Pathogen Reduction in Human Plasma Using an Ultrashort Pulsed Laser

Tsen, Shaw Wei D; Kingsley, David H.; Kibler, Karen V.; Jacobs, Bert; Sizemore, Sara M.; Vaiana, Sara M.; Anderson, Jeanne; Tsen, Kong-Thon; Achilefu, Samuel

doi:10.1371/journal.pone.0111673

Cited by 8 publications

(13 citation statements)

References 27 publications

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“…Ultrashort pulse laser (USPL) light treatments were previously shown to be capable of inactivating murine norovirus (MNV) and other viruses [ 42 , 45 , 47 – 49 ]. Impulsive stimulated Raman scattering (ISRS) was the postulated inactivation mechanism [ 43 , 44 , 46 ]. Essentially the ISRS hypothesis was that high frequency resonance vibrations are potentially induced by the 425 nm USPL, with a bandwidth of 420–430 nm, that may be capable of causing vibrations of sufficient strength that the capsid is destroyed after nonthermal treatments of an hr.…”

Section: Introductionmentioning

confidence: 99%

Oxygen-dependent laser inactivation of murine norovirus using visible light lasers

Kingsley¹,

Kuis

Pérez³

et al. 2018

Virol J

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BackgroundPrevious work indicated that an ultrashort pulse (USP) 425 nm laser is capable of inactivating murine norovirus (MNV: Virol. J. 11:20), perhaps via an impulsive stimulated Raman scattering (ISRS) mechanism, and does not substantially damage human plasma proteins (PLOS One 9:11). Here, further investigation of virus inactivation by laser light is performed.MethodsIn this study, we evaluate whether inactivation of MNV is specific to the USP wavelength of 425 nm, or if it occurs at other visible wavelengths, using a tunable mode-locked Ti-Sapphire laser that has been frequency doubled to generate femtosecond pulses at wavelengths of 400, 408, 425, 450, 465, and 510 nm. Continuous Wave (CW) lasers are also applied. Singlet oxygen enhancers are used to evaluate the sensitivity of MNV to singlet oxygen and oxygen quenchers are used to evaluate effects on virus inactivation as compared to untreated controls.Results> 3 log10 inactivation of MNV pfu occurs after irradiation with an average power of 150 mW at wavelengths of 408, 425 or 450 nm femtosecond-pulsed light for 3 h. Thus results suggest that the mechanism by which a laser inactivates the virus is not wavelength-specific. Furthermore, we also show that irradiation using a continuous wave (CW) laser of similar power at 408 nm also yields substantial MNV inactivation indicating that inactivation does not require a USP. Use of photosensitizers, riboflavin, rose bengal and methylene blue that generate singlet oxygen substantially improves the efficiency of the inactivation. The results indicate a photochemical mechanism of the laser-induced inactivation where the action of relatively low power blue laser light generates singlet oxygen.ConclusionResults suggest formation of short-lived reactive oxygen species such as singlet oxygen by visible laser light as the cause of virus inactivation rather than via an ISRS mechanism which induces resonant vibrations.

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Section: Introductionmentioning

confidence: 99%

Oxygen-dependent laser inactivation of murine norovirus using visible light lasers

Kingsley¹,

Kuis

Pérez³

et al. 2018

Virol J

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“…For instance, irradiation of a visible USP laser can (1) significantly reduce pathogen infectivity, while retaining ≥ 70% of most of the coagulation factors in human plasma [22]; (2) inactivate enveloped viruses through laser-driven aggregation of viral capsid proteins without altering the structure of surface proteins -- hemagglutinin, leading to the very efficient generation of USP laser-inactivated whole influenza virus vaccines [23,24]. In this report, we show that, in addition to bacteria and viruses, visible USP laser treatment can efficiently inactivate mycoplasma and yeast, which are major cell culture contaminants, with good preservation of the viability of mammalian cell lines.…”

Section: Introductionmentioning

confidence: 99%

Selective Photonic Disinfection of Cell Culture Using a Visible Ultrashort Pulsed Laser

Tsen

Kibler

Jacobs

et al. 2016

IEEE J. Select. Topics Quantum Electron.

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Microbial contamination of cell culture is a major problem encountered both in academic labs and in the biotechnology/pharmaceutical industries. A broad spectrum of microbes including mycoplasma, bacteria, fungi, and viruses are the causative agents of cell culture contamination. Unfortunately, the existing disinfection techniques lack selectivity and/or lead to the development of drug-resistance, and more importantly there is no universal method to address all microbes. Here, we report a novel, chemical-free visible ultrashort pulsed laser method for cell culture disinfection. The ultrashort pulsed laser technology inactivates pathogens with mechanical means, a paradigm shift from the traditional pharmaceutical and chemical approaches. We demonstrate that ultrashort pulsed laser treatment can efficiently inactivate mycoplasma, bacteria, yeast, and viruses with good preservation of mammalian cell viability. Our results indicate that this ultrashort pulsed laser technology has the potential to serve as a universal method for the disinfection of cell culture.

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“…It is important to recall that the inactivation by fs-laser treatment varies depending on the type of bacteriophage and the excitation wavelength. Table 3 summarizes the time required for each excitation wavelength to achieve log reduction Past works have proposed ISRS as the underlying mechanism for the inactivation of bacteriophages [9,11,14,21] and viruses [10,11,14,16,18]. A distinct characteristic of ISRS is the dependence of its efficiency on the pulse duration of the driving laser.…”

Section: F I G U R E 1 Load Reduction Of the Ms2 And M13mentioning

confidence: 99%

“…This ζ-potential is a key indicator of the stability of colloidal dispersions, and its magnitude indicates the degree of electrostatic repulsion between adjacent, similarly charged particles, and its conformation, in a dispersion and thus may impact inactivation. Recent studies highlight that viral inactivation observed during fs-laser therapy is related to changes in the capsid of viruses [9][10][11][12][13][14][15][16][17][18]. Inactivation by laser treatment is the result of a complex succession of athermic interaction mechanisms between the laser pulse and the biological material.…”

Section: Inactivation Of Bacteriophages Ms2 and M13 In Different DImentioning

confidence: 99%

“…To surmount this unfavorable energy barrier in capsid disassembly for inactivation, ultrafast visible and near-infrared (NIR) lasers have been effective via a process attributed to Impulsive Stimulated Raman Scattering (ISRS) effect [9][10][11][12][13][14][15][16][17][18]. Such inactivation by femtosecond lasers is efficient, easily implemented onto, for example, manufacturing lines, and relatively inexpensive.…”

Section: Introductionmentioning

confidence: 99%

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Comparative study on the inactivation of MS2 and M13 bacteriophages using energetic femtosecond lasers

Berchtikou

Sokullu

Nahar

et al. 2020

Journal of Biophotonics

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Femtosecond (fs) laser irradiation techniques are emerging tools for inactivating viruses that do not involve ionizing radiation. In this work, the inactivation of two bacteriophages representing protective capsids with different geometric constraints, that is, the near-spherical MS2 (with a diameter of 27 nm) and the filamentous M13 (with a length of 880 nm) is compared using energetic visible and near-infrared fs laser pulses with various energies, pulse durations, and exposure times. Intriguingly, the results show that inactivation using 400 nm lasers is substantially more efficient for MS2 compared to M13. In contrast, using 800 nm lasers, M13 was slightly more efficiently inactivated. For both viruses, the genome was exposed to a harmful environment upon fs-laser irradiation. However, in addition to the protection of the genome, the metastable capsids differ in many properties required for stepwise cell entry that may explain their dissimilar behavior after (partial) disassembly. For MS2, the dominant mechanism of fs-laser inactivation was the aggregation of the viral capsid proteins, whereas aggregation did not affect M13 inactivation, suggesting that the dominant mechanism of M13 inactivation was related to breaking of secondary protein links. K E Y W O R D S aggregation of the viral capsid proteins, femtosecond lasers, inactivation, mechanism of femtosecond-laser inactivation, MS2 and M13 bacteriophages

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Pathogen Reduction in Human Plasma Using an Ultrashort Pulsed Laser

Cited by 8 publications

References 27 publications

Oxygen-dependent laser inactivation of murine norovirus using visible light lasers

Oxygen-dependent laser inactivation of murine norovirus using visible light lasers

Selective Photonic Disinfection of Cell Culture Using a Visible Ultrashort Pulsed Laser

Comparative study on the inactivation of MS2 and M13 bacteriophages using energetic femtosecond lasers

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