Alexander S. Dvornikov

University of California, Irvine, Irvine, California, United States

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Publications (100)193.22 Total impact

  • Paolo Annibale · Alexander Dvornikov · Enrico Gratton
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    ABSTRACT: 3D orbital particle tracking is a versatile and effective microscopy technique that allows following fast moving fluorescent objects within living cells and reconstructing complex 3D shapes using laser scanning microscopes. We demonstrated notable improvements in the range, speed and accuracy of 3D orbital particle tracking by replacing commonly used piezoelectric stages with Electrically Tunable Lens (ETL) that eliminates mechanical movement of objective lenses. This allowed tracking and reconstructing shape of structures extending 500 microns in the axial direction. Using the ETL, we tracked at high speed fluorescently labeled genomic loci within the nucleus of living cells with unprecedented temporal resolution of 8ms using a 1.42NA oil-immersion objective. The presented technology is cost effective and allows easy upgrade of scanning microscopes for fast 3D orbital tracking.
    Biomedical Optics Express 06/2015; 6(6):2181. DOI:10.1364/BOE.6.002181 · 3.50 Impact Factor
  • Biophysical Journal 01/2015; 108(2):478a. DOI:10.1016/j.bpj.2014.11.2611 · 3.97 Impact Factor
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    ABSTRACT: In this paper we have used second harmonic generation (SHG) and phasor approach to auto fluorescence lifetime imaging (FLIM) to obtain fingerprints of different collagens and then used these fingerprints to observe bone marrow fibrosis in the mouse femur. This is a label free approach towards fast automatable detection of fibrosis in tissue samples. FLIM has previously been used as a method of contrast in different tissues and in this paper phasor approach to FLIM is used to separate collagen I from collagen III, the markers of fibrosis, the largest groups of disorders that are often without any effective therapy. Often characterized by an increase in collagen content of the corresponding tissue, the samples are usually visualized by histochemical staining, which is pathologist dependent and cannot be automated.
    Scientific Reports 01/2015; 5:13378. DOI:10.1038/srep13378 · 5.58 Impact Factor
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    ABSTRACT: Three-photon excitation fluorescence correlation spectroscopy was used to detect oligomerization equilibria of rat liver phosphofructokinase. The fluorescence intensity produced by the three photon excitation of tryptophan was collected using the DIVER microscope. In this home-built upright microscope, a large area photomultiplier, placed directly below the sample, is used as the detector. The lack of optical elements in the microscope detection path results in a significantly improved detection efficiency in the UV region down to about 300 nm, which encompasses the fluorescence emission from tryptophan. The three-photon excitation autocorrelation decays obtained for phosphofructokinase in presence of F6P showed the presence of large oligomers. Substitution of F6P with ATP in the buffer medium results in dissociation of the large oligomers, which is reported by the decreased autocorrelation amplitude. The three photon excitation process was verified from the slope of the log-log plot of intensity against laser power.
    The Journal of Physical Chemistry B 12/2014; 118(50). DOI:10.1021/jp511126x · 3.30 Impact Factor
  • Viera Crosignani · Sohail Jahid · Alexander Dvornikov · Enrico Gratton
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    ABSTRACT: We have developed a two-photon fluorescence microscope capable of imaging up to 4mm in turbid media with micron resolution. The key feature of this instrument is the innovative detector, capable of collecting emission photons from a wider surface area of the sample than detectors in traditional two-photon microscopes. This detection scheme is extremely efficient in the collection of emitted photons scattered by turbid media which allows eight fold increase in the imaging depth when compared with conventional two-photon microscopes. Furthermore, this system also has in-depth fluorescence lifetime imaging microscopy (FLIM) imaging capability which increases image contrast. The detection scheme captures emission light in a transmission configuration, making it extremely efficient for the detection of second harmonic generation (SHG) signals, which is generally forward propagating. Here we present imaging experiments of tissue phantoms and in vivo and ex vivo biological tissue performed with this microscope.
    Journal of Innovative Optical Health Sciences 09/2014; 07(05):1450034. DOI:10.1142/S1793545814500345 · 0.93 Impact Factor
  • Viera Crosignani · Sohail Jahid · Alexander S. Dvornikov · Enrico Gratton
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    ABSTRACT: We describe a novel two-photon fluorescence microscopy system capable of producing high-quality second harmonic generation (SHG) images in thick turbid media by using an innovative detection system. This novel detection system is capable of detecting photons from a very large surface area. This system has proven effective in providing images of thick turbid samples, both biological and artificial. Due to its transmission detection geometry, the system is particularly suitable for detecting SHG signals, which are generally forward directed. In this article, we present comparative data acquired simultaneously on the same sample with the forward and epidetection schemes. Microsc. Res. Tech., 2014. © 2014 Wiley Periodicals, Inc.
    Microscopy Research and Technique 05/2014; 77(5). DOI:10.1002/jemt.22354 · 1.17 Impact Factor
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    Sohail Jahid · Alexander S. Dvornikov · Michelle Digman · Enrico Gratton
    Biophysical Journal 01/2014; 106(2):400a. DOI:10.1016/j.bpj.2013.11.2255 · 3.97 Impact Factor
  • Viera Crosignani · Alexander Dvornikov · Enrico Gratton
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    ABSTRACT: We constructed an advanced detection system for two-photon fluorescence microscopy that allows us to image in biological tissue and tissue phantoms up to the depth of a few mm with micron resolution. The innovation lies in the detection system which is much more sensitive to low level fluorescence signals than the fluorescence detection configuration used in conventional two-photon fluorescence microscopes. A wide area photocathode photomultiplier tube (PMT) was used to detect fluorescence photons directly from a wide (1 inch diameter) area of the turbid sample, as opposed to the photon collection by the microscope objective which can only collect light from a relatively small area of the sample. The optical path between the sample and the photocathode is refractive index matched to curtail losses at the boundaries due to reflections. The system has been successfully employed in the imaging of tissue phantoms simulating brain optical properties and in biological tissues, such as murine small intestine, colon, tumors, and other samples. The system has in-depth fluorescence lifetime imaging (FLIM) capabilities and is also highly suitable for SHG signal detection, such as collagen fibers and muscles, due to the intrinsically forward-directed propagation of SHG photons.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2013; DOI:10.1117/12.2002101 · 0.20 Impact Factor
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    Viera Crosignani · Alexander Dvornikov · Enrico Gratton
    Biophysical Journal 01/2013; 104(2):336-. DOI:10.1016/j.bpj.2012.11.1868 · 3.97 Impact Factor
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    ABSTRACT: We describe a novel technical approach with enhanced fluorescence detection capabilities in twophoton microscopy that achieves deep tissue imaging, while maintaining micron resolution. Compared to conventional two-photon microscopy, greater imaging depth is achieved by more efficient harvesting of fluorescence photons propagating in multiple-scattering media. The system maintains the conventional two-photon microscopy scheme for excitation. However, for fluorescence collection the detection system harvests fluorescence photons directly from a wide area of the turbid sample. The detection scheme relies on a wide area detector, minimal optical components and an emission path bathed in a refractive-index-matching fluid that minimizes emission photon losses. This detection scheme proved to be very efficient, allowing us to obtain high resolution images at depths up to 3 mm. This technique was applied to in vivo imaging of the murine small intestine (SI) and colon. The challenge is to image normal and diseased tissue in the whole live animal, while maintaining high resolution imaging at millimeter depth. In Lgr5-GFP mice, we have been successful in imaging Lgr5-eGFP positive stem cells, present in SI and colon crypt bases.
    Journal of Biomedical Optics 11/2012; 17(11):116023. DOI:10.1117/1.JBO.17.11.116023 · 2.75 Impact Factor
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    ABSTRACT: Recently we described a novel technical approach with enhanced fluorescence detection capabilities in two-photon microscopy that achieves deep tissue imaging, while maintaining micron resolution. This technique was applied to in vivo imaging of murine small intestine and colon. Individuals with Inflammatory Bowel Disease (IBD), commonly presenting as Crohn's disease or Ulcerative Colitis, are at increased risk for developing colorectal cancer. We have developed a Giα2 gene knock out mouse IBD model that develops colitis and colon cancer. The challenge is to study the disease in the whole animal, while maintaining high resolution imaging at millimeter depth. In the Giα2-/- mice, we have been successful in imaging Lgr5-GFP positive stem cell reporters that are found in crypts of niche structures, as well as deeper structures, in the small intestine and colon at depths greater than 1mm. In parallel with these in vivo deep tissue imaging experiments, we have also pursued autofluorescence FLIM imaging of the colon and small intestine-at more shallow depths (roughly 160μm)- on commercial two photon microscopes with excellent structural correlation (in overlapping tissue regions) between the different technologies.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2012; DOI:10.1117/12.912841 · 0.20 Impact Factor
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    Viera Crosignani · Alexander Dvornikov · Enrico Gratton
    Biophysical Journal 01/2012; 102(3):199-. DOI:10.1016/j.bpj.2011.11.1086 · 3.97 Impact Factor
  • Viera Crosignani · Alexander S Dvornikov · Enrico Gratton
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    ABSTRACT: The depth of two-photon fluorescence imaging in turbid media can be significantly enhanced by the use of the here described fluorescence detection method that allows to efficiently collect scattered fluorescence photons from a wide area of the turbid sample. By using this detector we were able to perform imaging of turbid samples, simulating brain tissue, at depths up to 3 mm, where the two-photon induced fluorescence signal is too weak to be detected by means used in conventional two-photon microscopy.
    Journal of Biophotonics 03/2011; 4(9):592-9. DOI:10.1002/jbio.201100001 · 3.86 Impact Factor
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    Viera Crosignani · Alexander Dvornikov · Enrico Gratton
    Biophysical Journal 02/2011; 100(3). DOI:10.1016/j.bpj.2010.12.973 · 3.97 Impact Factor
  • A. S. DVORNIKOV · J. MALKIN · P. M. RENTZEPIS
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 11/2010; 25(48). DOI:10.1002/chin.199448022
  • Yongchao Liang · A. S. Dvornikov · P. M. Rentzepis
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 02/2010; 31(8). DOI:10.1002/chin.200008137
  • A S Dvornikov · E P Walker · P M Rentzepis
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    ABSTRACT: We describe the design and construction of ultrahigh capacity three-dimensional, 3D, optical storage devices that operate by two-photon absorption. The molecular systems and their properties that are used as two photon media for writing and one photon for accessing the stored information within the volume of the device are presented in some detail and the nonlinear two-photon absorption mechanism is briefly visited. The optical system and its components, which facilitated writing and reading, are also described and the bit density, bit error rate, store and access speeds, cycle times, and stability of the materials under various experimental conditions are also topics addressed in this review. The first ever storage of terabyte data in a removable storage disk is described in detail.
    The Journal of Physical Chemistry A 10/2009; 113(49):13633-44. DOI:10.1021/jp905655z · 2.78 Impact Factor
  • Jie Chen · Alexander S Dvornikov · Peter M Rentzepis
    The Journal of Physical Chemistry A 08/2009; 113(30):8818-9; discussion 8820-2. DOI:10.1021/jp809535q · 2.78 Impact Factor
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    A. S. Dvornikov · H. Zhang · P. M. Rentzepis
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    ABSTRACT: A new dye precursor (DP) molecule was synthesized and its photochromic, spectroscopic and kinetic properties were determined. This dye precursor yields the strongly fluorescent Rhodamine 700 dye when it is exposed to UV light. The ability to form a highly fluorescent dye was utilized in the fabrication of two-photon volumetric optical memory materials. The spectral characteristics, kinetics and photochemistry were measured and the photoreactions mechanism is proposed.
    Journal of Photochemistry and Photobiology A Chemistry 01/2009; 201(1):57-61. DOI:10.1016/j.jphotochem.2008.09.017 · 2.50 Impact Factor
  • Ed Walker · Alexander Dvornikov · Ken Coblentz · Peter Rentzepis
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    ABSTRACT: 1 Tbyte of data has been recorded in 200 layers inside the volume of one of our two-photon 3D disks. Each layer contains 5 Gb of data similar to the capacity of a single layer DVD. The results obtained with our high-performance 1.0 numerical aperture (NA) objective lens show a full disk recording of 1 Tbyte within a standard optical disk form factor 120 mm x 1.2 mm thick utilizing our very stable and efficient materials. Very high sensitivity materials are recorded with bit energies as low as 250 pJ/bit. Materials sensitive at 405 nm are experimentally tested by recording with a 405 nm Nichia laser diode. Results show that bit dimensions are further reduced, which enables future recordings of 5 Tbyte disk capacities by recording 25 Gb/layer, the equivalent of a Blu-ray disk capacity per layer.
    Applied Optics 09/2008; 47(22):4133-9. DOI:10.1364/AO.47.004133 · 1.78 Impact Factor