Dr. Honggang Li Profile

Dr. Honggang Li

Research Assistant at Bio Tools Inc

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Publications (9)

Proceedings Article | 26 May 2011 Paper

Development of a depolarized Raman spectrometer for potential surface-enhanced Raman optical activity (SEROA) measurements

Honggang Li

Proceedings Volume 8025, 80250A (2011) https://doi.org/10.1117/12.883748

KEYWORDS: Raman spectroscopy, Spectroscopy, Raman scattering, Surface enhanced Raman spectroscopy, Polarization, Molecules, Light scattering, Optical activity, Molecular spectroscopy, Wave plates

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Raman optical activity (ROA) spectroscopy is a chiral sensitive vibrational spectroscopic technique that measures the difference of molecular responses to either left or right circularly polarized photon radiation. As a structural sensitive probe, ROA has great potential applications in fabricating bio-molecular sensors due to its capability of capturing small changes in molecular structure. However, ROA is a weak effect on the order of 10^-3 or 10^-4 smaller than its parent spontaneous Raman. Extension of ROA to widely sensing applications can be accelerated by combining it with surface plasmon resonance effect, surface-enhanced Raman spectroscopy (SERS), allowing for trace chemical detections. However, it has been shown to be very challenging to combine SERS with ROA to obtain a reliable surface-enhanced Raman optical activity measurement by several independent ROA research groups. This is because of the complexity of interaction of chiral molecules with metal surfaces. In addition, another main factor for the difficulty is the lack of a depolarized ROA spectrometer which can remove effectively huge polarized Raman bands, generally the major sources of artifacts in ROA. In this paper, we will discuss the development of a depolarized Raman spectrometer. This newly developed depolarized Raman instrument is based on the BioTools' ChiralRAMAN-2X scattered circular polarization (SCP) ROA spectrometer and has been modified into a dual circular polarization ROA spectrometer with the introducing circularity conversion in the incident radiation path. Combing the simultaneous detection of left and right circularly polarized scattering photons, newly developed Raman instrument are capable of modulate both incident and scattered light simultaneously resulting dual circular polarization (DCP) ROA measurements from depolarized parent Raman scattering. The performance of the Raman spectrometer has been initially evaluated with standard sample of small molecules for the proof-of-principle measurements of DCP-ROA, and its potential application in SEROA measurement has also been discussed.

Proceedings Article | 25 April 2009 Paper

Optimization of multilayer surface-enhanced Raman scattering (SERS) immuno-nanosensors via self-assembled monolayer spacers

Charles Klutse, Honggang Li, Brian Cullum

Proceedings Volume 7313, 73130C (2009) https://doi.org/10.1117/12.818124

KEYWORDS: Surface enhanced Raman spectroscopy, Metals, Self-assembled monolayers, Multilayers, Dielectrics, Molecules, Reflectivity, Raman scattering, Silica, Biological research

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Proceedings Article | 23 October 2006 Paper

Characterization of novel gold SERS substrates with multilayer enhancements

Honggang Li, Caitlin Baum, Brian Cullum

Proceedings Volume 6380, 63800D (2006) https://doi.org/10.1117/12.684688

KEYWORDS: Surface enhanced Raman spectroscopy, Silver, Gold, Multilayers, Oxides, Surface roughness, Metals, Optical spheres, Reflectivity, Silica

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Proceedings Article | 19 May 2006 Paper

Multilayer enhanced SERS active materials: fabrication, characterization, and application to trace chemical detection

Honggang Li, Caitlin Baum, Jian Sun, Brian Cullum

Proceedings Volume 6218, 621804 (2006) https://doi.org/10.1117/12.668935

KEYWORDS: Silver, Surface enhanced Raman spectroscopy, Silica, Multilayers, Metals, Dielectrics, Aluminum, Gold, Polymers, Oxides

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Proceedings Article | 11 November 2005 Paper

Label-free detection of antigens using implantable SERS nanosensors

Honggang Li, Caitlin Baum, Brian Cullum

Proceedings Volume 6007, 60070D (2005) https://doi.org/10.1117/12.629205

KEYWORDS: Surface enhanced Raman spectroscopy, Silver, Optical spheres, Nanosensors, Silica, Sensors, Proteins, Glasses, Raman scattering, Raman spectroscopy

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Proceedings Article | 12 May 2005 Paper

Implantable SERS nanosensors for pre-symptomatic detection of BW agents

Honggang Li, Jian Sun, Troy Alexander, Brian Cullum

Proceedings Volume 5795, (2005) https://doi.org/10.1117/12.607386

KEYWORDS: Surface enhanced Raman spectroscopy, Silver, Nanosensors, Silica, Proteins, Optical spheres, Raman scattering, Metals, Sensors, Raman spectroscopy

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The early detection of biological warfare (BW) agents before any symptoms are present is critical for saving lives and reducing cost of therapy. Protein expression in T-cells represents one of the earliest detectable cellular signaling events to occur in response to the exposure to various toxins or BW agents. In order to fully understand a cellular response to a particular BW agent, it is often necessary to monitor the expression of specific proteins. Therefore, we have developed a novel class of surface enhanced Raman scattering (SERS) immuno-nanosensors for the real-time monitoring of protein expression within individual living cells. In this work, we have developed and optimized novel nanosphere-based silver coated SERS nanosensors for the detection of proteins at cellular levels. SERS nanosensors were optimized in terms of nanosphere size, silver coating methods, number of silver layers, antibody binding and affinity. These nanosensors are capable of being inserted into individual cells and non-invasively positioned to the sub-cellular location of interest using optical tweezers. They were constructed from monodisperse silica nanospheres. These nanospheres were condensed from tetraalkoxysilanes in an alcoholic solution of water and ammonia. Accurate control of the silica nanospheres’ diameter was achieved by varying the reaction conditions. Nanosphere-based SERS immuno-nanosensors were then prepared by depositing multiple layers of silver on silica spheres, followed by binding of the antibody of interest to the silver. In binding the antibodies, different cross linker agents were characterized and compared. On one end, each of these cross linker agents contained sulfur or isothiocyanate groups which bound to the silver surface, while the other end contained a carboxylic or primary amine group which reacted readily with the antibodies. In order to improve sensitivity of these nanosensors, optimal silver surface coverage with crosslinkers was determined. Following binding of antibodies, evaluation of the nanosensors was performed by monitoring the SERS spectra of the nanosensors prior to and following exposure to the antigen of interest. These results showed reproducible differences in the SERS spectra upon exposure to the antigens confirming their ability to monitor trace amounts of antigen. In particular, these SERS-based nanosensors were shown successfully detect human insulin at trace levels.

Proceedings Article | 7 December 2004 Paper

Nanosphere-based SERS immuno-sensors for protein analysis

Honggang Li, Jian Sun, Brian Cullum

Proceedings Volume 5588, (2004) https://doi.org/10.1117/12.568038

KEYWORDS: Surface enhanced Raman spectroscopy, Silver, Silica, Optical spheres, Proteins, Raman spectroscopy, Raman scattering, Luminescence, Spectroscopy, Molecules

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We have developed and optimized novel nanosphere-based silver coated SERS substrates for the detection of proteins. These SERS substrates were optimized for silver thickness, number of silver layers, and extent of silver oxidation between layers. Immuno-nanosensors capable of being inserted into individual cells and non-invasively positioned to the sub-cellular location of interest using optical tweezers were constructed from monodisperse silica nanospheres. Silica nanospheres ranging in diameter from 100 to 4500 nm were condensed from tetraalkoxysilanes in an alcoholic solution of water and ammonia. By varying the reaction conditions, accurate control of the silica nanospheres’ diameter was achieved. Silica sphere sizes were optimized for SERS signal response. Nanosphere-based SERS substrates were made by depositing multiple layers of silver on the nanospheres, followed by binding of the antibody of interest to the silver. In binding the antibodies, different crosslinkers were characterized and compared. On one end, each of these crosslinkers contained sulfur or isothiocyanate groups which bound to the silver surface, while the other end contained a carboxylic or primary amine group which reacted readily with the antibodies. In order to evaluate these substrates, SERS spectra of different proteins, such as insulin and interleukin-2 (IL-2), were obtained. By using silver, as the metal surface for SERS, red and near-infrared excitation wavelengths (i.e., 600-700 nm) can be used. Excitation in this range helps to avoid photodamage to cells and reduces any autofluorescence background. Evaluation of these SERS substrates was performed using a 10 mW HeNe laser, operating at 632.8 nm, in a collinear excitation/detection geometry. The SERS signals were filtered with a holographic notch filter, dispersed by 1/3 meter spectrometer and detected using an intensified charge coupled device (ICCD). This paper discusses the fabrication and optimization of these nanosensors, as well as their potential applications.

Proceedings Article | 7 December 2004 Paper

Novel multilayered SERS substrates for trace chemical and biochemical analysis

Honggang Li, Pranav Patel, Brian Cullum

Proceedings Volume 5588, (2004) https://doi.org/10.1117/12.568039

KEYWORDS: Surface enhanced Raman spectroscopy, Silver, Coating, Optical spheres, Silica, Metals, Gold, Multilayers, Polymethylmethacrylate, Chemical analysis

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Proceedings Article | 15 March 2004 Paper

Development and optimization of SERS-based immuno-nanosensor for single cell analyses

Honggang Li, Brian Cullum

Proceedings Volume 5261, (2004) https://doi.org/10.1117/12.514702

KEYWORDS: Silver, Surface enhanced Raman spectroscopy, Multilayers, Coating, Sensors, Silica, Oxides, Raman scattering, Raman spectroscopy, Spectroscopy

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Surface enhanced Raman scattering (SERS) is an extremely sensitive and selective spectroscopic technique commonly employed for trace environmental analyses. We are currently developing and optimizing novel SERS based immuno-nanosensors for the monitoring of protein expression within individual living cells. These sensors, based upon antibody bound, silver coated silica nanospheres, can be inserted into individual cells and non-invasively positioned to the subcellular location of interest using optical tweezers. Because a HeNe laser is used for excitation, both photodamage to cells and cellular autofluorescence are minimized. Fabrication of the nanosensors is performed by first depositing a thin layer of silver on silica nanospheres by either homogeneous chemical deposition or vapor deposition. This is followed by binding an antibody against the analyte of interest to the sensor’s surface. In this paper we have investigated and optimized the reduction conditions of a chemical deposition substrate fabrication method and have compared these substrates to three types of vapor deposited substrates: (1) single layer silver film over nanosphere (SFON), (2) dual layer silver film over nanosphere (DUAL-FON) substrates (produced by coating an additional layer of silver film over the SFON), and (3) multilayer silver film over nanosphere (MULTI-FON) substrates (prepared by repeated coatings of several silver films over a SFON). In the case of chemical deposition, parameters optimized included silver nitrate concentration, reaction temperature, and silver coating time of substrates. In general, we have found SFON substrates yield better signal-to-noise ratios (S/N) with less background than the optimized, chemically prepared substrates. Even greater SERS enhancements have been found using multilayered SERS substrates (i.e., DUAL-FON substrates and MULTI-FON substrates). Both the stability and S/N of these substrates are enhanced by using multiple silver layers compared to SFON substrates of similar thickness. From this work, SERS signal enhancements of over an order of magnitude can be predicted by combining the enhancements obtained from the multilayered geometry and that from optimized silver deposition parameters. This paper includes investigations into the mechanism of multi-layer enhancement by studying the SERS S/N changes after different amount of exposure time of underlayer silver films to air. From these studies, we suggest that silver oxide layers play an important role in this multilayered enhancement. To the best of our knowledge, this paper is the first report of this type of silver oxide layer production affecting and even enhancing the resulting SERS signals from continuous film SERS substrates. In this paper, the fabrication, characterization and comparison of these SERS substrates in terms of enhancement factor, and lifetime will be discussed.

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