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Contract number
14.Z50.31.0044 , 075-15-2021-617
Time span of the project
2018-2022

As of 01.11.2022

20
Number of staff members
25
scientific publications
6
Objects of intellectual property
General information

Name of the project: Photoacoustic technologies for early theranostics of metastatic tumors

Goals and objectives

Research directions: Developing photoacoustic technologies for early diagnostics and treatment of terminal diseases by non-invasive in vivo detection of biomarkets of those diseases circulating in blood in extremely small concentrations that are not detectable by existing methods

Project objective: Developing a new concept of early diagnostics and treatment of oncological diseases, infections and cardiovascular diseases with up to thousandfold sensitivity compared to existing methods.

The practical value of the study

Scientific results:

Within this project, we have developed a number of in vivo cytometers for working with laboratory animals, potentially, with patents:

  1. A stationary cytometer with an adjustable laser, the universal implementation of which allows to work with a suspension of tumor cells both in vitro and in vivo (in a flow of a model fluid in a polymer tube, in the blood streams of animals),
  2. A demonstration bench for a technology – a mobile cytometer for clinical tests.

Additionally, over the course of the existence of the Laboratory we have:

  1. Developed the principles and methods for building multifunctional  technological platform for photoacoustic flow cytometry (FAFC), including the creation of an experimental prototype and the development of software for the registration of moving absorbing objects with a focus on fast algorithms of analysis of pulse photoacoustic signals.
  2. Optimized the main modes and parameters of the FAFC platform on phantoms of blood cells and preclinical models of animals with a focus on the early diagnostics of circulating tumor cells, including the research of the possibility of therapy of circulating melanoma cells in vivo on mice with metastatic melanoma.
  3. Developed the principles and new methods of the optical clearing of biological tissues for the amplification of photoacoustic signals from blood vessels, including the creation of adequate phantoms of blood vessels and biological tissues, as well as the research of changes in the photoacoustic contrast of vessels in the process of using various methods of optical clearing of the skin.
  4. Developed multimodal high-contrast markers containing plasmonic nanoprobes and coloring agents, as well as studied the biological distribution of the developed contrast agents, conducted their functionalization to ensure a combination of the maximum possible photoacoustic response and the targeted delivery of an encapsulated anti-tumor drug.
  5. The results listed above, as well as others,  have been published in the world’s top journals: the leading scientist and the members of the research team have published 25 scientific articles in journals indexed by the Web of Science Core Collection database, of which 22 were published in journals of the first quartile (Q1). The conducted development has lead to the registration of 6 objects of intellectual property. Over the course of the implementation of the project the academic team has received more then 10 grants (Russian Science Foundation, scholarships of the President of the Russian Federation for studying abroad, Russian Foundation for Basic Research grants for postgraduates).

Implemented results of research:

The products and technologies developed within the project have been implemented at the preclinical level. The obtained fundamental scientific results are being continuously  developed, realized in the form of publications in highly-ranked academic journals. We are planning to implement our developments in applied domains in the medium and long term, pursuing the interests of the beneficiaries of the project ans the controlling bodies. 

Education and career development:

The Laboratory is aimed at both solving research problems and training professionals and retraining of highly qualified professionals who get acquainted with and develop the most state-of-the-art methods of optical and biomedical research, design unique new materials.

  • We have organized training on the use of equipment for conducting scientific research in the Laboratory for employees of the following organizations: Razumovskiy Saratov State Medical University (Russia), the Institute of Biochemistry and Physiology of Plants and Microorganisms of the Russian Academy of Sciences (Russia), the Skolkovo Institute of Science and Technology (Russia). The performers of the project actively participate in organizing the international school and conference «SARATOV FALL MEETING» that is staged on a regular basis.  
  • We have organized internships for employees of the Laboratory in the leading scientist’s laser laboratory at Arkansas Nanomedicine Center of the University of Arkansas for Medical Sciences (USA), including within the projects funded by Presidential scholarships of the Russian Federation won by the members of our team for conducting studying abroad.

Organizational and structural changes:

The Laboratory is a modern laboratory clinical complex furnished with equipment for developing optical devices and ultrasonic medical tools that is not present in any academic division of the Saratov region. This allows to conduct both unique scientific research and the development of scientific and medical equipment, testing its operation at various stages of preparation for preclinical and clinical testing and industrial production. Compared to the existing laboratories,  the capabilities of our Laboratory complex are unique, since they allow to solve complex problems related to the development of unique devices for photoacoustic diagnostics and conducting scientific research both for the problems of the development of scientific and medical devices and for a better understanding of the pathological processes occurring in the organism in the context of various socially significant diseases. 

Other results: We have organized the 20th specialized International Conference on Photoacoustic and Photothermal Phenomena, ICPPP 20, July 7–12, 2019, Moscow (Russia).

Collaborations:

  • University of Arkansas for Medical Sciences (USA): exchange of employees,  joint research and publications..
  • Razumovskiy Saratov State Medical University (Russia), Sechenov First Moscow State Medical University (Russia), Skolkovo Institute of Science and Technology (Russia), Institute of Biochemistry and Physiology of Plants and Microorganisms of the Russian Academy of Sciences (Russia): joint research  and publications.
  • IPG Photonics: industrial partner.

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m.a.juratli, y.a.menyaev, m.sarimollaoglu, e.siegel, d.a.nedosekin, w.c.culp, j.y.suen, e.i.galanzha, v.p.zharov.
Noninvasive label-free detection of circulating white and red blood clots in deep vessels with focused photoacoustic probe // Biomedical Optics Express, 2018, 9.
j.nolan, d.a.nedosekin, e.i.galanzha, v.p.zharov.
Detection of apoptotic circulating tumor cells using in vivo fluorescence flow cytometry // Cytometry Part A, 2018, 95(6).
m.v.novoselova, d.n.bratashov, m.sarimollaoglu, d.a.nedosekin, w.harringston, j.a.watts, m.han, b.n.khlebtsov, e.i.galanzha, d.a.gorin, v.p.zharov.
Giant photoacoustic effects at multilayered plasmon–dye interfaces // Journal of Biophotonics, 2019, 12(4).
e.a.genina, y.i.surkov, i.a.serebryakova, a.n.bashkatov, v.v. tuchin, v.p. zharov.
Rapid Ultrasound Optical Clearing of Human Light and Dark Skin // IEEE Trans Med Imaging, 2020, 39(10).
m.v. novoselova, t.o. abakumova, b.n. khlebtsov, t.s. zatsepina, e.n. lazareva, v.v. tuchin, v.p. zharov, d.a. gorin, e.i. galanzha.
Optical clearing for photoacoustic lympho- and angiography beyond conventional depth limit in vivo // Photoacoustics., 2020, 20.
kozlova, d. bratashov, o. inozemtseva, o. grishin, a. abdurashitov, e. prikhozhdenko, r. verkhovskii, e. shashkov, v. p. zharov.
Dynamic blood flow phantom for in vivo liquid biopsy standardization // Sci. Rep., 2020, 41598.
p.a. dyachenko (timoshina), l.e. dolotov, e.n. lazareva, a.a. kozlova, o.a. inozemtseva, r.a. verkhovskii, g.a. afanaseva, n.a. shushunova, v.v. tuchin, e.i. galanzha, v.p. zharov.
Detection of melanoma cells in whole blood samples using spectral imaging and optical clearing // IEEE Journal of Selected Topics in Quantum Electronics – 2020, 27(4).
n. besedina, v. chernyshev, o. efimova, p. rudakovskaya , m. novoselova, d. bratashov, r. chuprovnetochin, r. kamyshinsky, a. vasiliev, d. chermoshentsev, s. dyakov, v. zharov, n. gippius, d. gorin, a. yashchenok.
Gold Nanoparticle-Carbon Nanotube Multilayers on Silica Microspheres: Optoacoustic-Raman Enhancement and Potential Bioapplications // Materials Science & Engineering C., 2020, DOI: 10.1016/j.msec.2020.111736.
m.d. mokrousov, w.thompson, s.a. ermilov, t. abakumova, m.v. novoselova, o.a. inozemtseva, t.s. zatsepin, v.p. zharov, e.i. galanzha, d.a.
Gorin Indocyanine green dye based bimodal contrast agent tested by photoacoustic/fluorescence tomography setup // Biomedical Optics Express, 2021, 9.
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