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Abstract The threat of emerging pathogens and microbial drug resistance has spurred tremendous efforts to develop new and more effective antimicrobial strategies. Recently, a novel ultrashort pulsed (USP) laser technology has been developed that enables efficient and chemical-free inactivation of a wide spectrum of viral and bacterial pathogens. Such a technology circumvents the need to introduce potentially toxic chemicals and could permit safe and environmentally friendly pathogen reduction, with a multitude of possible applications including the sterilization of pharmaceuticals and blood products, and the generation of attenuated or inactivated vaccines.

Abstract Background Gene therapy with plasmid DNA is emerging as a promising strategy for the treatment of many diseases. One of the major obstacles to such therapy is the poor transfection efficiency of DNA in vivo. Methods In this report, we employed a very low power, near-infrared femtosecond laser technique to enhance the transfection efficiency of intradermally and intratumorally administered DNA plasmid. Results We found that femtosecond laser treatment can significantly enhance the delivery of DNA into the skin and into established tumors in mice. In addition, we found that both laser power density as well as duration of laser treatment are critical parameters for augmenting DNA transfection efficiency. The femtosecond laser technique employs a relatively unfocused laser beam that maximizes the transfected area, minimizes damage to tissue and simplifies its implementation. Conclusion This femtosecond new laser technology represents a safe and innovative technology for enhancing DNA gene transfer in vivo.

Abstract Background Resonant microwave absorption has been proposed in the literature to excite the vibrational states of microorganisms in an attempt to destroy them. But it is extremely difficult to transfer microwave excitation energy to the vibrational energy of microorganisms due to severe absorption of water in this spectral range. We demonstrate for the first time that, by using a visible femtosecond laser, it is effective to inactivate viruses such as bacteriophage M13 through impulsive stimulated Raman scattering. Results and discussion By using a very low power (as low as 0.5 nj/pulse) visible femtosecond laser having a wavelength of 425 nm and a pulse width of 100 fs, we show that M13 phages were inactivated when the laser power density was greater than or equal to 50 MW/cm2. The inactivation of M13 phages was determined by plaque counts and had been found to depend on the pulse width as well as power density of the excitation laser. Conclusion Our experimental findings lay down the foundation for an innovative new strategy of using a very low power visible femtosecond laser to selectively inactivate viruses and other microorganisms while leaving sensitive materials unharmed by manipulating and controlling with the femtosecond laser system.

Abstract Background Recently, a technique which departs radically from conventional approaches has been proposed. This novel technique utilizes biological objects such as viruses as nano-templates for the fabrication of nanostructure elements. For example, rod-shaped viruses such as the M13 phage and tobacco mosaic virus have been successfully used as biological templates for the synthesis of semiconductor and metallic nanowires. Results and discussion Low wave number (≤ 20 cm-1) acoustic vibrations of the M13 phage have been studied using Raman spectroscopy. The experimental results are compared with theoretical calculations based on an elastic continuum model and appropriate Raman selection rules derived from a bond polarizability model. The observed Raman mode has been shown to belong to one of the Raman-active axial torsion modes of the M13 phage protein coat. Conclusion It is expected that the detection and characterization of this low frequency vibrational mode can be used for applications in nanotechnology such as for monitoring the process of virus functionalization and self-assembly. For example, the differences in Raman spectra can be used to monitor the coating of virus with some other materials and nano-assembly process, such as attaching a carbon nanotube or quantum dots.

Medical imaging methods have improved the detection of human diseases with increasing accuracy. The ability to probe molecular processes noninvasively or using tissue‐selective imaging agents and nanoparticles has made it possible to localize, identify the stage, and determine the functional status of pathological lesions. The challenges in detecting cancer particularly have driven the development of diverse imaging technologies. While earlier cancer imaging methods enabled preoperative evaluation, the need to track and visualize cancer location in the operating room itself has ushered in new systems capable of providing concurrent images of cancer during surgery. Intraoperative use of conventional clinical imaging modalities is often limited by bulky hardware design, prohibitive cost, lack of real‐time image display, and compatibility with conventional hardware interfaces. For these reasons, focus on fluorescence‐guided surgery (FGS) devices has increased to take advantage of real‐time, high‐resolution, functional imaging with hardware that has become increasingly amenable to miniaturization. In particular, the adaptation of wearable devices for FGS presents hands‐free capability for optimal navigation during cancer surgery. The evolution of head‐mounted devices in the operating room and adaptation for FGS is highlighted. Key challenges to wide clinical adoption of this imaging platform are identified and potential future directions are suggested. [ABSTRACT FROM AUTHOR]

Pathogen reduction is a viable approach to ensure the continued safety of the blood supply against emerging pathogens. However, the currently licensed pathogen reduction techniques are ineffective against non-enveloped viruses such as hepatitis A virus, and they introduce chemicals with concerns of side effects which prevent their widespread use. In this report, we demonstrate the inactivation of both enveloped and non-enveloped viruses in human plasma using a novel chemical-free method, a visible ultrashort pulsed laser. We found that laser treatment resulted in 2-log, 1-log, and 3-log reductions in human immunodeficiency virus, hepatitis A virus, and murine cytomegalovirus in human plasma, respectively. Laser-treated plasma showed ≥70% retention for most coagulation factors tested. Furthermore, laser treatment did not alter the structure of a model coagulation factor, fibrinogen. Ultrashort pulsed lasers are a promising new method for chemical-free, broad-spectrum pathogen reduction in human plasma. [ABSTRACT FROM AUTHOR]

Background Low-power ultrashort pulsed (USP) lasers operating at wavelengths of 425 nm and near infrared region have been shown to effectively inactivate viruses such as human immunodeficiency virus (HIV), M13 bacteriophage, and murine cytomegalovirus (MCMV). It was shown previously that non-enveloped, helical viruses such as M13 bacteriophage, were inactivated by a USP laser through an impulsive stimulated Raman scattering (ISRS) process. Recently, enveloped virus like MCMV has been shown to be inactivated by a USP laser via protein aggregation induced by an ISRS process. However, the inactivation mechanism for a clinically important class of viruses - non-enveloped, icosahedral viruses remains unknown. Results and discussions We have ruled out the following four possible inactivation mechanisms for non-enveloped, icosahedral viruses, namely, (1) inactivation due to ultraviolet C (UVC) photons produced by non-linear optical process of the intense, fundamental laser beam at 425 nm; (2) inactivation caused by thermal heating generated by the direct laser absorption/heating of the virion; (3) inactivation resulting from a one-photon absorption process via chromophores such as porphyrin molecules, or indicator dyes, potentially producing reactive oxygen or other species; (4) inactivation by the USP lasers in which the extremely intense laser pulse produces shock wave-like vibrations upon impact with the viral particle. We present data which support that the inactivation mechanism for non-enveloped, icosahedral viruses is the impulsive stimulated Raman scattering process. Real-time PCR experiments show that, within the amplicon size of 273 bp tested, there is no damage on the genome of MNV-1 caused by the USP laser irradiation. Conclusion We conclude that our model non-enveloped virus, MNV-1, is inactivated by the ISRS process. These studies provide fundamental knowledge on photon-virus interactions on femtosecond time scales. From the analysis of the transmission electron microscope (TEM) images of viral particles before and after USP laser irradiation, the locations of weak structural links on the capsid of MNV-1 were revealed. This important information will greatly aid our understanding of the structure of non-enveloped, icosahedral viruses. We envision that this non-invasive, efficient viral eradication method will find applications in the disinfection of pharmaceuticals, biologicals and blood products in the near future. [ABSTRACT FROM AUTHOR]

Background: Gene therapy with plasmid DNA is emerging as a promising strategy for the treatment of many diseases. One of the major obstacles to such therapy is the poor transfection efficiency of DNA in vivo. Methods: In this report, we employed a very low power, near-infrared femtosecond laser technique to enhance the transfection efficiency of intradermally and intratumorally administered DNA plasmid. Results: We found that femtosecond laser treatment can significantly enhance the delivery of DNA into the skin and into established tumors in mice. In addition, we found that both laser power density as well as duration of laser treatment are critical parameters for augmenting DNA transfection efficiency. The femtosecond laser technique employs a relatively unfocused laser beam that maximizes the transfected area, minimizes damage to tissue and simplifies its implementation. Conclusion: This femtosecond new laser technology represents a safe and innovative technology for enhancing DNA gene transfer in vivo. [ABSTRACT FROM AUTHOR]

The pathogenic bacterium Aeromonas hydrophila has been shown to exclusively utilize a ligand exchange mechanism for siderophore-mediated iron uptake, with a single nonspecific siderophore receptor facilitating iron exchange. However, the genes involved in this process, including the gene encoding the nonspecific receptor, are unknown. Here we identify and characterize a novel gene, nsr1, from A. hydrophila that encodes a putative protein with high homology and significant predicted structural similarities to the FhuA protein and other known ferric-siderophore receptors. This protein appears to localize on the cell membrane and is likely to be the receptor involved in the ligand exchange siderophore-mediated iron uptake mechanism of A. hydrophila. It is expected that this information may lead to the development of new antibiotics targeting either nsr1 or its gene product for use in controlling A. hydrophila infection. [ABSTRACT FROM AUTHOR]