance systems such as USABlight or EuroBlight. }, number={3}, journal={PLANT DISEASE}, author={Ristaino, Jean B. and Saville, Amanda C. and Paul, Rajesh and Cooper, Donald C. and Wei, Qingshan}, year={2020}, month={Mar}, pages={708–716} } @misc{chen_hu_hu_huang_shi_wei_li_2020, title={Portable Analytical Techniques for Monitoring Volatile Organic Chemicals in Biomanufacturing Processes: Recent Advances and Limitations}, volume={8}, ISSN={["2296-2646"]}, DOI={10.3389/fchem.2020.00837}, abstractNote={It is essential to develop effective analytical techniques for accurate and continuous monitoring of various biomanufacturing processes, such as the production of monoclonal antibodies and vaccines, through sensitive and quantitative detection of characteristic aqueous or gaseous metabolites and other analytes in the cell culture media. A comprehensive summary toward the use of mainstream techniques for bioprocess monitoring is critically reviewed here, which illustrates the instrumental and procedural advances and limitations of several major analytical tools in biomanufacturing applications. Despite those drawbacks present in modern detection systems such as mass spectrometry, gas chromatography or chemical/biological sensors, a considerable number of useful solutions and inspirations such as electronic or optoelectronic noses can be offered to greatly overcome the restrictions and facilitate the development of advanced analytical techniques that can target a more diverse range of key nutritious components, products or potential contaminants in different biomanufacturing processes.}, journal={FRONTIERS IN CHEMISTRY}, author={Chen, Xiaofeng and Hu, Runmen and Hu, Luoyu and Huang, Yingcan and Shi, Wenyang and Wei, Qingshan and Li, Zheng}, year={2020}, month={Sep} } @article{li_zhang_yu_dai_wei_2019, title={Aptamer-Based Fluorescent Sensor Array for Multiplexed Detection of Cyanotoxins on a Smartphone}, volume={91}, ISSN={["1520-6882"]}, url={https://doi.org/10.1021/acs.analchem.9b00750}, DOI={10.1021/acs.analchem.9b00750}, abstractNote={Developing easy-to-use and miniaturized detectors is essential for in-field monitoring of environmentally hazardous substances, such as the cyanotoxins. We demonstrated a differential fluorescent sensor array made of aptamers and single-stranded DNA (ssDNA) dyes for multiplexed detection and discrimination of four common cyanotoxins with an ordinary smartphone within 5 minutes of reaction. The assay reagents were preloaded and dried in a microfluidic chip with a long shelf-life over 60 days. Upon the addition of analyte solutions, competitive binding of cyanotoxin to the specific aptamer-dye conjugate occurred. A zone-specific and concentration-dependent reduction in the green fluorescence was observed as a result of the aptamer conformation change. The aptasensors are fully optimized by quantification of their dissociation constants, tuning the stoichiometric ratios of reaction mixtures, and implementation of an internal intensity correction step. The fluorescent sensor array allowed for accurate identification and measurement of four important cyanotoxins, including anatoxin-a (ATX), cylindrospermopsin (CYN), nodularin (NOD), and microcystin-LR (MC-LR), in parallel, with the limit of detection (LOD) down to a few nanomolar (< 3 nM), which is close to the World Health Organization's guideline for the maximum concentration allowed in drinking water. The smartphone-based sensor platform also showed remarkable chemical specificity against potential interfering agents in water. The performance of the system was tested and validated with real lake water samples which were contaminated with trace levels of individual cyano-toxins as well as binary, ternary, and quaternary mixtures. Finally, a smartphone app interface has been developed for rapid on-site data processing and result display.}, number={16}, journal={ANALYTICAL CHEMISTRY}, publisher={American Chemical Society (ACS)}, author={Li, Zheng and Zhang, Shengwei and Yu, Tao and Dai, Zhiming and Wei, Qingshan}, year={2019}, month={Aug}, pages={10448–10457} } @article{vietz_schuette_wei_richter_lalkens_ozcan_tinnefeld_acuna_2019, title={Benchmarking Smartphone Fluorescence-Based Microscopy with DNA Origami Nanobeads: Reducing the Gap toward Single-Molecule Sensitivity}, volume={4}, ISSN={["2470-1343"]}, url={https://doi.org/10.1021/acsomega.8b03136}, DOI={10.1021/acsomega.8b03136}, abstractNote={Smartphone-based fluorescence microscopy has been rapidly developing over the last few years, enabling point-of-need detection of cells, bacteria, viruses, and biomarkers. These mobile microscopy devices are cost-effective, field-portable, and easy to use, and benefit from economies of scale. Recent developments in smartphone camera technology have improved their performance, getting closer to that of lab microscopes. Here, we report the use of DNA origami nanobeads with predefined numbers of fluorophores to quantify the sensitivity of a smartphone-based fluorescence microscope in terms of the minimum number of detectable molecules per diffraction-limited spot. With the brightness of a single dye molecule as a reference, we compare the performance of color and monochrome sensors embedded in state-of-the-art smartphones. Our results show that the monochrome sensor of a smartphone can achieve better sensitivity, with a detection limit of ∼10 fluorophores per spot. The use of DNA origami nanobeads to quantify the minimum number of detectable molecules of a sensor is broadly applicable to evaluate the sensitivity of various optical instruments.}, number={1}, journal={ACS OMEGA}, publisher={American Chemical Society (ACS)}, author={Vietz, Carolin and Schuette, Max L. and Wei, Qingshan and Richter, Lars and Lalkens, Birka and Ozcan, Aydogan and Tinnefeld, Philip and Acuna, Guillermo P.}, year={2019}, month={Jan}, pages={637–642} } @article{wu_ray_wei_feizi_tong_chen_luo_ozcan_2019, title={Deep Learning Enables High-Throughput Analysis of Particle-Aggregation-Based Biosensors Imaged Using Holography}, volume={6}, ISSN={["2330-4022"]}, url={https://doi.org/10.1021/acsphotonics.8b01479}, DOI={10.1021/acsphotonics.8b01479}, abstractNote={Aggregation-based assays, using micro- and nanoparticles have been widely accepted as an efficient and cost-effective biosensing tool, particularly in microbiology, where particle clustering events are used as a metric to infer the presence of a specific target analyte and quantify its concentration. Here, we present a sensitive and automated readout method for aggregation-based assays using a wide-field lens-free on-chip microscope, with the ability to rapidly analyze and quantify microscopic particle aggregation events in 3D, using deep learning-based holographic image reconstruction. In this method, the computation time for hologram reconstruction and particle autofocusing steps remains constant, regardless of the number of particles/clusters within the 3D sample volume, which provides a major throughput advantage, brought by deep learning-based image reconstruction. As a proof of concept, we demonstrate rapid detection of herpes simplex virus (HSV) by monitoring the clustering of antibody-coated micro...}, number={2}, journal={ACS PHOTONICS}, publisher={American Chemical Society (ACS)}, author={Wu, Yichen and Ray, Aniruddha and Wei, Qingshan and Feizi, Alborz and Tong, Xin and Chen, Eva and Luo, Yi and Ozcan, Aydogan}, year={2019}, month={Feb}, pages={294–301} } @article{paul_saville_hansel_ye_ball_williams_chang_chen_gu_ristaino_et al._2019, title={Extraction of Plant DNA by Microneedle Patch for Rapid Detection of Plant Diseases}, volume={13}, ISSN={1936-0851 1936-086X}, url={http://dx.doi.org/10.1021/acsnano.9b00193}, DOI={10.1021/acsnano.9b00193}, abstractNote={In-field molecular diagnosis of plant diseases via nucleic acid amplification is currently limited by cumbersome protocols for extracting and isolating pathogenic DNA from plant tissues. To address this challenge, a rapid plant DNA extraction method was developed using a disposable polymeric microneedle (MN) patch. By applying MN patches on plant leaves, amplification-assay-ready DNA can be extracted within a minute from different plant species. MN-extracted DNA was used for direct polymerase chain reaction amplification of plant plastid DNA without purification. Furthermore, using this patch device, extraction of plant pathogen DNA ( Phytophthora infestans) from both laboratory-inoculated and field-infected leaf samples was performed for detection of late blight disease in tomato. MN extraction achieved 100% detection rate of late blight infections for samples after 3 days of inoculation when compared to the conventional gold standard cetyltrimethylammonium bromide (CTAB)-based DNA extraction method and 100% detection rate for all blind field samples tested. This simple, cell-lysis-free, and purification-free DNA extraction method could be a transformative approach to facilitate rapid sample preparation for molecular diagnosis of various plant diseases directly in the field.}, number={6}, journal={ACS Nano}, publisher={American Chemical Society (ACS)}, author={Paul, Rajesh and Saville, Amanda C. and Hansel, Jeana C. and Ye, Yanqi and Ball, Carmin and Williams, Alyssa and Chang, Xinyuan and Chen, Guojun and Gu, Zhen and Ristaino, Jean B. and et al.}, year={2019}, month={Jun}, pages={6540–6549} } @article{li_paul_tis_saville_hansel_yu_ristaino_wei_2019, title={Non-invasive plant disease diagnostics enabled by smartphone-based fingerprinting of leaf volatiles}, url={https://doi.org/10.1038/s41477-019-0476-y}, DOI={10.1038/s41477-019-0476-y}, abstractNote={Plant pathogen detection conventionally relies on molecular technology that is complicated, time-consuming and constrained to centralized laboratories. We developed a cost-effective smartphone-based volatile organic compound (VOC) fingerprinting platform that allows non-invasive diagnosis of late blight caused by Phytophthora infestans by monitoring characteristic leaf volatile emissions in the field. This handheld device integrates a disposable colourimetric sensor array consisting of plasmonic nanocolorants and chemo-responsive organic dyes to detect key plant volatiles at the ppm level within 1 min of reaction. We demonstrate the multiplexed detection and classification of ten individual plant volatiles with this field-portable VOC-sensing platform, which allows for early detection of tomato late blight 2 d after inoculation, and differentiation from other pathogens of tomato that lead to similar symptoms on tomato foliage. Furthermore, we demonstrate a detection accuracy of ≥95% in diagnosis of P. infestans in both laboratory-inoculated and field-collected tomato leaves in blind pilot tests. Finally, the sensor platform has been beta-tested for detection of P. infestans in symptomless tomato plants in the greenhouse setting.}, journal={Nature Plants}, author={Li, Zheng and Paul, Rajesh and Tis, Taleb Ba and Saville, Amanda C. and Hansel, Jeana C. and Yu, Tao and Ristaino, Jean B. and Wei, Qingshan}, year={2019}, month={Jul} } @misc{hernandez-neuta_neumann_brightmeyer_tis_madaboosi_wei_ozcan_nilsson_2019, title={Smartphone-based clinical diagnostics: towards democratization of evidence-based health care}, volume={285}, ISSN={["1365-2796"]}, url={https://doi.org/10.1111/joim.12820}, DOI={10.1111/joim.12820}, abstractNote={Abstract}, number={1}, journal={JOURNAL OF INTERNAL MEDICINE}, author={Hernandez-Neuta, I. and Neumann, F. and Brightmeyer, J. and Tis, T. Ba and Madaboosi, N. and Wei, Q. and Ozcan, A. and Nilsson, M.}, year={2019}, month={Jan}, pages={19–39} } @article{kim_wei_kim_tseng_zhang_pan_garner_ozcan_di carlo_2018, title={Enzyme-Free Nucleic Acid Amplification Assay Using a Cellphone-Based Well Plate Fluorescence Reader}, volume={90}, ISSN={["1520-6882"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85040172212&partnerID=MN8TOARS}, DOI={10.1021/acs.analchem.7b03848}, abstractNote={Nucleic acids, DNA and RNA, provide important fingerprint information for various pathogens and have significant diagnostic value; however, improved approaches are urgently needed to enable rapid detection of nucleic acids in simple point-of-care formats with high sensitivity and specificity. Here, we present a system that utilizes a series of toehold-triggered hybridization/displacement reactions that are designed to convert a given amount of RNA molecules (i.e., the analyte) into an amplified amount of signaling molecules without any washing steps or thermocycling. Fluorescent probes for signal generation were designed to consume products of the catalytic reaction in order to push the equilibrium and enhance the assay fold amplification for improved sensitivity and reaction speed. The system of toehold-assisted reactions is also modeled to better understand its performance and capabilities, and we empirically demonstrate the success of this approach with two analytes of diagnostic importance, i.e., influenza viral RNA and a micro RNA (miR-31). We also show that the amplified signal permits using a compact and cost-effective smartphone-based fluorescence reader, an important requirement toward a nucleic-acid-based point-of-care diagnostic system.}, number={1}, journal={ANALYTICAL CHEMISTRY}, author={Kim, Donghyuk and Wei, Qingshan and Kim, Dong Hyeok and Tseng, Derek and Zhang, Jingzi and Pan, Eric and Garner, Omai and Ozcan, Aydogan and Di Carlo, Dino}, year={2018}, month={Jan}, pages={690–695} } @article{kahkeshani_kong_wei_tseng_garner_ozcan_di carlo_2018, title={Ferrodrop Dose-Optimized Digital Quantification of Biomolecules in Low-Volume Samples}, volume={90}, ISSN={0003-2700 1520-6882}, url={http://dx.doi.org/10.1021/ACS.ANALCHEM.8B00958}, DOI={10.1021/ACS.ANALCHEM.8B00958}, abstractNote={We present an approach to estimate the concentration of a biomolecule in a solution by sampling several nanoliter-scale volumes and determining if the volumes contain any biomolecules. In this method, varying volume fractions (nanoliter-scale) of a sample of nucleic acids are introduced to an array of uniform volume reaction wells (100 μL), which are then fluorescently imaged to determine if signal is above a threshold after nucleic acid amplification, all without complex instrumentation. The nanoliter volumes are generated and introduced using the simple positioning of a permanent magnet, and imaging is performed with a cellphone-based fluorescence detection scheme, both methods suitable for limited-resource settings. We use the length of time a magnetic field is applied to generate a calibrated number of nanoliter ferrodrops of sample mixed with ferrofluid at a step emulsification microfluidic junction. Each dose of ferrodrops is then transferred into larger microliter scale reaction wells on chip through a simple shift of the external magnet. Nucleic acid amplification is achieved using loop-mediated isothermal amplification (LAMP). By repeating each nanoliter dosage a number of times to calculate the probability of a positive signal at each dosage, we can use a binomial probability distribution to estimate the sample nucleic acid concentration. Using this approach we demonstrate detection of lambda DNA molecules down to 25 copies per microliter. The ability to dose separate nanoliter-scale volumes of a low-volume sample across wells in this platform is suited for multiplexed assays. This platform has the potential to be applied to a range of diseases by mixing a sample with magnetic nanoparticles.}, number={15}, journal={Analytical Chemistry}, publisher={American Chemical Society (ACS)}, author={Kahkeshani, Soroush and Kong, Janay E. and Wei, Qingshan and Tseng, Derek and Garner, Omai B. and Ozcan, Aydogan and Di Carlo, Dino}, year={2018}, month={Jul}, pages={8881–8888} } @misc{yu_wei_2018, title={Plasmonic molecular assays: Recent advances and applications for mobile health}, volume={11}, ISSN={["1998-0000"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85048056782&partnerID=MN8TOARS}, DOI={10.1007/s12274-018-2094-9}, abstractNote={Plasmonics-based biosensing assays have been extensively employed for biomedical applications. Significant advancements in use of plasmonic assays for the construction of point-of-care (POC) diagnostic methods have been made to provide effective and urgent health care of patients, especially in resourcelimited settings. This rapidly progressive research area, centered on the unique surface plasmon resonance (SPR) properties of metallic nanostructures with exceptional absorption and scattering abilities, has greatly facilitated the development of cost-effective, sensitive, and rapid strategies for disease diagnostics and improving patient healthcare in both developed and developing worlds. This review highlights the recent advances and applications of plasmonic technologies for highly sensitive protein and nucleic acid biomarker detection. In particular, we focus on the implementation and penetration of various plasmonic technologies in conventional molecular diagnostic assays, and discuss how such modification has resulted in simpler, faster, and more sensitive alternatives that are suited for point-of-use. Finally, integration of plasmonic molecular assays with various portable POC platforms for mobile health applications are highlighted.}, number={10}, journal={NANO RESEARCH}, publisher={Springer Nature}, author={Yu, Tao and Wei, Qingshan}, year={2018}, month={Oct}, pages={5439–5473} } @inproceedings{wei_acuna_kim_vietz_tseng_chae_shir_luo_tinnefeld_ozcan_2018, title={Plasmonics Improves the Sensitivity of Smartphone Fluorescence Microscopy}, DOI={10.1364/cleo_at.2018.am1j.4}, abstractNote={We developed a handheld and cost-effective surface-enhanced smartphone fluorescence microscope that showed ~10-fold improvement in signal by using a thin silver film as a plasmonic substrate, enabling the detection of ~80 fluorophores per diffraction-limited spot.}, booktitle={Conference on Lasers and Electro-Optics}, publisher={OSA}, author={Wei, Qingshan and Acuna, Guillermo and Kim, Seungkyeum and Vietz, Carolin and Tseng, Derek and Chae, Jongjae and Shir, Daniel and Luo, Wei and Tinnefeld, Philip and Ozcan, Aydogan}, year={2018} } @article{kong_wei_tseng_zhang_pan_lewinski_garner_ozcan_di carlo_2017, title={Highly Stable and Sensitive Nucleic Acid Amplification and Cell-Phone-Based Readout}, volume={11}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85016391164&partnerID=MN8TOARS}, DOI={10.1021/acsnano.6b08274}, abstractNote={Key challenges with point-of-care (POC) nucleic acid tests include achieving a low-cost, portable form factor, and stable readout, while also retaining the same robust standards of benchtop lab-based tests. We addressed two crucial aspects of this problem, identifying a chemical additive, hydroxynaphthol blue, that both stabilizes and significantly enhances intercalator-based fluorescence readout of nucleic acid concentration, and developing a cost-effective fiber-optic bundle-based fluorescence microplate reader integrated onto a mobile phone. Using loop-mediated isothermal amplification on lambda DNA we achieve a 69-fold increase in signal above background, 20-fold higher than the gold standard, yielding an overall limit of detection of 25 copies/μL within an hour using our mobile-phone-based platform. Critical for a point-of-care system, we achieve a >60% increase in fluorescence stability as a function of temperature and time, obviating the need for manual baseline correction or secondary calibration dyes. This field-portable and cost-effective mobile-phone-based nucleic acid amplification and readout platform is broadly applicable to other real-time nucleic acid amplification tests by similarly modulating intercalating dye performance and is compatible with any fluorescence-based assay that can be run in a 96-well microplate format, making it especially valuable for POC and resource-limited settings.}, number={3}, journal={ACS Nano}, author={Kong, J.E. and Wei, Q. and Tseng, D. and Zhang, J. and Pan, E. and Lewinski, M. and Garner, O.B. and Ozcan, A. and Di Carlo, D.}, year={2017}, pages={2934–2943} } @article{joh_hucknall_wei_mason_lund_fontes_hill_blair_zimmers_achar_et al._2017, title={Inkjet-printed point-of-care immunoassay on a nanoscale polymer brush enables subpicomolar detection of analytes in blood}, volume={114}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85027880366&partnerID=MN8TOARS}, DOI={10.1073/pnas.1703200114}, abstractNote={Significance}, number={34}, journal={Proceedings of the National Academy of Sciences of the United States of America}, author={Joh, D.Y. and Hucknall, A.M. and Wei, Q. and Mason, K.A. and Lund, M.L. and Fontes, C.M. and Hill, R.T. and Blair, R. and Zimmers, Z. and Achar, R.K. and et al.}, year={2017}, pages={E7054–E7062} } @article{wei_acuna_kim_vietz_tseng_chae_shir_luo_tinnefeld_ozcan_et al._2017, title={Plasmonics Enhanced Smartphone Fluorescence Microscopy}, volume={7}, ISSN={["2045-2322"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85019862681&partnerID=MN8TOARS}, DOI={10.1038/s41598-017-02395-8}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, publisher={Springer Nature}, author={Wei, Qingshan and Acuna, Guillermo and Kim, Seungkyeum and Vietz, Carolin and Tseng, Derek and Chae, Jongjae and Shir, Daniel and Luo, Wei and Tinnefeld, Philip and Ozcan, Aydogan and et al.}, year={2017}, month={May} } @article{kühnemund_wei_darai_wang_iván_yang_tseng_ahlford_mathot_sjöblom_et al._2017, title={Targeted DNA sequencing and in situ mutation analysis using mobile phone microscopy}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85009909976&partnerID=MN8TOARS}, DOI={10.1038/ncomms13913}, abstractNote={Abstract}, journal={Nature Communications}, author={Kühnemund, M. and Wei, Q. and Darai, E. and Wang, Y. and Iván, H.-N. and Yang, Z. and Tseng, D. and Ahlford, A. and Mathot, L. and Sjöblom, T. and et al.}, year={2017} } @inproceedings{berg_cortazar_tseng_ozkan_feng_wei_chan_burbano_farooqui_lewinski_et al._2016, title={A smartphone-based microplate reader for point-of-care ELISA quantification}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85010702301&partnerID=MN8TOARS}, booktitle={2016 Conference on Lasers and Electro-Optics, CLEO 2016}, author={Berg, B. and Cortazar, B. and Tseng, D. and Ozkan, H. and Feng, S. and Wei, Q. and Chan, R.Y.-L. and Burbano, J. and Farooqui, Q. and Lewinski, M. and et al.}, year={2016} } @article{contreras-naranjo_wei_ozcan_2016, title={Mobile Phone-Based Microscopy, Sensing, and Diagnostics}, volume={22}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84963668271&partnerID=MN8TOARS}, DOI={10.1109/JSTQE.2015.2478657}, abstractNote={Mass production of consumer electronics devices and market competition have provided users with cost-effective, compact, and high-performance products with high-end components including digital cameras, graphics processing units, and various sensors. This opened up the opportunity for researchers, and even citizen scientists, to develop novel imaging, sensing, and diagnostics platforms using mobile phones as an underlying platform. Mobile phones' hardware and software technical capabilities, wireless connectivity, and wide-spread use, in billions, have made them ideal, especially to address the global demand for accurate, sensitive, cost-effective, and field-portable measurement devices that can be used in remote and resource-limited settings around the world. This Review focuses on these recent advances in the use of mobile phone-based imaging and sensing techniques for point of care applications, including microscopy and diagnostic testing. The achievements demonstrated so far illustrate the potential to globally transform and democratize measurement science in general, with a significant impact for scientists, engineers, and educators.}, number={3}, journal={IEEE Journal on Selected Topics in Quantum Electronics}, author={Contreras-Naranjo, J.C. and Wei, Q. and Ozcan, A.}, year={2016} } @inproceedings{wei_luo_chiang_kappel_mejia_tseng_chan_yan_qi_shabbir_et al._2016, title={Single DNA imaging and length quantification through a mobile phone microscope}, volume={9699}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84973484048&partnerID=MN8TOARS}, DOI={10.1117/12.2208836}, abstractNote={The development of sensitive optical microscopy methods for the detection of single DNA molecules has become an active research area which cultivates various promising applications including point-of-care (POC) genetic testing and diagnostics. Direct visualization of individual DNA molecules usually relies on sophisticated optical microscopes that are mostly available in well-equipped laboratories. For POC DNA testing/detection, there is an increasing need for the development of new single DNA imaging and sensing methods that are field-portable, cost-effective, and accessible for diagnostic applications in resource-limited or field-settings. For this aim, we developed a mobile-phone integrated fluorescence microscopy platform that allows imaging and sizing of single DNA molecules that are stretched on a chip. This handheld device contains an opto-mechanical attachment integrated onto a smartphone camera module, which creates a high signal-to-noise ratio dark-field imaging condition by using an oblique illumination/excitation configuration. Using this device, we demonstrated imaging of individual linearly stretched λ DNA molecules (48 kilobase-pair, kbp) over 2 mm2 field-of-view. We further developed a robust computational algorithm and a smartphone app that allowed the users to quickly quantify the length of each DNA fragment imaged using this mobile interface. The cellphone based device was tested by five different DNA samples (5, 10, 20, 40, and 48 kbp), and a sizing accuracy of <1 kbp was demonstrated for DNA strands longer than 10 kbp. This mobile DNA imaging and sizing platform can be very useful for various diagnostic applications including the detection of disease-specific genes and quantification of copy-number-variations at POC settings.}, booktitle={Progress in Biomedical Optics and Imaging - Proceedings of SPIE}, author={Wei, Q. and Luo, W. and Chiang, S. and Kappel, T. and Mejia, C. and Tseng, D. and Chan, R.Y.L. and Yan, E. and Qi, H. and Shabbir, F. and et al.}, year={2016} } @article{berg_cortazar_tseng_ozkan_feng_wei_chan_burbano_farooqui_lewinski_et al._2015, title={Cellphone-Based Hand-Held Microplate Reader for Point-of-Care Testing of Enzyme-Linked Immunosorbent Assays}, volume={9}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84940055719&partnerID=MN8TOARS}, DOI={10.1021/acsnano.5b03203}, abstractNote={Standard microplate based enzyme-linked immunosorbent assays (ELISA) are widely utilized for various nanomedicine, molecular sensing, and disease screening applications, and this multiwell plate batched analysis dramatically reduces diagnosis costs per patient compared to nonbatched or nonstandard tests. However, their use in resource-limited and field-settings is inhibited by the necessity for relatively large and expensive readout instruments. To mitigate this problem, we created a hand-held and cost-effective cellphone-based colorimetric microplate reader, which uses a 3D-printed opto-mechanical attachment to hold and illuminate a 96-well plate using a light-emitting-diode (LED) array. This LED light is transmitted through each well, and is then collected via 96 individual optical fibers. Captured images of this fiber-bundle are transmitted to our servers through a custom-designed app for processing using a machine learning algorithm, yielding diagnostic results, which are delivered to the user within ∼1 min per 96-well plate, and are visualized using the same app. We successfully tested this mobile platform in a clinical microbiology laboratory using FDA-approved mumps IgG, measles IgG, and herpes simplex virus IgG (HSV-1 and HSV-2) ELISA tests using a total of 567 and 571 patient samples for training and blind testing, respectively, and achieved an accuracy of 99.6%, 98.6%, 99.4%, and 99.4% for mumps, measles, HSV-1, and HSV-2 tests, respectively. This cost-effective and hand-held platform could assist health-care professionals to perform high-throughput disease screening or tracking of vaccination campaigns at the point-of-care, even in resource-poor and field-settings. Also, its intrinsic wireless connectivity can serve epidemiological studies, generating spatiotemporal maps of disease prevalence and immunity.}, number={8}, journal={ACS Nano}, author={Berg, B. and Cortazar, B. and Tseng, D. and Ozkan, H. and Feng, S. and Wei, Q. and Chan, R.Y.-L. and Burbano, J. and Farooqui, Q. and Lewinski, M. and et al.}, year={2015}, pages={7857–7866} } @article{mcleod_wei_ozcan_2015, title={Democratization of Nanoscale Imaging and Sensing Tools Using Photonics}, volume={87}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84936797639&partnerID=MN8TOARS}, DOI={10.1021/acs.analchem.5b01381}, abstractNote={Providing means for researchers and citizen scientists in the developing world to perform advanced measurements with nanoscale precision can help to accelerate the rate of discovery and invention as well as improve higher education and the training of the next generation of scientists and engineers worldwide. Here, we review some of the recent progress toward making optical nanoscale measurement tools more cost-effective, field-portable, and accessible to a significantly larger group of researchers and educators. We divide our review into two main sections: label-based nanoscale imaging and sensing tools, which primarily involve fluorescent approaches, and label-free nanoscale measurement tools, which include light scattering sensors, interferometric methods, photonic crystal sensors, and plasmonic sensors. For each of these areas, we have primarily focused on approaches that have either demonstrated operation outside of a traditional laboratory setting, including for example integration with mobile phones, or exhibited the potential for such operation in the near future.}, number={13}, journal={Analytical Chemistry}, author={McLeod, E. and Wei, Q. and Ozcan, A.}, year={2015}, pages={6434–6445} } @inproceedings{wei_luo_chiang_kappe_mejia_tseng_yan_chan_yan_qi_et al._2015, title={Field-portable smartphone microscopy platform for widefield imaging and sizing of single DNA molecules}, volume={2015-August}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84935040614&partnerID=MN8TOARS}, DOI={10.1364/CLEO_AT.2015.ATh4J.6}, abstractNote={We demonstrate a field-portable smartphone-based fluorescence microscopy platform for imaging and sizing of single DNA molecules across ~2 mm2 field-of-view with <;1 kbp length accuracy.}, booktitle={CLEO: Applications and Technology, CLEO-AT 2015}, author={Wei, Q. and Luo, W. and Chiang, S. and Kappe, T. and Mejia, C. and Tseng, D. and Yan and Chan, L. and Yan, E. and Qi, H. and et al.}, year={2015} } @article{kim_wei_kong_ozcan_carlo_2015, title={Research highlights: digital assays on chip}, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84915763015&partnerID=MN8TOARS}, DOI={10.1039/c4lc90119c}, abstractNote={Digital measurement with a high dynamic range – Are digital nucleic acid assays more robust? – Digital measurement of membrane transporter proteins.}, number={1}, journal={Lab on a Chip}, publisher={Royal Society of Chemistry (RSC)}, author={Kim, Donghyuk and Wei, Qingshan and Kong, Janay Elise and Ozcan, Aydogan and Carlo, Dino Di}, year={2015}, pages={17–22} } @article{wei_nagi_sadeghi_feng_yan_ki_caire_tseng_ozcan_2014, title={Detection and spatial mapping of mercury contamination in water samples using a smart-phone}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84894611120&partnerID=MN8TOARS}, DOI={10.1021/nn406571t}, abstractNote={Detection of environmental contamination such as trace-level toxic heavy metal ions mostly relies on bulky and costly analytical instruments. However, a considerable global need exists for portable, rapid, specific, sensitive, and cost-effective detection techniques that can be used in resource-limited and field settings. Here we introduce a smart-phone-based hand-held platform that allows the quantification of mercury(II) ions in water samples with parts per billion (ppb) level of sensitivity. For this task, we created an integrated opto-mechanical attachment to the built-in camera module of a smart-phone to digitally quantify mercury concentration using a plasmonic gold nanoparticle (Au NP) and aptamer based colorimetric transmission assay that is implemented in disposable test tubes. With this smart-phone attachment that weighs <40 g, we quantified mercury(II) ion concentration in water samples by using a two-color ratiometric method employing light-emitting diodes (LEDs) at 523 and 625 nm, where a custom-developed smart application was utilized to process each acquired transmission image on the same phone to achieve a limit of detection of ∼3.5 ppb. Using this smart-phone-based detection platform, we generated a mercury contamination map by measuring water samples at over 50 locations in California (USA), taken from city tap water sources, rivers, lakes, and beaches. With its cost-effective design, field-portability, and wireless data connectivity, this sensitive and specific heavy metal detection platform running on cellphones could be rather useful for distributed sensing, tracking, and sharing of water contamination information as a function of both space and time.}, number={2}, journal={ACS Nano}, author={Wei, Q. and Nagi, R. and Sadeghi, K. and Feng, S. and Yan, E. and Ki, S.J. and Caire, R. and Tseng, D. and Ozcan, A.}, year={2014}, pages={1121–1129} } @inproceedings{göröcs_ling_yu_karahalios_mogharabi_lu_wei_ozcan_2014, title={Fluorescent imaging over an ultra-large field-of-view of 532 cm2 using a flatbed scanner}, volume={8951}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84897520879&partnerID=MN8TOARS}, DOI={10.1117/12.2038602}, abstractNote={We introduce a fluorescent imaging method that is capable of detecting fluorescent micro-particles over an ultra-wide field of view of 19 cm × 28 cm using a modified flatbed scanner. We added a custom-designed absorbing emission filter, a computer controlled two dimensional LED array, and modified the driver of the scanner to maximize the sensitivity, exposure time, and gain for fluorescent detection of micro-objects. This high-throughput fluorescent imaging device used in conjunction with a microfluidic sample holder enables rapid screening of fluorescent micro-objects inside more than 2.2mL of optically dense media (i.e., whole blood) within 5 minutes. The device is sensitive enough to detect fluorescently labeled cells, and generates images that have an effective pixel count of 2.2 Giga-pixels.}, booktitle={Progress in Biomedical Optics and Imaging - Proceedings of SPIE}, author={Göröcs, Z. and Ling, Y. and Yu, M.D. and Karahalios, D. and Mogharabi, K. and Lu, K. and Wei, Q. and Ozcan, A.}, year={2014} } @article{wei_luo_chiang_kappel_mejia_tseng_chan_yan_qi_shabbir_et al._2014, title={Imaging and sizing of single DNA molecules on a mobile phone}, volume={8}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84919756205&partnerID=MN8TOARS}, DOI={10.1021/nn505821y}, abstractNote={DNA imaging techniques using optical microscopy have found numerous applications in biology, chemistry and physics and are based on relatively expensive, bulky and complicated set-ups that limit their use to advanced laboratory settings. Here we demonstrate imaging and length quantification of single molecule DNA strands using a compact, lightweight and cost-effective fluorescence microscope installed on a mobile phone. In addition to an optomechanical attachment that creates a high contrast dark-field imaging setup using an external lens, thin-film interference filters, a miniature dovetail stage and a laser-diode for oblique-angle excitation, we also created a computational framework and a mobile phone application connected to a server back-end for measurement of the lengths of individual DNA molecules that are labeled and stretched using disposable chips. Using this mobile phone platform, we imaged single DNA molecules of various lengths to demonstrate a sizing accuracy of <1 kilobase-pairs (kbp) for 10 kbp and longer DNA samples imaged over a field-of-view of ∼2 mm2.}, number={12}, journal={ACS Nano}, author={Wei, Q. and Luo, W. and Chiang, S. and Kappel, T. and Mejia, C. and Tseng, D. and Chan, R.Y.L. and Yan, E. and Qi, H. and Shabbir, F. and et al.}, year={2014}, pages={12725–12733} } @article{stensberg_madangopal_yale_wei_ochoa-acuna_wei_mclamore_rickus_porterfield_sepulveda_2014, title={Silver nanoparticle-specific mitotoxicity in Daphnia magna}, volume={8}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000328131000003&KeyUID=WOS:000328131000003}, DOI={10.3109/17435390.2013.832430}, abstractNote={Abstract Silver nanoparticles (Ag NPs) are gaining popularity as bactericidal agents in commercial products; however, the mechanisms of toxicity (MOT) of Ag NPs to other organisms are not fully understood. It is the goal of this research to determine differences in MOT induced by ionic Ag+ and Ag NPs in Daphnia magna, by incorporating a battery of traditional and novel methods. Daphnia embryos were exposed to sublethal concentrations of AgNO3 and Ag NPs (130–650 ng/L), with uptake of the latter confirmed by confocal reflectance microscopy. Mitochondrial function was non-invasively monitored by measuring proton flux using self-referencing microsensors. Proton flux measurements revealed that while both forms of silver significantly affected proton efflux, the change induced by Ag NPs was greater than that of Ag+. This could be correlated with the effects of Ag NPs on mitochondrial dysfunction, as determined by confocal fluorescence microscopy and JC-1, an indicator of mitochondrial permeability. However, Ag+ was more efficient than Ag NPs at displacing Na+ within embryonic Daphnia, based on inductively coupled plasma-mass spectroscopy (ICP-MS) analysis. The abnormalities in mitochondrial activity for Ag NP-exposed organisms suggest a nanoparticle-specific MOT, distinct from that induced by Ag ions. We propose that the MOT of each form of silver are complementary, and can act in synergy to produce a greater toxic response overall.}, number={8}, journal={Nanotoxicology}, author={Stensberg, M. C. and Madangopal, R. and Yale, G. and Wei, Q. S. and Ochoa-Acuna, H. and Wei, A. and McLamore, E. S. and Rickus, J. and Porterfield, D. M. and Sepulveda, M. S.}, year={2014}, pages={833–842} } @inproceedings{wei_qi_luo_tseng_bentolila_wu_sun_ozcan_2014, title={Single Nanoparticle and Virus Detection Using a Smart Phone Based Fluorescence Microscope}, volume={2014-January}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84905369899&partnerID=MN8TOARS}, booktitle={Optics InfoBase Conference Papers}, author={Wei, Q. and Qi, H. and Luo, W. and Tseng, D. and Bentolila, L.A. and Wu, T.-T. and Sun, R. and Ozcan, A.}, year={2014} } @article{wei_qi_luo_tseng_ki_wan_gorocs_bentolila_wu_sun_et al._2013, title={Fluorescent Imaging of Single Nanoparticles and Viruses on a Smart Phone}, volume={7}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000326209100088&KeyUID=WOS:000326209100088}, DOI={10.1021/nn4037706}, abstractNote={Optical imaging of nanoscale objects, whether it is based on scattering or fluorescence, is a challenging task due to reduced detection signal-to-noise ratio and contrast at subwavelength dimensions. Here, we report a field-portable fluorescence microscopy platform installed on a smart phone for imaging of individual nanoparticles as well as viruses using a lightweight and compact opto-mechanical attachment to the existing camera module of the cell phone. This hand-held fluorescent imaging device utilizes (i) a compact 450 nm laser diode that creates oblique excitation on the sample plane with an incidence angle of ~75°, (ii) a long-pass thin-film interference filter to reject the scattered excitation light, (iii) an external lens creating 2× optical magnification, and (iv) a translation stage for focus adjustment. We tested the imaging performance of this smart-phone-enabled microscopy platform by detecting isolated 100 nm fluorescent particles as well as individual human cytomegaloviruses that are fluorescently labeled. The size of each detected nano-object on the cell phone platform was validated using scanning electron microscopy images of the same samples. This field-portable fluorescence microscopy attachment to the cell phone, weighing only ~186 g, could be used for specific and sensitive imaging of subwavelength objects including various bacteria and viruses and, therefore, could provide a valuable platform for the practice of nanotechnology in field settings and for conducting viral load measurements and other biomedical tests even in remote and resource-limited environments.}, number={10}, journal={Acs Nano}, author={Wei, Q. S. and Qi, H. F. and Luo, W. and Tseng, D. and Ki, S. J. and Wan, Z. and Gorocs, Z. and Bentolila, L. A. and Wu, T. T. and Sun, R. and et al.}, year={2013}, pages={9147–9155} } @article{gorocs_ling_yu_karahalios_mogharabi_lu_wei_ozcan_2013, title={Giga-pixel fluorescent imaging over an ultra-large field-of-view using a flatbed scanner}, volume={13}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000325946800024&KeyUID=WOS:000325946800024}, DOI={10.1039/c3lc51005k}, abstractNote={We demonstrate a new fluorescent imaging technique that can screen for fluorescent micro-objects over an ultra-wide field-of-view (FOV) of ~532 cm(2), i.e., 19 cm × 28 cm, reaching a space-bandwidth product of more than 2 billion. For achieving such a large FOV, we modified the hardware and software of a commercially available flatbed scanner, and added a custom-designed absorbing fluorescent filter, a two-dimensional array of external light sources for computer-controlled and high-angle fluorescent excitation. We also re-programmed the driver of the scanner to take full control of the scanner hardware and achieve the highest possible exposure time, gain and sensitivity for detection of fluorescent micro-objects through the gradient index self-focusing lens array that is positioned in front of the scanner sensor chip. For example, this large FOV of our imaging platform allows us to screen more than 2.2 mL of undiluted whole blood for detection of fluorescent micro-objects within <5 minutes. This high-throughput fluorescent imaging platform could be useful for rare cell research and cytometry applications by enabling rapid screening of large volumes of optically dense media. Our results constitute the first time that a flatbed scanner has been converted to a fluorescent imaging system, achieving a record large FOV.}, number={22}, journal={Lab on a Chip}, author={Gorocs, Z. and Ling, Y. Y. and Yu, M. D. and Karahalios, D. and Mogharabi, K. and Lu, K. and Wei, Q. S. and Ozcan, A.}, year={2013}, pages={4460–4466} } @inproceedings{wei_mcleod_qi_wan_sun_ozcan_2013, title={Lensfree holographic cytometry using plasmonic nanoparticles}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84892689806&partnerID=MN8TOARS}, DOI={10.1109/IPCon.2013.6656337}, abstractNote={Cellular contrast was demonstrated for the first time in lensfree on-chip holography by employing antibody-conjugated gold and silver nanoparticles (NPs) as contrast agents. Cytometric differentiation of CD4+ and CD8+ lymphocytes was achieved, after NP labeling, using machine learning algorithms.}, booktitle={2013 IEEE Photonics Conference, IPC 2013}, author={Wei, Q. and McLeod, E. and Qi, H. and Wan, Z. and Sun, R. and Ozcan, A.}, year={2013}, pages={3–4} } @article{wei_mcleod_qi_wan_sun_ozcan_2013, title={On-Chip Cytometry using Plasmonic Nanoparticle Enhanced Lensfree Holography}, volume={3}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000317892500002&KeyUID=WOS:000317892500002}, DOI={10.1038/srep01699}, abstractNote={Computational microscopy tools, in particular lensfree on-chip imaging, provide a large field-of-view along with a long depth-of-field, which makes it feasible to rapidly analyze large volumes of specimen using a compact and light-weight on-chip imaging architecture. To bring molecular specificity to this high-throughput platform, here we demonstrate the use of plasmon-resonant metallic nanoparticles to automatically recognize different cell types based on their plasmon-enhanced lensfree holograms, detected and reconstructed over a large field-of-view of e.g., ~24 mm².}, journal={Scientific Reports}, author={Wei, Q. S. and McLeod, E. and Qi, H. F. and Wan, Z. and Sun, R. and Ozcan, A.}, year={2013} } @article{xia_song_wei_wei_2012, title={Differential response of macrophages to core-shell Fe3O4@Au nanoparticles and nanostars}, volume={4}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000310978100032&KeyUID=WOS:000310978100032}, DOI={10.1039/c2nr32070c}, abstractNote={Murine RAW 264.7 cells were exposed to spheroidal core-shell Fe(3)O(4)@Au nanoparticles (SCS-NPs, ca. 34 nm) or nanostars (NSTs, ca. 100 nm) in the presence of bovine serum albumin, with variable effects observed after macrophagocytosis. Uptake of SCS-NPs caused macrophages to adopt a rounded, amoeboid form, accompanied by an increase in surface detachment. In contrast, the uptake of multibranched NSTs did not induce gross changes in macrophage shape or adhesion, but correlated instead with cell enlargement and signatures of macrophage activation such as TNF-α and ROS. MTT assays indicate a low cytotoxic response to either SCS-NPs or NSTs despite differences in macrophage behavior. These observations show that differences in NP size and shape are sufficient to produce diverse responses in macrophages following uptake.}, number={22}, journal={Nanoscale}, author={Xia, W. and Song, H. M. and Wei, Q. S. and Wei, A.}, year={2012}, pages={7143–7148} } @article{wei_wei_leonov_2011, title={Gold Nanorods as Theranostic Agents}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84879348945&partnerID=MN8TOARS}, DOI={10.1002/9780470767047.ch27}, abstractNote={This chapter contains sections titled: Introduction Physical Properties of GNRs Synthesis of GNRs Surface Chemistry of GNRs GNRs as Theranostic Agents Outlook Acknowledgments References}, journal={Nanoplatform-Based Molecular Imaging}, publisher={John Wiley & Sons, Inc.}, author={Wei, Alexander and Wei, Qingshan and Leonov, Alexei P.}, year={2011}, month={May}, pages={659–681} } @article{tang_wei_wei_2011, title={Metal-Mesh Lithography}, volume={3}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000298341300038&KeyUID=WOS:000298341300038}, DOI={10.1021/am201305x}, abstractNote={Metal-mesh lithography (MML) is a practical hybrid of microcontact printing and capillary force lithography that can be applied over millimeter-sized areas with a high level of uniformity. MML can be achieved by blotting various inks onto substrates through thin copper grids, relying on preferential wetting and capillary interactions between template and substrate for pattern replication. The resulting mesh patterns, which are inverted relative to those produced by stenciling or serigraphy, can be reproduced with low micrometer resolution. MML can be combined with other surface chemistry and lift-off methods to create functional microarrays for diverse applications, such as periodic islands of gold nanorods and patterned corrals for fibroblast cell cultures.}, number={12}, journal={Acs Applied Materials & Interfaces}, author={Tang, Z. and Wei, Q. S. and Wei, A.}, year={2011}, pages={4812–4818} } @article{wei_wei_2011, title={Optical Imaging with Dynamic Contrast Agents}, volume={17}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000287562300001&KeyUID=WOS:000287562300001}, DOI={10.1002/chem.201002521}, abstractNote={Abstract}, number={4}, journal={Chemistry-a European Journal}, author={Wei, Q. S. and Wei, A.}, year={2011}, pages={1080–1091} } @article{stensberg_wei_mclamore_porterfield_wei_sepulveda_2011, title={Toxicological studies on silver nanoparticles: challenges and opportunities in assessment, monitoring and imaging}, volume={6}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000293335200014&KeyUID=WOS:000293335200014}, DOI={10.2217/nnm.11.78}, abstractNote={ Silver nanoparticles (Ag NPs) are becoming increasingly prevalent in consumer products as antibacterial agents. The increased use of Ag NP-enhanced products may lead to an increase in toxic levels of environmental silver, but regulatory control over the use or disposal of such products is lagging due to insufficient assessment on the toxicology of Ag NPs and their rate of release into the environment. In this article we discuss recent research on the transport, activity and fate of Ag NPs at the cellular and organismic level, in conjunction with traditional and recently established methods of nanoparticle characterization. We include several proposed mechanisms of cytotoxicity based on such studies, as well as new opportunities for investigating the uptake and fate of Ag NPs in living systems. }, number={5}, journal={Nanomedicine}, author={Stensberg, M. C. and Wei, Q. S. and McLamore, E. S. and Porterfield, D. M. and Wei, A. and Sepulveda, M. S.}, year={2011}, pages={879–898} } @article{wei_wei_2010, title={Cellular Interactions of Plasmon-Resonant Gold Nanorods}, DOI={10.1002/9780470875780.ch26}, abstractNote={This chapter contains sections titled: Introduction Surface Chemistry of GNRs Biocompatibility and Cellular Uptake of GNRs Cellular Imaging with GNRs GNRs as Photothermal Agents Conclusion References}, journal={Organelle-Specific Pharmaceutical Nanotechnology}, publisher={John Wiley & Sons, Inc.}, author={Wei, Qingshan and Wei, Alexander}, year={2010}, month={Aug}, pages={507–533} } @article{wei_leonov_wei_2010, title={Gold nanorods: multifunctional agents for cancer imaging and therapy.}, volume={624}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77953375626&partnerID=MN8TOARS}, DOI={10.1007/978-1-60761-609-2_8}, abstractNote={Gold nanorods (GNRs) are strongly absorbing at near-infrared (NIR) frequencies and can be employed as multifunctional agents for biological imaging and theragnostics. GNRs can support nonlinear optical microscopies based on two-photon-excited luminescence and can enhance the contrast of biomedical imaging modalities such as optical coherence tomography and photoacoustic tomography. GNRs are also efficient at mediating the conversion of NIR light energy into heat and can generate localized photothermal effects. However, future clinical applications will require the rigorous removal of CTAB, a micellar surfactant used in GNR synthesis, and reliable methods of surface functionalization for cell-selective targeting and for minimizing nonspecific uptake into cells. This can be accomplished by using polystyrenesulfonate (PSS) as a sorbent for removing CTAB, and in situ dithiocarbamate formation for introducing chemisorptive ligands onto GNR surfaces.}, journal={Methods in molecular biology (Clifton, N.J.)}, author={Wei, A. and Leonov, A.P. and Wei, Q.}, year={2010}, pages={119–130} } @article{song_wei_ong_wei_2010, title={Plasmon-Resonant Nanoparticles and Nanostars with Magnetic Cores: Synthesis and Magnetomotive Imaging}, volume={4}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000282121000027&KeyUID=WOS:000282121000027}, DOI={10.1021/nn101202h}, abstractNote={Plasmon-resonant gold nanostars (NSTs) with magnetic cores were synthesized by a multistep sequence from superparamagnetic Fe3O4 nanoparticles (NPs) and evaluated as optical contrast agents under magnetomotive (MM) imaging conditions. Core-shell Fe3O4@Au NPs were prepared in nonpolar organic solvents with nanometer control over shell thickness and with good epitaxy to the Fe3O4 surface. Anisotropic growth was performed in micellar solutions of cetyltrimethylammonium bromide (CTAB) under mildly reducing conditions, resulting in NSTs with physical features similar to those produced from colloidal gold seeds. NSTs could be produced below 100 nm from tip to tip, but seed size had a significant impact on growth habit, with larger seed particles producing submicrometer-sized "morning stars". Both NSTs and aggregated core-shell NPs are responsive to in-plane magnetic field gradients and can provide enhanced near-infrared (NIR) contrast under MM conditions, but do so by different mechanisms. NSTs can modulate polarized NIR scattering with minimal translational motion, giving the appearance of a periodic but stationary "blinking", whereas core-shell NP aggregates require lateral displacement for signal modulation. The polarization-sensitive MM imaging modality offers the dual advantage of enhanced signal quality and reduced background signal and can be applied toward the detection of magnetomotive NSTs in heterogeneous biological samples, as illustrated by their detection inside of granular cells such as macrophages.}, number={9}, journal={Acs Nano}, author={Song, H. M. and Wei, Q. S. and Ong, Q. K. and Wei, A.}, year={2010}, pages={5163–5173} } @inbook{wei_wei_2010, title={Plasmon-Resonant gold nanorods as multifunctional agents for diagnostics, imaging and photothermal therapy}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84881684232&partnerID=MN8TOARS}, DOI={10.4032/9789814267588}, booktitle={Handbook of Materials for Nanomedicine}, author={Wei, Q. and Wei, A.}, year={2010}, pages={585–631} } @article{wei_wei_2010, title={Signal Generation with Gold Nanoparticles: Photophysical Properties for Sensor and Imaging Applications}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84887032943&partnerID=MN8TOARS}, DOI={10.1002/9780470552704.ch10}, abstractNote={This chapter contains sections titled: Introduction Surface Plasmons Absorption Properties of Gold Nanoparticles Scattering Properties of Gold Nanoparticles Surface-Enhanced Raman Scattering (SERS) Surface-Enhanced Fluorescence Photoluminescence Nonlinear Optical Properties Concluding Remarks References}, journal={The Supramolecular Chemistry of Organic-Inorganic Hybrid Materials}, publisher={John Wiley & Sons, Inc.}, author={Wei, Qingshan and Wei, Alexander}, year={2010}, month={Jun}, pages={319–349} } @article{zhou_shao_qiao_wei_tang_jian_2010, title={Zwitterionic phosphorylcholine as a better ligand for gold nanorods cell uptake and selective photothermal ablation of cancer cells}, volume={46}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000274580700028&KeyUID=WOS:000274580700028}, DOI={10.1039/b915125g}, abstractNote={The conjugation of zwitterionic phosphorylcholine onto gold nanorods leads to enhanced and selective uptake within cancer cells.}, number={9}, journal={Chemical Communications}, author={Zhou, W. B. and Shao, J. Y. and Qiao, J. and Wei, Q. S. and Tang, J. G. and Jian, J.}, year={2010}, pages={1479–1481} } @article{wei_song_leonov_ritchie_wei_2009, title={COLL 347-Polarization-sensitive NIR imaging modalities based on gold nanorods and nanostars}, volume={238}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000207861903202&KeyUID=WOS:000207861903202}, journal={Abstracts of Papers of the American Chemical Society}, author={Wei, Q. S. and Song, H. M. and Leonov, A. and Ritchie, K. and Wei, A.}, year={2009} } @article{tong_wei_wei_cheng_2009, title={Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects}, volume={85}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000262486800003&KeyUID=WOS:000262486800003}, DOI={10.1111/j.1751-1097.2008.00507.x}, abstractNote={Abstract}, number={1}, journal={Photochemistry and Photobiology}, author={Tong, L. and Wei, Q. S. and Wei, A. and Cheng, J. X.}, year={2009}, pages={21–32} } @article{wei_song_leonov_hale_oh_ong_ritchie_wei_2009, title={Gyromagnetic Imaging: Dynamic Optical Contrast Using Gold Nanostars with Magnetic Cores}, volume={131}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000268399800034&KeyUID=WOS:000268399800034}, DOI={10.1021/ja901562j}, abstractNote={Plasmon-resonant nanoparticles with optical scattering in the near-infrared (NIR) are valuable contrast agents for biophotonic imaging and may be detected at the single-particle limit against a dark background, but their contrast is often limited in environments with high noise. Here we consider gyromagnetic imaging as a dynamic mode of optical contrast, using gold nanostars with superparamagnetic cores. The nanostars exhibit polarization-sensitive NIR scattering and can produce a frequency-modulated signal in response to a rotating magnetic field gradient. This periodic "twinkling" can be converted into Fourier-domain images with a dramatic reduction in background. We demonstrate gyromagnetic imaging of nanostars inside of tumor cells, using broadband excitation: while their time-domain signals are obscured by incoherent scattering, their Fourier-domain signals can be clearly resolved in less than a second. The gyromagnetically active nanostars do not cause a loss in viability, and can even have a mild stimulatory effect on cell growth.}, number={28}, journal={Journal of the American Chemical Society}, author={Wei, Q. S. and Song, H. M. and Leonov, A. P. and Hale, J. A. and Oh, D. M. and Ong, Q. K. and Ritchie, K. and Wei, A.}, year={2009}, pages={9728–9734} } @article{wei_zhou_ji_shen_2009, title={Thermosensitive Nanocables Prepared by Surface-Initiated Atom Transfer Radical Polymerization}, volume={4}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000262506500012&KeyUID=WOS:000262506500012}, DOI={10.1007/s11671-008-9206-5}, abstractNote={Abstract}, number={1}, journal={Nanoscale Research Letters}, author={Wei, Q. S. and Zhou, W. B. and Ji, J. and Shen, J. C.}, year={2009}, pages={84–89} } @article{wei_song_ong_ritchie_wei_2008, title={COLL 66-Gold nanostars with magnetic cores as dynamic optical imaging agents}, volume={236}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000270256303742&KeyUID=WOS:000270256303742}, journal={Abstracts of Papers of the American Chemical Society}, author={Wei, Q. S. and Song, H. M. and Ong, Q. K. and Ritchie, K. and Wei, A.}, year={2008} } @inproceedings{wei_ji_shen_2008, title={NIR responsive core/shell nanohybrids for smart drug delivery}, volume={1}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84869034553&partnerID=MN8TOARS}, booktitle={8th World Biomaterials Congress 2008}, author={Wei, Q. and Ji, J. and Shen, J.}, year={2008}, pages={297} } @article{wei_ji_shen_2008, title={Synthesis of near-infrared responsive gold nanorod/PNIPAAm core/shell nanohybrids via surface initiated ATRP for smart drug delivery}, volume={29}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000255716800004&KeyUID=WOS:000255716800004}, DOI={10.1002/marc.200800009}, abstractNote={Abstract}, number={8}, journal={Macromolecular Rapid Communications}, author={Wei, Q. S. and Ji, J. and Shen, J. C.}, year={2008}, pages={645–650} } @article{wang_wei_wu_hu_ji_wang_2008, title={The Escherichia coli O157 : H7 DNA detection on a gold nanoparticle-enhanced piezoelectric biosensor}, volume={53}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000254999100010&KeyUID=WOS:000254999100010}, DOI={10.1007/s11434-007-0529-x}, abstractNote={This paper presents development of a quartz crystal microbalance (QCM) biosensor for real-time detection of E. coli O157:H7 DNA based on nanogold particles amplification. Many inner Au nanoparticles were immobilized onto the thioled surface of the Au electrode, then more specific thiolated single-stranded DNA (ssDNA) probes could be fixed through Au-SH bonding. The hybridization was induced by exposing the ssDNA probe to the complementary target DNA of E. coli O157:H7 gene eaeA, then resulted in a mass change and corresponding frequency shifts (Δf) of the QCM. The outer avidin-coated Au nanoparticles could combine with the target DNA to increase the mass. The electrochemical techniques, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were adopted to manifest and character each step. The target DNA corresponding to 2.0×103 colony forming unit (CFU)/mL E. coli O157:H7 cells can be detected by this biosensor, so it is practical to develop a sensitive and effective QCM biosensor for pathogenic bacteria detection based on specific DNA analysis. The piezoelectric biosensing system has potential for further applications, such as food safety and environment monitoring, and this approach lays the groundwork for incorporating the method into an integrated system for in-field bacteria detection.}, number={8}, journal={Chinese Science Bulletin}, author={Wang, L. J. and Wei, Q. S. and Wu, C. S. and Hu, Z. Y. and Ji, J. and Wang, P.}, year={2008}, pages={1175–1184} } @article{he_henne_wei_zhao_doorneweerd_cheng_low_wei_2008, title={Two-Photon Luminescence Imaging of Bacillus Spores Using Peptide-Functionalized Gold Nanorods}, volume={1}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000207467500002&KeyUID=WOS:000207467500002}, DOI={10.1007/s12274-008-8047-y}, abstractNote={Bacillus subtilis spores (a simulant of Bacillus anthracis) have been imaged by two-photon luminescence (TPL) microscopy, using gold nanorods (GNRs) functionalized with a cysteine-terminated homing peptide. Control experiments using a peptide with a scrambled amino acid sequence confirmed that the GNR targeting was highly selective for the spore surfaces. The high sensitivity of TPL combined with the high affinity of the peptide labels enables spores to be detected with high fidelity using GNRs at femtomolar concentrations. It was also determined that GNRs are capable of significant TPL output even when irradiated at near infrared (NIR) wavelengths far from their longitudinal plasmon resonance (LPR), permitting considerable flexibility in the choice of GNR aspect ratio or excitation wavelength for TPL imaging.}, number={6}, journal={Nano Research}, author={He, W. and Henne, W. A. and Wei, Q. S. and Zhao, Y. and Doorneweerd, D. D. and Cheng, J. X. and Low, P. S. and Wei, A.}, year={2008}, pages={450–456} } @article{wei_ji_shen_2008, title={pH Controlled Synthesis of High Aspect-Ratio Gold Nanorods}, volume={8}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000261390800015&KeyUID=WOS:000261390800015}, DOI={10.1166/jnn.2008.302}, abstractNote={Here we report the two-step synthesis of high aspect-ratio gold nanorods via combining low pH growth and higher cetyltrimethylammonium bromide concentration. The approach is motivated by the "slow growth principle", which has been demonstrated recently as a effective protocol to prepare high aspect-ratio one-dimensional nanostructures. When the pH value of the growth solution gradually decreased, the growth rate of nanorods was significantly decreased and a continuous morphological changing from uniform monodisperse gold nanospheres to extraordinary long gold nanorods occured. By simultaneously decreasing the growth pH and increasing the concentration of cetyltrimethylammonium bromide, the length of gold nanorods could be further elongated to above 2 microm with large aspect-ratio of above 80. This kind of high aspect-ratio gold nanorods could be excellent building blocks for optical or electrical nanodevices in future.}, number={11}, journal={Journal of Nanoscience and Nanotechnology}, author={Wei, Q. S. and Ji, J. and Shen, J. C.}, year={2008}, pages={5708–5714} } @inproceedings{wang_wei_wu_ji_wang_2007, title={A QCM biosensor based on gold nanoparticles amplification for real-time bacteria DNA detection}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-47349090524&partnerID=MN8TOARS}, DOI={10.1109/ICIA.2007.4295695}, abstractNote={A DNA piezoelectric biosensing method for real-time detection of E. coli O157:H7 in a circulating-flow system was developed in this study. The thioled surface of the Au electrode could be immobilized by many inner Au nanoparticles, then more thiolated single-stranded DNA (ssDNA) probes which was specific to E. coli O157:H7 eaeA gene could be fixed through Au-SH bonding. The hybridization was induced by exposing the ssDNA probe to the complementary target DNA, then resulted in the mass change and corresponding frequency shifts ( Af ) of the QCM. The outer avidin-coated Au nanoparticles could combine with the target DNA to increase the mass. The inner and outer Au nanoparticles with different diameters would play the "signal amplifier" role at different layer for improving the detection limit and sensitivity. The electrochemical techniques, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), are adopted to demonstrate and character each treatment. The target DNA corresponding to 2.0 X 103 colony forming unit (CFU)/ml E. coli 0157:H7 cells can be detected by this biosensor, so it is practical to develop a sensitive and effective QCM biosensor for pathogenic bacteria detection based on specific DNA analysis.}, booktitle={Proceedings of the 2007 International Conference on Information Acquisition, ICIA}, author={Wang, L. and Wei, Q. and Wu, C. and Ji, J. and Wang, P.}, year={2007}, pages={46–51} } @inproceedings{wang_wei_wu_ji_liu_yang_wang_2007, title={Detection of E. coli O157:H7 DNA by a novel QCM biosensor coupled with gold nanoparticles amplification}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-52949115337&partnerID=MN8TOARS}, DOI={10.1109/NANO.2007.4601201}, abstractNote={In recent years, quartz crystal microbalance (QCM) plays an important role in many biological detections, and the enhancement of a single strain DNA probe linked to the sensor surface is of crucial importance in DNA molecule recognition. By means of nanogold modification and mass amplification, a QCM biosensor for Escherichia coli O157:H7 DNA detection was explored and developed in this work. As a suitable surfactant, 1,6-Hexanedithiol was introduced onto the Au surface of QCM, then self-assembled to provide a thioled interface for the inner goldnano immobilization. Based on the Au-SH binding mechanism, thiolated single-stranded DNA (ssDNA) probes which was specific to E. coli O157:H7 eaeA gene would link to the nanoparticle-modified electrode surface. The hybridization was induced by exposing the ssDNA probe to the complementary target DNA, but the frequency change caused by the captured target DNA was negligible. In order to amplify the signal, outer nanogold as the mass enhancer were applied to combine with the target DNA by the biotin-avidin system. The electrochemical techniques, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), are adopted to manifest and character each step, which supplied some reasonable and powerful supports for the frication and detection of this QCM biosensor. The target DNA corresponding to 2.0 times 103 colony forming unit (CFU)/ml E. coli O157:H7 can be detected by this biosensor, so it is practical to develop a sensitive and effective QCM biosensor for pathogenic bacteria detection based on specific DNA analysis. In order to attract more attention, this DNA biosensor should be combined with some micro- and nano-fabrication techniques to realize more promising and pratical applications, and more attention should be focused on the further improvement of the sensitivity and the shorten of analysis time.}, booktitle={2007 7th IEEE International Conference on Nanotechnology - IEEE-NANO 2007, Proceedings}, author={Wang, L. and Wei, Q. and Wu, C. and Ji, A. and Liu, Q. and Yang, M. and Wang, P.}, year={2007}, pages={330–333} } @article{wei_ji_fu_shen_2007, title={Norvancomycin-capped silver nanoparticles: Synthesis and antibacterial activities against E-coli}, volume={50}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000247829200017&KeyUID=WOS:000247829200017}, DOI={10.1007/s11426-007-0028-6}, number={3}, journal={Science in China Series B-Chemistry}, author={Wei, Q. S. and Ji, J. and Fu, J. H. and Shen, J. C.}, year={2007}, pages={418–424} }