CURRENT RESEARCH PROGRAM

Dr. Renat Letfullin

e-mail: Letfullin@rose-hulman.edu

My research program is highly interdisciplinary and combines techniques from the fields of biophysics, nanomedicine, nanoscience, wave optics, laser physics, and aerosol physics, including optics of nanoparticles. Selected projects are mentioned below.

My research in the Biophysics area includes:

· A wave electrodynamics model of laser light interaction with nanosized biological scattering centers. This model describes the propagation of the wave into strongly scattering biological tissue based on the solution of the Maxwell wave equations. The primary scattering centers are thought to be the collagen fiber network of the extracellular matrix, the mitochondria, and other intracellular substructures, all with dimensions smaller than optical wavelengths. Another source of scattering centers is the artificially injected nanoparticles into the biotissue and the cells: liposomes (30-90 nm), gold nanoparticles (2-250 nm), neutral red-stained particles (30-500 nm), and polystyrene nanoparticles (30-80 nm).

· Exact diffraction simulations of the integral and differential optical properties of nanosized scattering centers below the diffraction limit. The amplitude-phase delay of an electromagnetic wave due to (1) scattering on the nanocenters described above and (2) the photo-thermal-induced inhomogeneities of the medium, is calculated on the basis of the wave equation and Mie diffraction theory. I conduct exact diffraction calculations of the integral and differential nanoparticle optical properties (such as scattering, absorption, attenuation cross sections, and scattering amplitude functions) below the diffraction limit for a broad range of the Mie parameter and temperature intervals.

· Non-destructive optical techniques for diagnostics of the biological/particle nanostructures. One technique is two-color laser transmissometry. Another technique for phase control of the nanoparticles characteristics is based on the interference strips displacement method, which can be realized with asymmetric Mach-Zehnder interferometer.

· Theoretical model for laser heating and evaporation of nanostructures and biological tissue. This model takes into account the temperature dependences of the optical and thermo-physical parameters of the particles and surrounding medium, as well as the real-time shape of the laser pulse. These calculations can be performed at different heat-mass transfer modes, such as the free molecular and diffusion modes.

· Laser Ablation and Optical Damage of the Cancer Cells by Nanoparticles. The characteristics of laser-induced cell damage depend on the rates of the basic processes taking place in the heated biological system containing the nanoparticles. These include the rates of the tissue inflammation – the first damage stage, the rates of the cancerous cells necrosis – the second damage stage, and the rates of evaporation and carbonizing of the cancer cells – the third damage stage. I develop an effective kinetic model of cancer-cell killing by laser-activated nanoheaters, which will include the most important physical-chemical kinetic and biological features. This model will predict the damage depth and the exposure time for each stage of laser/nanoparticle damage.

My research in the Nanomedicine area includes development of the Theory and Simulation Techniques for Selective Cancer Nanotherapy:

· Surface plasmon resonance as a cancer biomarker detection technology. Surface plasmon resonance (SPR) has been investigated both for its fundamental importance and as a possible detection technique with biochemical applications. Recently, commercial biosensors have become available that rely on SPR for detecting various proteins and other DNA constituents. Together with undergraduate students I perform simulations of the integral and differential optical properties (such as scattering, absorption and attenuation cross sections and scattering amplitude functions) of nanoparticles below the diffraction limit for a broad range of the wavelengths of transverse electromagnetic waves.

· Ultrashort laser pulse heating of nanostructures in cancer cells. Two models will be studied by the PI/co-PI to describe ultrashort laser pulse interactions with metal nanoparticles in time. The first is a two-temperature model which involves fast thermalization within the electron subsystem, non-uniform energy transfer to the lattice, and electron energy losses due to electron heat transport into the particle volume. The second is a one-temperature model based on a heat transfer equation written within a uniform heating approximation throughout the particle volume. Along with and participating students I perform the comparative simulations of temperature-time dynamics using these models for laser heating of metallic nanotargets in the femtosecond, picosecond and nanosecond regimes, thus providing an effective modeling method to explore the effects playing the determining role in the laser-matter interactions.

· Laser-induced explosion of nanoparticles. The strongly-enhanced SPR of noble metal nanoparticles at optical frequencies makes them excellent scatters and absorbers of visible and near-IR light. When the strongly-absorbing nanoparticles are irradiated by ultrashort laser pulses, their temperature rapidly reaches the thresholds for nonlinear effects and can cause an explosion of nanoparticles. This involves the generation of a shock wave of dense vapors expanding in the cell volume with supersonic velocity, producing sound waves and optical plasma. A phenomenological picture of these complex physical effects is shown schematically in Fig. 1.

Figure 1. Laser-induced thermal explosion of a nanoparticle.

There are two main physical mechanisms that could lead to the laser-induced explosion of nanoparticles - (a) thermal explosion mode through electron-phonon excitation-relaxation and (b) Coulomb explosion mode through multiphoton ionization. I simulate the threshold laser energy density required for the realization of the thermal explosion of nanoparticles.

New Dynamic Modes in Selective Cancer Nanomedicine:

· Microbubble overlapping mode. Bioconjugated nanoparticles are selectively attached to chosen cellular targets, in particular to membrane receptors activated by other antibodies as shown in Fig. 2. When nanoparticles are irradiated by short laser pulses, they absorb the laser radiation and their temperature rises very quickly, reaching up to the threshold of microbubble formation in the surrounding liquid medium.

I’m studying a new dynamic mode for selective cancer treatment that involves the overlapping of bubbles inside the cell volume (shown in bottom part of Fig. 2). The microbubble overlapping mode around intracellular structures induced by short laser pulses can dramatically increase the efficiency of the cancer treatment as a result of the larger damage range and higher expenditure rate in comparison to a thermal damage mode.

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