Photoacoustic detection of circulating melanoma cells in the plasma layer of the blood [abstract]

Abstract only availableWhen a melanoma patient is diagnosed, aggressive treatment is advised in an effort to contain the disease. Although the initial malignant cells are destroyed, it is impossible to determine whether or not the cancer has metastasized until a secondary tumor forms. This can take months to discover, by which time the cancer could be advanced. Our research focuses on using photoacoustic signals to detect melanoma cells circulating in the blood, allowing for much earlier discovery and treatment of this type of cancer. Photoacoustic signals are produced when a laser illuminates a medium - blood, in this case - and the resultant pressure created by the light causes the medium to emit a sound wave. These waves are specific to the medium being illuminated, and melanoma cells can therefore be differentiated from surrounding blood cells based on the waveform it produces. Our current technique involves the in vitro separation of blood through centrifugation to isolate and test only the white blood cell layer since the contrast between these cells and melanoma cells is clear. Using this method, we have detected a single cancerous cell in the blood stream. However, the process could be made simpler if the plasma layer were used for detection instead of the white blood cell layer. This layer is easier to obtain after blood has been centrifuged, the optical difference between plasma cells and melanoma cells is more pronounced in this layer than in the white blood cell layer, and the possibility that any stray red blood cells could distort the results is eliminated. The primary focus has therefore been to determine whether or not melanoma cells are commonly found in the plasma layer of the blood. If such is the case, this research will be one step closer to revolutionizing the treatment of melanoma patients around the world.College of Engineering Undergraduate Research Optio

Determination of the efficacy of an applied vacuum at the skin surface during the laser therapy of Port Wine Stain (PWS) [abstract]

Abstract only availableWe will be doing experiments ex vivo using pig skin, which is very similar and much more attainable than human skin, to test the stress vs. strain relationship, elasticity (Young's Modulus) and research skin mechanics. Certain pathological conditions in skin, such as basal cell carcinoma, exhibit changes in skin mechanics. Thus, measuring skin elasticity may help in clinical identification of skin cancer borders. We will be using degraded pig skin and a tensile tester to create a model of skin strength. Skin will be degraded using collagenase to change the skin mechanical properties. After getting the results and data we will then compare this to skin deformation experiments using a vacuum cup which we can get from a simple and pain-free clinical study. By applying a low level vacuum to human skin, in vivo, we will measure the deformation of skin and extract the elasticity. Eventually, we would like to use this vacuum to help with laser light therapy to reduce the appearance of birthmarks made from blood-vessels (vacuum details and usage) as well as to diagnose other skin pathologies

Photoacoustic Detection of Circulating Prostate, Breast and Pancreatic Cancer cells using targeted Gold Nanoparticles: Implications of Green Nanotechnology in Molecular Imaging

Nanoscience Poster SessionCirculating tumor cells are hallmarks of metastasis cancer. The presence of circulating tumor cells in blood stream correlates with the severity of disease. Photoacoustic imaging (PA) of tumor cells is an attractive technique for potential applications in diagnostic imaging of circulating tumor cells. However, the sensitivity of photoacoustic imaging of tumor cells depends on their photon absorption characteristics. In this context, gold nanoparticle embedded tumor cells offer significant advantages for diagnostic PA of single cells. As the PA absorptivity is directly proportional to the number of nanoparticles embedded within tumor cells, the propensity of nanoparticles to internalize within tumor cells will dictate the sensitivity for single cell detection. We are developing biocompatible gold nanoparticles to use them as probes as part of our ongoing effort toward the application of X ray CT Imaging, Ultra Sound (US) and photoacoustic imaging of circulating breast, pancreatic and prostate tumor cells. We, herein report our latest results which have shown that epigallocatechin gallate (EGCG)-conjugated gold nanoparticles (EGCG-AuNPs) internalize selectively within cancer cells providing threshold concentrations required for photo acoustic signals. In this presentation, we will describe, our recent results on the synthesis and characterization of EGCG gold nanoparticles, their cellular internalization and photo acoustic imaging of PC-3 prostate cancer cells and PANC-1 pancreatic cancer cells

An Effective Strategy for the Synthesis of Biocompatible Gold Nanoparticles Using Cinnamon Phytochemicals for Phantom CT Imaging and Photoacoustic Detection of Cancerous Cells

This is a post-print version of the Pharmaceutical Research Article. The original publication is available at www.springerlink.com. DOI 10.1007/s11095-010-0276-6Purpose: The purpose of the present study was to explore the utilization of cinnamon coated gold nanoparticles (Cin-AuNPs) as CT/optical contrast enhancement agent for detection of cancer cells. Methods: Cin-AuNPs were synthesized by a “Green” procedure and the detailed characterization has been performed by physic-chemical analysis. Cytotoxicity and cellualar uptake studies were carried out in normal human fibroblast and cancerous (PC-3 and MCF-7) cells respectively. The efficacy of detecting cancerous cells was monitored using photoacoustic technique. In vivo biodistribution was studied after IV injection of Cin-AuNPs in mice and a CT phantom model was generated. Results: Biocompatible Cin-AuNPs were synthesized with high purity. Significant uptake of these gold nanoparticles was observed in PC-3 and MCF-7 cells. Cin-AuNPs internalized in cancerous cells facilitate detectable photoacoustic signals. In vivo biodistribution in normal mouse shows steady accumulation of gold nanoparticles in lungs and rapid clearance from blood. Quantitative analysis of CT values in phantom model reveals that the cinnamon phytochemicals coated AuNPs has reasonable attenuation efficiency. Conclusions: The results indicate that these non-toxic Cin-AuNPs can serve as excellent CT/ photoacoustic contrast enhancement agents and may provide a novel approach toward the tumor detection through nanopharmaceuticals.This work has been supported by grants from the National Institutes of Health/National Cancer Institute under the Cancer Nanotechnology Platform program (grant number: 5R01CA119412-01), NIH - 1R21CA128460-01; NIH-SBIR-Contract no. 241, and University of Missouri-Research Board - Program C8761 RB 06-030

Plasma Membrane Integrity and Survival of Melanoma Cells After Nanosecond Laser Pulses

Circulating tumor cells (CTCs) photoacoustic detection systems can aid clinical decision-making in the treatment of cancer. Interaction of melanin within melanoma cells with nanosecond laser pulses generates photoacoustic waves that make its detection possible. This study aims at: (1) determining melanoma cell survival after laser pulses of 6 ns at λ = 355 and 532 nm; (2) comparing the potential enhancement in the photoacoustic signal using λ = 355 nm in contrast with λ = 532 nm; (3) determining the critical laser fluence at which melanin begins to leak out from melanoma cells; and (4) developing a time-resolved imaging (TRI) system to study the intracellular interactions and their effect on the plasma membrane integrity. Monolayers of melanoma cells were grown on tissue culture-treated clusters and irradiated with up to 1.0 J/cm2. Surviving cells were stained with trypan blue and counted using a hemacytometer. The phosphate buffered saline absorbance was measured with a nanodrop spectrophotometer to detect melanin leakage from the melanoma cells post-laser irradiation. Photoacoustic signal magnitude was studied at both wavelengths using piezoelectric sensors. TRI with 6 ns resolution was used to image plasma membrane damage. Cell survival decreased proportionally with increasing laser fluence for both wavelengths, although the decrease is more pronounced for 355 nm radiation than for 532 nm. It was found that melanin leaks from cells equally for both wavelengths. No significant difference in photoacoustic signal was found between wavelengths. TRI showed clear damage to plasma membrane due to laser-induced bubble formation

An Analysis of the Abstracts Presented at the Annual Meetings of the Society for Neuroscience from 2001 to 2006

Annual meeting abstracts published by scientific societies often contain rich arrays of information that can be computationally mined and distilled to elucidate the state and dynamics of the subject field. We extracted and processed abstract data from the Society for Neuroscience (SFN) annual meeting abstracts during the period 2001–2006 in order to gain an objective view of contemporary neuroscience. An important first step in the process was the application of data cleaning and disambiguation methods to construct a unified database, since the data were too noisy to be of full utility in the raw form initially available. Using natural language processing, text mining, and other data analysis techniques, we then examined the demographics and structure of the scientific collaboration network, the dynamics of the field over time, major research trends, and the structure of the sources of research funding. Some interesting findings include a high geographical concentration of neuroscience research in the north eastern United States, a surprisingly large transient population (66% of the authors appear in only one out of the six studied years), the central role played by the study of neurodegenerative disorders in the neuroscience community, and an apparent growth of behavioral/systems neuroscience with a corresponding shrinkage of cellular/molecular neuroscience over the six year period. The results from this work will prove useful for scientists, policy makers, and funding agencies seeking to gain a complete and unbiased picture of the community structure and body of knowledge encapsulated by a specific scientific domain

Photoacoustic Detection of Metastatic Melanoma

Information used in this entry was gathered from http://tmir.missouri.edu/mte2011/Technology.html#lifesciencesWe in the Viator lab at the University of Missouri have invented a cell sorting apparatus that is capable of high throughput analysis of blood samples from patients at risk for metastatic melanoma. This invention is similar to flow cytometry except that we induce high frequency ultrasonic waves in pigmented melanoma cells as a result of nanosecond laser light absorption. We subsequently capture these cells for further study. We are adapting this technology for non-melanoma cancers by selective attachment of nanoparticles that act as targets for the laser. This technology serves as an early detector and monitor of metastatic disease. Currently, cancer metastasis is diagnosed by conventional imaging methods, such as CT, MRI, or PET scans. These imaging modalities require metastatic tumors to be several millimeters or more in order to show up on such scans. By this time, the metastatic tumors may be too advanced for effective therapy. Our technology detects metastatic disease when individual cells are traveling through the blood and lymph systems searching for distant organs in which to seed secondary tumors. Our laser induced ultrasonic flowmeter processes blood samples from patients, detecting metastatic disease at the single cell level. Thus, our low cost blood test can determine metastasis months or even years before current technology. Additionally, it only requires a simple blood draw from patients who have or are at risk for metastatic disease. The test is inexpensive and can be run in approximately one half hour. This method has been proven for melanoma detection and is being developed for other cancers. Potential Areas of Applications: High throughput screening for melanoma, Monitoring of melanoma patient, Isolation of melanoma cells. Patent Status: Issued Patent. Inventor(s): John A. Viator, Paul S. Dale, Devin McCormack, Kiran Bhattacharyya. This presentation was an elevator pitch at the Missouri Technology Expo 2011