We propose and demonstrate low-refractive-index particles with all-dielectric metamaterial shell which lead to formation of high intensity photonic nanojets. We show that the extra degree of freedom because of the anisotropy of the shell gives rise to an increase in the photonic jet intensity inside the metamaterial shell without a need to increase the size of the particle. The anisotropy of the shell can also control the spectral and spatial location of the Mie-type multipolar resonances to achieve the desired scattering. In experiments, the metamaterial shell is composed of strong nonlinear materials leading to enhanced nonlinear wavelength conversion at nanoscale.
We have developed two terahertz (THz) polarimetric methodologies based on terahertz time-domain spectroscopy (THz- TDS) incorporating three wire-grid polarizers. They require no change to existing THz-TDS setups and are free of any complicated electronic controls and synchronizations. In addition to the standard quantities measured by THz-TDS such as transmission and optical constants, they provide complete information on the anisotropy and chirality for a generalized material through measurements of the full electric field vector and hence the Jones matrix, and calculating specific quantities. Thus terahertz time-domain polarimetry (THz-TDP) can be considered as an upgrade of the conventional THz- TDS, needed for full characterization of anisotropic and chiral materials. In this paper, we describe the details of the experimental settings, mathematical procedures and property quantifications in these methodologies. We present experimental results on an anisotropic polymer sheet showing the effectiveness of the methods, and preliminary data for chiral DNA molecules for the first time in the THz frequency range.
Many nanoparticle contrast agents have difficulties with deep tissue and near-bone imaging due to limited penetration of visible photons in the body and mineralized tissues. We are looking into the possibility of mediating this problem while retaining the capabilities of the high spatial resolution associated with optical imaging. As such, the potential combination of emerging photoacoustic imaging and nuclear imaging in monitoring of antirheumatic drug delivery by using a newly developed dual-modality contrast agent is investigated. The contrast agent is composed of gold nanorods (GNRs) conjugated to the tumor necrosis factor (TNF-α) antibody and is subsequently radiolabeled by 125I. ELISA experiments designed to test TNF-α binding are performed to prove the specificity and biological activity of the radiolabeled conjugated contrast agent. Photoacoustic and nuclear imaging are performed to visualize the distribution of GNRs in articular tissues of the rat tail joints in situ. Findings from the two imaging modalities correspond well with each other in all experiments. Our system can image GNRs down to a concentration of 10 pM in biological tissues and with a radioactive label of 5 μCi. This study demonstrates the potential of combining photoacoustic and nuclear imaging modalities through one targeted contrast agent for noninvasive monitoring of drug delivery as well as deep and mineralized tissue imaging.
We have investigated the potential of emerging photoacoustic imaging and nuclear imaging in monitoring of drug
delivery by using a newly developed dual-modality contrast agent. After the contrast agent composed of gold
nanorods (GNRs) was produced, it was radiolabeled by [125I] with high yield and without disturbing the optical
properties of the contrast agent. Photoacoustic and nuclear imaging were conducted to visualize the distribution of
GNRs in articular tissues of rat tail joints in situ. Findings from the two modalities corresponded well with each
other. Using the current imaging systems, GNRs down to a concentration of 10 pM in biological tissues and with a
radioactive label of 5 μCi can be imaged. Moreover, by radiolabeling the GNRs, the in vivo behaviors of the contrast
agent can be monitored conveniently using γ-camera, allowing validation of the findings from emerging
photoacoustic technique. Enabled by the high sensitivity of nuclear imaging, whole-body and longitudinal studies of
the biodistribution of GNRs contrast agent can be performed noninvasively and repeatedly in the same animal. The
highly efficient method reported here provides an extensively useful tool for the guidance of design and
development of new gold nanoparticles as target-specific agents for both diagnostics and therapy.
Multiple cardiovascular inflammatory biomarkers were simultaneously imaged in vivo using antibody conjugated
gold nanorods (GNRs) injected into a mouse model of vascular injury stimulated by a photochemical reaction of Rose
Bengal dye to green light. Mixed solutions of ICAM-1 antibody conjugated GNRs (715 nm) and E-selectin antibody
conjugated GNRs (800 nm) were injected to bind to their respective inflammatory markers on the luminal surface of the
inferior vena cava of a mouse. Photoacoustic intensity was measured by a commercial ultrasound probe synchronized to
a pulsed laser (10-18 mJ/cm2) at 715 nm or 800 nm clearly identified the upregulation of targeted biomarkers.
Histopathology on the harvested tissues confirmed inflammation. The feasibility of simultaneous photoacoustic
molecular imaging of inflammation responses in cardiovascular system using a commercial ultrasound system has been
demonstrated in vivo.
KEYWORDS: Skin, Corrosion, Electrodes, Nanocomposites, Sensors, Carbon, Structural health monitoring, Aluminum, Finite element methods, Chemical elements
The integrity and safety of metallic structures can be jeopardized by structural damage (e.g., yielding, cracking, impact, corrosion) that can occur during operation or service. While a variety of sensors have been proposed and validated for structural health monitoring, most sensors only provide data regarding a discrete point on the structure, thereby requiring densely-distributed sensors; however, such an approach may be infeasible for many structures due to geometrical and economic constraints. In this study, a nanoengineered carbon nanotube-polyelectrolyte sensing skin is proposed for monitoring strain, impact, and corrosion of metallic structures. Experimental validation studies have verified that these conformable films exhibit highly sensitive electromechanical and electrochemical responses to applied strain and corrosion processes, respectively. Here, the proposed nanocomposite is coupled with an electrical impedance tomographic (EIT) conductivity imaging technique. Unlike traditional point-based sensing transducers, EIT reconstructs two-dimensional skin conductivity distributions for damage identification of large structural components. Since EIT relies solely on boundary electrical measurements, one does not need to physically probe each structural location for data acquisition. Instead, any structural damage that affects the nanocomposite coating will produce localized changes in film conductivity detectable via EIT and boundary electrical measurements.
Cardiovascular inflammatory activity was imaged in vivo. Inflammation is known to be a major cause of
cardiovascular disease. Photoacoustic (PA) imaging was employed using bio-conjugated gold nanorods (GNR) as a
contrast agent. A mouse model based on vascular endothelium injury by a photochemical reaction of Rose Bengal (RB)
dye to green light laser was used. Following a mid-line laparotomy under an approved animal protocol, anti-ICAM-1
conjugated GNR was injected through the dorsal penile vein followed by RB injection through the same vein. The
inferior vena cava immediately distal to the renal veins of a C57BL/6 mouse was exposed to the green light laser for 10
minutes. The peak absorption of GNR was tuned to be 700 nm to minimize possible background absorption by blood
and RB. The stability of GNR in the blood plasma was tested in vitro. Photoacoustic images were obtained through an
ultrasound gel pouch in the mouse abdomen using a commercial ultrasound probe to evaluate inflammatory changes to
the vascular endothelium, confirmed by histology. Preliminary results demonstrate the feasibility of in vivo
photoacoustic imaging by a commercial ultrasound scanner of inflammation using GNR as a contrast agent.
Photoacoustic (PA) imaging provides excellent optical contrast with decent penetration and high spatial resolution, making it attractive for a variety of neural applications. We evaluated optical contrast agents with high absorption in the near infrared (NIR) as potential enhancers for PA neuroimaging: optical dyes, gold nanorods (GNRs) and PEBBLEs loaded with indocyanine green. Two PA systems were developed to test these agents in excised neural tissue and in vivo mouse brain. Lobster nerves were stained with the agents for 30 minutes and placed in a hybrid nerve chamber capable of electrical stimulation and recording, optical spectroscopy and PA imaging. Contrast agents boosted the PA signal by at least 30 dB using NIR
illumination from a tunable pulsed laser. Photobleaching may be a limiting factor for optical dyes-the PA signal decreased steadily with laser illumination. The second setup enabled in vivo transcranial imaging of the mouse brain. A custom clinical ultrasound scanner and a 10-MHz linear array provided near real-time
images during and after an injection of 2 nM gold nanorods into the tail vein. The peak PA signal from the brain vasculature was enhanced by up to 2 dB at 710 nm. Temporal dynamics of the PA signal were also consistent with mixing of the GNRs in the blood. These studies provide a baseline for enhanced PA imaging in neural tissue. The smart contrast agents employed in this study can be further engineered for molecular targeting and controlled drug delivery with potential treatment for a myriad of neural disorders.
This paper demonstrated the physical properties of a layer-by-layer (LBL) assembled single-walled carbon nanotubes
(SWNTs) - polymer composite thin film. The superior mechanical and electrical properties that originate from SWNTs
were successfully incorporated into a polymeric thin film by hydrogen bonding-directed LBL assemblies. The electrical
conductivities and mechanical strength of a LBL composite are 8.5*103 S/m and 160 MPa with only 8±2wt% SWNT
loading. The combination of high electrical and mechanical properties of SWNT-polymer LBL thin films makes this
material unique, opening the way for a wide range of applications from flexible electronics to space telescopes and
biomedical implantable devices.
The recent development of wireless sensors for structural health monitoring has revealed their strong dependency on
portable, limited battery supplies. Unlike current wireless sensors, passive radio frequency identification (RFID)
systems based on inductive coupling can wirelessly receive power from a portable reader while transmitting collected
data back. In this paper, preliminary results of a novel inductively coupled strain and corrosion sensor based upon
material fabrication techniques from the nanotechnology field are presented. By varying polyelectrolyte species during a
layer-by-layer fabrication process, carbon nanotube-polyelectrolyte multilayer thin film sensors sensitive to different
mechanical (e.g. strain) and chemical (e.g. pH) stimuli can be produced. Validation studies conducted with different
carbon nanotube thin films designed as either strain or pH sensors reveal high sensitivity and linear performance. When
coupled with a copper inductive coil antenna, resulting RFID-based sensors exhibit wirelessly readable changes in
resonant frequency and bandwidth. Furthermore, a carbon nanotube-gold nanocomposite thin film is fabricated and
patterned into a highly conductive coil structure to realize a novel thin film inductive antenna. Preliminary results
indicate that nanotube-gold nanocomposites exhibit resonance conditions, holding great promise for future RFID applications.
The development of gold nanoparticles for molecular optoacoustic imaging is a very promising area of research and development. Enhancement of optoacoustic imaging for molecular detection of tumors requires the engineering of nanoparticles with geometrical and molecular features that can enhance selective targeting of malignant cells while optimizing the sensitivity of optoacoustic detection.
In this article, cylindrical gold nanoparticles (i.e. gold nanorods) were fabricated with a plasmon resonance frequency in the near infra-red region of the spectrum, where deep irradiation of tissue is possible using an Alexandrite laser. Gold nanorods (Au-NRs) were functionalized by covalent attachment of Poly(ethylene glycol) to enhance their biocompatibility. These particles were further functionalized with the aim of targeting breast cancer cells using monoclonal antibodies that binds to Her2/neu receptors, which are over expressed on the surface of breast cancer cells. A custom Laser Optoacoustic Imaging System (LOIS) was designed and employed to image nanoparticle-targeted cancer cells in a phantom and PEGylated Au-NRs that were injected subcutaneously into a nude mouse. The results of our experiments show that functionalized Au-NRs with a plasmon resonance frequency at near infra-red region of the spectrum can be detected and imaged in vivo using laser optoacoustic imaging system.
We have studied the potential of gold nanorods to target cancer cells and provide contrast for photoacoustic
imaging. The elongated "rod" shape of these nanoparticles provides a mechanism to tune their plasmon peak absorption
wavelength. The absorption peak is shifted to longer wavelengths by increasing the aspect ratio of the rods. Particles 15
nm in diameter and 45 nm long were prepared using a seed mediated growth method. Their plasmon absorption peak
was designed to be at 800 nm for increased penetration depth into biological tissue. They were conjugated with a
specific antibody to target prostate cancer cells. We have applied photoacoustics to image a prostate cell culture targeted
by conjugated gold particles. Images confirm the efficiency of conjugated particle binding to the targeted cell
membranes. Photoacoustic detection of a single cell layer is demonstrated. To evaluate the applicability of the technique
to clinical prostate cancer detection, we have imaged phantom objects mimicking a real tissue with small (2 mm size)
inclusions of nanoparticle gel solution. Our photoacoustic imaging setup is based on a modified commercial ultrasonic
scanner which makes it attractive for fast implementation in cancer diagnosis in clinical application. In addition, the
setup allows for dual mode operation where a photoacoustic image is superimposed on a conventional B-mode
ultrasound image. Dual mode operation is demonstrated by imaging a mouse with gold nanorod gel solution implanted
in its hind limb.
To measure component-level structural responses due to external loading, strain sensors can provide detailed information pertaining to localized structural behavior. Although current metal foil strain sensors are capable of measuring strain deformations, they suffer from disadvantages including long-term performance issues when deployed in the field environment. This paper presents a novel carbon-nanotube polymer composite thin film that can be tailored for specific strain sensing properties. Beginning at the nano-scale, molecular manipulation of single-walled carbon nanotubes (SWNT) is performed to control chemical fabrication parameters as a means of establishing a relationship with macroscale bulk sensor properties. This novel strain sensor is fabricated using the Layer-by-Layer (LbL) self-assembly process. A rigorous experimental methodology is laid out to subject a variety of thin films to tensile-compressive cyclic loading. In particular, SWNT concentration, polyelectrolyte concentration, and film thickness are varied during the fabrication process to produce a variety of strain sensors. This study correlates fabrication parameters with bulk strain sensor properties; sensor properties including sensitivity (gauge factor), linearity, and hysteresis, are explored.
A contrast agent for optoacoustic imaging and laser therapy of early tumors is being developed based on gold
nanocolloids strongly absorbing visible and near-infrared light. The optoacoustic signals obtained from gold nanospheres
and gold nanorods solutions are studied. In the case of 100 nm nanospheres as an example, a sharp increase in the total
area under the curve of the optoacoustic signal is observed when the laser fluence is increased beyond a threshold value
of about 0.1 J/cm2. The change in the optoacoustic signal profile is attributed to the formation of water vapor bubbles
around heated nanoparticles, as evidenced via thermoacoustic microscopy experiments. It has been determined that,
surprisingly, gold nanoparticles fail to generate detectable nanobubbles upon irradiation at the laser fluence of ~2
mJ/cm2, which heats the nanoparticles up to 374°C, the critical temperature of water. Only when the estimated
temperature of the particle reaches about 10,000°C, a marked increase of the optoacoustic pressure amplitude and a
changed profile of the optoacoustic signals indicate nanobubble formation. A nanoparticle based contrast agent is the
most effective if it can be activate by laser pulses with low fluence attainable in the depth of tissue. With this goal in
mind, we develop targeting protocols that form clusters of gold nanocolloid in the target cells in order to lower the
bubble formation threshold below the level of optical fluence allowed for safe laser illumination of skin. Experiments
and modeling suggest that formation of clusters of nanocolloids may improve the sensitivity of optoacoustic imaging in
the detection of early stage tumors.
A variety of colloidal semiconductor quantum dots and related quantum-wire structures are characterized using absorption and photoluminescence measurements. The electronic properties of these structures are modeled and compared with experiment. The characterization and application of ensembles of colloidal quantum dots with molecular interconnects are considered. The chemically-directed assembly of ensembles of colloidal quantum dots with biomolecular interconnects is demonstrated with quantum dot densities in excess of 10+17 cm-3. Non-charge transfer processes for switching based on dipole-dipole interactions - Forester interactions - are examined for colloidal quantum dots linked with biomolecules. Charge transport in biomolecules is studied using indirect-bandgap colloidal nanocrystals linked with biomolecules.
Photoluminescence (PL) enhancements of CdTe nanoparticles (NPs) and nanowires (NWs) are observed with the bioconjugation of metal NPs using d-biotin and streptavidin in solution. In the presence of metallic nanoparticles, strong enhancement of excitonic light emission of nanoparticles is observed. The enhancement effect is explained in terms of plasmon-assisted absorption of incident light and plasmon-induced increase of nanoparticles dipole moments. This supermolecules and bioconjugates system can be useful to build further efficient photonic devices and biological sensors.
Optoacoustic Tomography (OAT) is a rapidly growing technology that enables noninvasive deep imaging of biological tissues based on their light absorption. In OAT, the interaction of a pulsed laser with tissue increases the temperature of the absorbing components in a confined volume of tissue. Rapid perturbation of the temperature (<1°C) deep within tissue produces weak acoustic waves that easily travel to the surface of the tissue with minor attenuation. Abnormal angiogenesis in a malignant tumor, that increases its blood content, makes a native contrast for optoacoustic imaging; however, the application of OAT for early detection of malignant tumors requires the enhancement of optoacoustic signals originated from tumor by using an exogenous contrast agent. Due to their strong absorption, we have used gold nanoparticles (NP) as a contrast agent. 40nm spherical gold nanoparticles were attached to monoclonal antibody to target cell surface of breast cancer cells. The targeted cancer cells were implanted at depth of 5-6cm within a gelatinous object that optically resembles human breast. Experimental sensitivity measurements along with theoretical analysis showed that our optoacoustic imaging system is capable of detecting a phantom breast tumor with the volume of 0.15ml, which is composed of 25 million NP-targeted cancer cells, at a depth of 5 centimeters in vitro.
The mass-strength ratio is of exceptional importance for space application. The critical parts of both shuttle vehicles and satellites depends on strength and toughness of the materials they are made of, while strict limitations on the weight of the different components are placed by the launch technology. Single wall carbon nanotubes (SWNT) present significant potential as the basic material for the space applications. Exceptional mechanical properties of single wall carbon nanotubes (SWNT) have prompted intensive studies of SWNT composites. These qualities can also be used in a variety of other technologies from automotive to military and medical. However, the present composites have shown only a moderate strength enhancement when compared to other hybrid materials. Although substantial advances have been made, mechanical characteristics of SWNT-doped polymers are noticeably below their highly anticipated potential. Pristine SWNTs are well known for poor solubilization, which leads to phase segregation of composites. Severe structural inhomogeneities result in the premature failure of the hybrid SWNT/polymer materials. The connectivity with and uniform distribution within the matrix are essential structural requirements for the strong SWNT composites. Here we show that a new processing approach based on sequential layering of chemically-modified nanotubes and polyelectrolytes can greatly diminish the phase segregation and render SWNT composite highly homogeneous. Combined with chemical cross-linking, this processing leads to drastically improved mechanical properties. Tensile strength of the composites is several times higher than that of SWNT composites made via mixing; it approaches values seen for hard ceramics. The universality of the layering approach applicable to a wide range of functional materials makes possible successful incorporation of SWNT into a variety of composites imparting them required mechanical properties. The thin film membranes that are obtained in the result of the layer-by-layer process can be used as an intermediate or as a component of ultrastrong laminates. At the same time, the prepared membranes can also be utilized in the as-prepared form for the large area space telescopes (both radio and optical) because the combine the strength and multiple functionality of the SWNT membranes with the ease of deployment.
Optoacoustic tomography (OAT) is a medical imaging method for detection of cancerous tumors that uses laser pulses to produce transi ultrasonic waves with spatial profiles replicating distribution of absorbed optical energy. Unlike conventional ultrasonography that uses an external source of acoustic waves, OAT uses transient acoustic waves generated as result of thermal expansion of tissue preferentially heated with short laser pulses. Tissues with different optical properties have different optoacoustic profiles and this enables reconstruction of an acoustic image based on distribution of optical absorption. It is anticipated that the difference in optical absorption between very early tumors and normal tissues might be minimal, justifying application of a contrast agent. Gold Nanoparticles (NP) can be designed to strongly absorb desirable color of laser pulses and effectively produce acoustic waves. Therefore, gold NP can be potentially employed as an optoacoustic contrast agent. We studied sensitivity of optoacoustic imaging in phantoms resembling dimensions and properties of the breast with small objects loaded with gold NPs of various concentrations. Targeted selective loading of breast cancer cells in culture with 40-nm diameter NPs was experimentally demonstrated with electron microscopy and fluorescence labeling techniques. To achieve selective targeting, Herceptin, a monoclonal antibody raised against Her2 receptor was conjugated to NPs using streptavidin-biotin conjugation as a linker. Targeting experiments simultaneously demonstrated that Mab/NPs conjugates inhibit cell proliferation of Her/neu positive cells. These data present the first step in development of a new technology for highly selective cancer chemotherapy with capability to diagnose the presence of malignant tumors and monitor the effects of the treatment.
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