25. P. Diagaradjane, M. A. Yaseen, J. Yu, M. S. Wong, and B. Anvari, "Autofluorescence Characterization for the Early Diagnosis of Neoplastic Changes in DMBA/TPA Induced Mouse Skin Carcinogenesis", Lasers Surg. Med. 37, 382-395 (2005). DOI: 10.1002/lsm.20248
Background and Objective: Squamous cell carcinoma (SCC), the second most common skin cancer, usually remains confined to the epidermis for some time but eventually penetrates the underlying tissues, if left untreated. The non-invasive early detection of the SCC is important for appropriate therapeutic strategies. In this study, we aim to characterize the tissue transformation in DMBA/TPA induced mouse skin tumor model using autofluorescence excitation emission matrix (EEM) in conjunction with a multivariate statistical method for early detection of the neoplastic changes.
Study Design/Materials and Methods: The fluorescence EEM from experimental group (n = 40; DMBA/TPA application), control group (n = 6; acetone application), and the blank group (n = 6; no application of DMBA/TPA or acetone) were measured every week using a spectrofluorometer coupled with a fiber optic bundle. The EEM was recorded at excitation wavelengths from 280 to 460 nm at 10 nm intervals and the fluorescence emission was scanned from 300 to 750 nm. The fluorescence emission characteristics corresponding to different fluorophores were extracted from the EEM and the spectral data were used in a multiple/linear discriminant statistical algorithm.
Results: The changes in the fluorescence emission intensity were observed as early as the 1st week of tumor initiation by DMBA. Morphological changes as well as differences in the gross appearance of the skin surface were observed during the entire tumor initiation and promotion period of 15 weeks. The statistical analysis was performed for each excitation wavelength in the EEM and better classification accuracy was obtained for 280 and 410 nm excitations, corresponding to tryptophan and endogenous porphyrins, respectively. The statistical analysis of the combination wavelengths resulted in 11.6% increase in the overall classification accuracy when compared to the highest classification accuracy obtained with single wavelength analysis.
Conclusion: The intensity ratio mapping using the combination of emission intensities of key fluorophores such as tryptophan, collagen, NADH, and endogenous porphyrins from the measured EEM in conjunction with a simple multivariate statistical analysis can be used as a potential tool for the discrimination of early neoplastic changes with improved classification accuracy. Tryptophan and endogenous porphyrins may be used as biomarkers for the discrimination of early neoplastic changes when single wavelength excitations are used.
24. S. Asokan, K. M. Krueger, A. Alkhawaldeh, A. R. Carreon, Z. Mu, V. L. Colvin, N. V. Mantzaris and M. S. Wong, "The Use of Heat Transfer Fluids in the Synthesis of High-quality CdSe Quantum Dots, Core/Shell Quantum Dots, and Quantum Rods" Nanotechnology 16, 2000-2011 (2005). DOI: 10.1088/0957-4484/16/10/004
Fluorescent semiconductor nanoparticles, or quantum dots, have potential uses as an optical material, in which the optoelectronic properties can be tuned precisely by particle size. Advances in chemical synthesis have led to improvements in size and shape control, cost, and safety. A limiting step in large-scale production is identified to be the raw materials cost, in which a common synthesis solvent, octadecene, accounts for most of the materials cost for a batch of CdSe quantum dots. Thus, less expensive solvents are needed. In this paper, we identify heat transfer fluids, a class of organic liquids commonly used in chemical process industries to transport heat between unit operations, as alternative solvents for quantum dot synthesis. We specifically show that two heat transfer fluids can be used successfully in the synthesis of CdSe quantum dots with uniform particle sizes. We show that the synthesis chemistry for CdSe/CdS core/shell quantum dots and CdSe quantum rods can also be performed in heat transfer fluids. With the aid of a population balance model, we interpret the effect of different HT fluids on QD growth kinetics in terms of solvent effects, i.e., solvent viscosity, CdSe bulk solubility in the solvent, and surface free energy.
23. M. S. Wong and G. U. Lee, "Selected papers from the Fourth Topical Conference on Nanoscale Science and Engineering of the American Institute of Chemical Engineers" Nanotechnology 16, Preface (2005). DOI: 10.1088/0957-4484/16/7/E01
22. S. Laus, B. Sitharaman, É. Tóth, R. D. Bolskar, L. Helm, S. Asokan, M. S. Wong, L. J. Wilson and A. E. Merbach, "Destroying Gadofullerene Aggregates by Salt Addition in Aqueous Solution of Gd@C60(OH)x and Gd@C60[C(COOH2)]10" J. Am. Chem. Soc. 127, 9368 - 9369 (2005). DOI:10.1021/ja052388+
A combined proton relaxivity and dynamic light scattering study has shown that aggregates formed in aqueous solution of water-soluble gadofullerenes can be disrupted by addition of salts. The salt content of fullerene-based materials will strongly influence properties related to aggregation phenomena, therefore, their behavior in biological or medical applications. In particular, the relaxivity of gadofullerenes decreases dramatically with phosphate addition. Moreover, real biological fluids present a rather high salt concentration which will have consequences on fullerene aggregation and influence fullerene-based drug delivery.
21. R. K. Rana, V. S. Murthy, J. Yu and M. S. Wong, "Nanoparticle Self-assembly of Hierarchically Ordered Microcapsule Structures" Adv. Mater. 17, 1145-1150 (2005). (Cover Article) DOI: 10.1002/adma.200401612
Microcapsules with multilayer-thick shells are synthesized by depositing negatively charged nanoparticles around cationic polyamine aggregates crosslinked by multivalent counteranions (see Figure and inside cover). Nanoparticle (NP)-assembled microcapsules represent a new class of hollow-sphere material, in which materials properties can be programmed by way of NP and polymer compositions. Synthesis is based on a sequential self-assembly of NPs and polymer macromolecules. Reported by Wong and co-workers on p. 1145, this rapid, green synthesis technique applies to a wide spectrum of colloidal species and permits non-destructive encapsulation of water-soluble compounds. The inside cover shows a confocal microscopy image of water-filled microcapsules composed of silica NPs and a fluorescence-labelled polymer. The scale bar is 20 m. The inset shows a simplified illustration of the microcapsule assembly process.
20. S. Asokan, A. R. Carreon, Z. Mu, K. M. Krueger, A. Alkhawaldeh, V. L. Colvin and M.S. Wong,"Synthesis of High-Quality CdSe Nanocrystals in Heat Transfer Fluids" Proceed. of SPIE, Vol. 5705, Photonics West 2005, 60-67 (2005). DOI: 10.1117/12.597272
Fluorescent semiconductor nanoparticles, or quantum dots, have potential uses as an optical material, in which the optoelectronic properties can be tuned precisely by particle size. Advances in chemical synthesis have led to improvements in size and shape control, cost, and safety. A limiting step in large-scale production is identified to be the raw materials cost, in which a common synthesis solvent, octadecene, accounts for most of the materials cost in a batch of CdSe quantum dots. Thus, less expensive solvents are needed. In this paper, we identify heat transfer fluids, a class of organic liquids commonly used in chemical process industries to transport heat between unit operations, as alternative solvents for quantum dot synthesis. We specifically show that two heat transfer fluids can be used successfully in the synthesis of CdSe quantum dots with uniform particle sizes. We observe differences in particle growth using the various solvents.
19. P. Diagaradjane, M. A. Yaseen, J. Yu, M.S. Wong and B. Anvari, "Autofluorescence Characterization of DMBA/TPA Induced Two-Stage Carcinogenesis in Mouse Skin for the Early Detection of Tissue Transformation", Proceed. of SPIE, Vol. 5686, Photonics West 2005, 41-50 (2005). DOI: 10.1117/12.589328
The use of autofluorescence technique in the characterization of the sequential tissue transformation process in 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate (DMBA-TPA) induced two-stage mouse skin carcinogenesis model in conjunction with a suitable statistical method is being explored. The fluorescence excitation emission matrix (EEM) from experimental group (n=40; DMBA/TPA application), control group (n=6; acetone application) and the blank group (n=6; no application of DMBA/TPA or acetone) were measured every week using Fluoromax3 spectrofluorometer coupled with a waveguide fiber optic bundle (JY Horiba, NJ). The EEM was recorded for 19 excitation wavelengths from 280 to 460 nm at 10 nm intervals and the fluorescence emission was scanned from 300 to 750 nm. During the tissue transformation the epithelial tissues underwent biochemical and structural changes that are manifested in the tissue fluorescence. To correlate the tissue morphology with the observed fluorescence differences in the fluorescence emission, animals were sacrificed and the tissue biopsies were subjected to histopathological evaluation. The fluorescence emission corresponding to different fluorophores was extracted from the EEM, and the spectral data were used in multivariate statistical algorithm for the earliest diagnosis of the onset of tissue transformation. The intrinsic fluorescence from tryptophan, NADH and prophyrins showed distinct differences in the spectral signature during the tissue transformation, due to the altered metabolic activities of the cells. The statistical analysis of the spectral data corresponding to each excitation wavelength showed better classification accuracy at 280, 320, 350 and 405 nm excitations, corresponding to tryptophan, collagen, NADH and porphyrins with the classification accuracy of 74.3, 68.1, 64.6 and 74.7%, respectively. The variations in the spectral signature and the results of the statistical analysis suggest that porphyrins, tryptophan and NADH can be targeted as potential tumor markers in the early detection of the tissue transformation process.
18. M. A. Yaseen, P. Diagaradjane, B. M. Pikkula, J. Yu, M. S. Wong and B. Anvari, "Photothermal and Photochemical Effects of Laser Light Absorption by Indocyanine Green (ICG)" Proceed. of SPIE, Vol. 5695, Photonics West 2005, 27-35 (2005). DOI: 10.1117/12.589702
Indocyanine Green (ICG) is clinically used as a fluorescent dye for imaging purposes. Its rapid circulation kinetics and minimal toxicity has prompted investigation into ICG's utility as a photosentitizer for therapeutic applications. Traditionally, optically mediated tumor therapy has focused on photodynamic therapy, which employs a photochemical mechanism resulting from the absorption of low intensity CW laser light by localized photosensitizers such as Photofrin II, Benzoporphyrin Derivative (BPD), ICG. Treatment of cutaneous vascular malformations such as port-wine stains, on the other hand, is based on a photothermal mechanism resulting from the absorption of high intensity pulsed laser light by hemoglobin. In this study, we compared the effectiveness of combining photochemical and photothermal mechanisms during application of ICG in conjunction with laser irradiation with the intention that the combined approach may lead to a reduction in the threshold dose of pulsed laser light required to treat hypervascular malformations. The blood vessels in rabbit ears were used as an in vivo model for targeted vasculature. Irradiation of the ears with IR light (=785 nm, = 3 min, Io = 120 mW) was used to elicit photochemical damage, while photothermal damage was brought about using pulses from a ruby laser (=694 nm, = 3 ms) with different fluences. For the combined modality, photochemical damage was induced first and followed by photothermal irradiation. This modality was compared with photothermal irradiation alone. The effectiveness of each irradiation scheme was assessed using histopathological analysis. We present preliminary data that suggests that pretreatment with photodynamic therapy before photothermal coagulation results in more severe vascular damage with lower photothermal fluence levels. The results of this study provide the foundation work for further exploration of the therapeutic potentials of photochemical and photothermal effects during application of ICG in conjunction with laser irradiation.
17. M. O. Nutt, J. B. Hughes and M. S. Wong, "Designing Pd-on-Au Bimetallic Nanoparticle Catalysts for Trichloroethene Hydrodechlorination" Environ. Sci. Technol. 39, 1346 - 1353 (2005). DOI: 10.1021/es048560b