Dr. Rajan K. Bista Profile

Dr. Rajan K. Bista

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Publications (12)

SPIE Journal Paper | 4 June 2012 Open Access

Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

Rajan Bista, Shikhar Uttam, Douglas Hartman, Wei Qiu, Jian Yu, Lin Zhang, Randall Brand, Yang Liu

JBO, Vol. 17, Issue 06, 066014, (June 2012) https://doi.org/10.1117/12.10.1117/1.JBO.17.6.066014

KEYWORDS: Cancer, Tumors, Intestine, Mouse models, Statistical analysis, Oncology, Animal model studies, Microscopy, Tissues, Medicine

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The development of accurate and clinically applicable tools to assess cancer risk is essential to define candidates to undergo screening for early-stage cancers at a curable stage or provide a novel method to monitor chemoprevention treatments. With the use of our recently developed optical technology—spatial-domain low-coherence quantitative phase microscopy (SL-QPM), we have derived a novel optical biomarker characterized by structure-derived optical path length (OPL) properties from the cell nucleus on the standard histology and cytology specimens, which quantifies the nano-structural alterations within the cell nucleus at the nanoscale sensitivity, referred to as nano-morphology marker. The aim of this study is to evaluate the feasibility of the nuclear nano-morphology marker from histologically normal cells, extracted directly from the standard histology specimens, to detect early-stage carcinogenesis, assess cancer risk, and monitor the effect of chemopreventive treatment. We used a well-established mouse model of spontaneous carcinogenesis—ApcMin mice, which develop multiple intestinal adenomas (Min) due to a germline mutation in the adenomatous polyposis coli (Apc) gene. We found that the nuclear nano-morphology marker quantified by OPL detects the development of carcinogenesis from histologically normal intestinal epithelial cells, even at an early pre-adenomatous stage (six weeks). It also exhibits a good temporal correlation with the small intestine that parallels the development of carcinogenesis and cancer risk. To further assess its ability to monitor the efficacy of chemopreventive agents, we used an established chemopreventive agent, sulindac. The nuclear nano-morphology marker is reversed toward normal after a prolonged treatment. Therefore, our proof-of-concept study establishes the feasibility of the SL-QPM derived nuclear nano-morphology marker OPL as a promising, simple and clinically applicable biomarker for cancer risk assessment and evaluation of chemopreventive treatment.

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SPIE Journal Paper | 1 November 2011 Open Access

Correction of stain variations in nuclear refractive index of clinical histology specimens

Shikhar Uttam, Rajan Bista, Yang Liu, Douglas Hartman, Randall Brand

JBO, Vol. 16, Issue 11, 116013, (November 2011) https://doi.org/10.1117/12.10.1117/1.3650306

KEYWORDS: Refractive index, Tissues, Absorption, Pathology, Cancer, Animal model studies, Breast, Statistical modeling, Microscopy, Intestine

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SPIE Journal Paper | 1 July 2011 Open Access

Quantification of nanoscale nuclear refractive index changes during the cell cycle

Rajan Bista, Shikhar Uttam, Pin Wang, Kevin Staton, Randall Brand, Yang Liu, Serah Choi, Christopher Bakkenist, Douglas Hartman

JBO, Vol. 16, Issue 07, 070503, (July 2011) https://doi.org/10.1117/12.10.1117/1.3597723

KEYWORDS: Refractive index, Cancer, Microscopy, Flow cytometry, Medicine, Confocal microscopy, Diagnostics, Luminescence, Statistical analysis, Scattering

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Proceedings Article | 12 February 2011 Paper

Vibrational spectroscopic methods to characterize the bionanoparticles originating from newly developed self-forming synthetic PEGylated lipids (QuSomes)

Rajan Bista, Reinhard Bruch, Aaron Covington

Proceedings Volume 7908, 790808 (2011) https://doi.org/10.1117/12.875853

KEYWORDS: Raman spectroscopy, Spectroscopy, Infrared spectroscopy, Infrared radiation, Copper, FT-IR spectroscopy, Liquids, Temperature metrology, Thermography, Absorption

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Proceedings Article | 12 February 2011 Paper

Nanoscale nuclear architecture for cancer diagnosis by spatial-domain low-coherence quantitative phase microscopy

Pin Wang, Rajan Bista, Walid Khalbuss, Wei Qiu, Kevin Staton, Lin Zhang, Teresa Brentnall, Randall Brand, Yang Liu

Proceedings Volume 7907, 790704 (2011) https://doi.org/10.1117/12.874693

KEYWORDS: Cancer, Colorectal cancer, Cell biology, Microscopy, Diagnostics, Tumors, Animal model studies, Statistical analysis, Tissues, Signal detection

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Proceedings Article | 12 February 2011 Paper

Spatial-domain low-coherence quantitative phase microscopy for cancer diagnosis

Pin Wang, Rajan Bista, Rohit Bhargava, Randall Brand, Yang Liu

Proceedings Volume 7889, 78891Q (2011) https://doi.org/10.1117/12.873620

KEYWORDS: Cancer, Refractive index, Microscopy, Tissues, Scattering, Light sources, Signal detection, Light scattering, Breast cancer, Phase measurement

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SPIE Journal Paper | 1 November 2010 Open Access

Nanoscale nuclear architecture for cancer diagnosis beyond pathology via spatial-domain low-coherence quantitative phase microscopy

Pin Wang, Rajan Bista, Walid Khalbuss, Wei Qiu, Shikhar Uttam, Kevin Staton, Lin Zhang, Teresa Brentnall, Randall Brand, Yang Liu

JBO, Vol. 15, Issue 06, 066028, (November 2010) https://doi.org/10.1117/12.10.1117/1.3523618

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Proceedings Article | 16 February 2009 Paper

Near-infrared spectroscopic studies of self-forming lipids and nanovesicles

Rajan Bista, Reinhard Bruch

Proceedings Volume 7188, 718809 (2009) https://doi.org/10.1117/12.807406

KEYWORDS: Spectroscopy, Near infrared, Absorbance, Near infrared spectroscopy, Chemical analysis, Absorption, Micromirrors, Mirrors, Analytical research, Liquids

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Proceedings Article | 16 February 2009 Paper

Thin-layer infrared spectroscopic study on thermal behavior of non-phospholipid lipids and nanovesicles

Rajan Bista, Reinhard Bruch, Aaron Covington

Proceedings Volume 7188, 718808 (2009) https://doi.org/10.1117/12.806659

KEYWORDS: Liquids, Infrared spectroscopy, Spectroscopy, FT-IR spectroscopy, Infrared radiation, Thermography, Temperature metrology, Head, Chemical analysis, Copper

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Proceedings Article | 12 August 2008 Paper

First experimental study of self-forming synthetic lipids by confocal laser tweezers Raman spectroscopy

Rajan Bista, Reinhard Bruch

Proceedings Volume 7099, 709903 (2008) https://doi.org/10.1117/12.804822

KEYWORDS: Raman spectroscopy, Particles, Optical tweezers, Spectroscopy, Microscopes, Confocal microscopy, Objectives, Biomedical optics, Head, Liquids

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We present the first experimental study of self-forming synthetic lipids, trademarked as QuSomes^TM, using Raman spectroscopy in the spectral range of 500 to 3100 cm^-1. Raman spectra of these new artificial lipids composed of 1,2- dimyristoyl-rac-glycerol-3-dodecaethylene glycol (GDM-12) and 1,2-dioleoyl-rac-glycerol-3-dodecaethylene glycol (GDO-12) have been obtained in pure form and in aqueous suspensions with Phosphate Buffered Saline (PBS) by using an inverted confocal laser-tweezers-Raman-microscopy system. This spectrometer works with an 80 mW diode-pumped solid-state laser, operating at a wavelength of 785 nm in the TEM₀₀ mode. The laser is used both for optical trapping and Raman excitation. The two amphiphiles considered in this study, differ in their hydrophobic chain length and contain similar units of hydrophilic polyethylene glycol (PEG) head groups. Such synthetic PEG coated lipids exist in liquid form at room temperature and spontaneously form liposomes (nano type vesicles) upon hydration. In this work, we have focused on the band assignments for the spectra of single QuSomes^TMnano particles in pure form and in aqueous media acquired by means of Raman spectroscopy. In particular, we have found that the most prominent peaks in the studied spectral region are dominated by vibrational modes arising from C-C and C-H bonds. Furthermore, we have noticed that some of the distinct peaks observed below 1800 cm^-1 in pure sample are preserved in aqueous environment. These retained intense bands are located at 1449, 1128, 1079, and 1065 cm^-1. This effect might be due to the strong chain-chain interactions, because the chains have to orient themselves and become tightly packed in the vesicles wall rather than adopt random orientations in bulk. This technique has proven to be an excellent tool to establish the fingerprint region revealing the molecular structure and conformation of QuSomes^TM particles. The Raman spectroscopic data of these novel lipids and its vesicles formed in suspensions confirm high stability and are therefore considered as potential candidate for varieties of future applications including lipid based novel substances and drug delivery systems.

Proceedings Article | 11 August 2008 Paper

Temperature-controlled Raman microscopy to study the phase behavior of synthetic PEGylated lipids and nanovesicles

Rajan Bista, Reinhard Bruch, Aaron Covington, Alexander Sorger, Thoralf Gerstmann, Alexander Otto

Proceedings Volume 7099, 709904 (2008) https://doi.org/10.1117/12.804823

KEYWORDS: Raman spectroscopy, Thulium, Microscopes, Copper, Temperature metrology, Microscopy, Head, Scattering, Molecules, Infrared spectroscopy

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The study of phase transitions in lipids is important to understand various phenomena such as conformational order, trans-membrane diffusion, vesicle formation and fusion as well as drug-and protein-membrane interactions. Several techniques, including Raman spectroscopy, have previously been employed to investigate the phase behaviour of lipids. In this work, temperature-controlled Raman microscopy has been used to detect and analyze the phase transitions in two newly developed synthetic PEGylated lipids trademarked as QuSomes^TM and its nanovesicles in phosphate buffered saline (PBS) suspension. The amphiphiles considered in this study differ in their hydrophobic chain length and contain different units of polyethylene glycol (PEG) hydrophilic head groups. Raman spectra of these new artificial lipids and its nanovesicles have been recorded in the spectral range of 500-3100 cm^-1 by using a temperature-controlled sample holder attached to a Raman microscope. The gel to liquid-crystalline phase transitions of the sample lipids, composed of pure 1,2-dimyristoyl-rac-glycerol-3-dodecaethylene glycol (GDM-12) and 1,2-distearoyl-rac-glycerol-3-triicosaethylene glycol (GDS-23), have been detected by examining the changes in Raman spectra of the lipids caused by temperature variation. In the liquid phase both of the studied lipids spontaneously form liposomes (nanovesicles) upon hydration. In this study, we have demonstrated the efficacy of the temperature-controlled Raman microscope system to reveal the main phase transition temperature (T_m) profiles of our sample lipids and its nanovesicles in PBS suspension. The phase changes are detected by plotting peak intensity ratios in the C-H stretching region (~I₂₉₃₅/I₂₈₈₃) versus temperature. These ratios correlate with lateral or inter-chain interactions as well as intra-molecular interactions. In particular, we have found that phase transitions occur at a temperature of approximately 5.2°C and 21.2°C for pure GDM-12 and GDS-23, respectively. However, the phase transition temperature becomes significantly higher for lipid nanovesicles formed in aqueous suspensions. Such information about these PEG coated lipids might find applications in various studies including the development of lipid based novel substances and drug delivery systems.

Proceedings Article | 31 August 2005 Paper

Characterization of extreme ultraviolet (EUV) emission from xenon generated using a compact plasma-discharge source for lithography applications

H. Merabet, R. Bista, C. Schubert, S. Fuelling, R. Bruch, A. Godunov

Proceedings Volume 5918, 59180E (2005) https://doi.org/10.1117/12.613983

KEYWORDS: Xenon, Extreme ultraviolet, Ions, Plasma, Extreme ultraviolet lithography, Monochromators, Lithography, Grazing incidence, Light sources, Light

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