Timothy J. Russin

Near-Infrared Emitting Fluorophore-Doped Calcium Phosphate Nanoparticles for In Vivo Imaging of Human Breast Cancer

Early detection is a crucial element for the timely diagnosis and successful treatment of all human cancers but is limited by the sensitivity of current imaging methodologies. We have synthesized and studied bioresorbable calcium phosphate nanoparticles (CPNPs) in which molecules of the near-infrared (NIR) emitting fluorophore, indocyanine green (ICG), are embedded. The ICG-CPNPs demonstrate exceptional colloidal and optical characteristics. Suspensions consisting of 16 nm average diameter particles are colloidally stable in physiological solutions (phosphate buffered 0.15 M saline (PBS), pH 7.4) with carboxylate or polyethylene glycol (PEG) surface functionality. ICG-doped CPNPs exhibit significantly greater intensity at the maximum emission wavelength relative to the free constituent fluorophore, consistent with the multiple molecules encapsulated per particle. The quantum efficiency per molecule of the ICG-CPNPs is 200% greater at 0.049 +/- 0.003 over the free fluorophore in PBS. Photostability based on fluorescence half-life of encapsulated ICG in PBS is 500% longer under typical clinical imaging conditions relative to the free dye. PEGylated ICG-CPNPs accumulate in solid, 5 mm diameter xenograft breast adenocarcinoma tumors via enhanced retention and permeability (EPR) within 24 h after systemic tail vein injection in a nude mouse model. Ex situ tissue imaging further verifies the facility of the ICG-CPNPs for deep-tissue imaging with NIR signals detectable from depths up to 3 cm in porcine muscle tissue. Our ex vivo and in vivo experiments verify the promise of the NIR CPNPs for diagnostic imaging in the early detection of solid tumors.

Encapsulation of Organic Molecules in Calcium Phosphate Nanocomposite Particles for Intracellular Imaging and Drug Delivery

Encapsulation of imaging agents and drugs in calcium phosphate nanoparticles (CPNPs) has potential as a nontoxic, bioresorbable vehicle for drug delivery to cells and tumors. The objectives of this study were to develop a calcium phosphate nanoparticle encapsulation system for organic dyes and therapeutic drugs so that advanced fluoresence methods could be used to assess the efficiency of drug delivery and possible mechanisms of nanoparticle bioabsorption. Highly concentrated CPNPs encapsulating a variety of organic fluorophores were successfully synthesized. Well-dispersed CPNPs encapsulating Cy3 amidite exhibited nearly a 5-fold increase in fluorescence quantum yield when compared to the free dye in PBS. FCS diffusion data and cell staining were used to show pH-dependent dissolution of the particles and cellular uptake, respectively. Furthermore, an experimental hydrophobic cell growth inhibitor, ceramide, was successfully delivered in vitro to human vascular smooth muscle cells via encapsulation in CPNPs. These studies demonstrate that CPNPs are effective carriers of dyes and drugs for bioimaging and, potentially, for therapeutic intervention.

Probing graphene edges via Raman scattering.

We present results of a Raman scattering study from the region near the edges of n-graphene layer films. We find that a Raman band (D) located near 1344 cm(-1) (514.5 nm excitation) originates from a region next to the edge with an apparent width of approximately 70 nm (upper bound). The D-band was found to exhibit five important characteristics: (1) a single Lorentzian component for n = 1, and four components for n = 2-4, (2) an intensity I(D) approximately cos(4) theta, where theta is the angle between the incident polarization and the average edge direction, (3) a local scattering efficiency (per unit area) comparable to the G-band, (4) dispersive behavior ( approximately 50 cm(-1)/eV for n = 1), consistent with the double resonance (DR) scattering mechanism, and (5) a scattering efficiency that is almost independent of the crystallographic orientation of the edge. High-resolution transmission electron microscope images reveal that our cleaved edges exhibit a sawtooth-like roughness of approximately 3 nm (i.e., approximately 20 times the C-C bond length). We propose that in the double resonance Raman scattering process the photoelectron scatters diffusely from our edges, obscuring the recently proposed strong variation in the scattering from armchair versus zigzag symmetry edges based on theoretical arguments.

A Computer-Controlled Classroom Model of an Atomic Force Microscope

The concept of “seeing by feeling” as a way to circumvent limitations on sight is universal on the macroscopic scale—reading Braille, feeling ones way around a dark room, etc. The development of the atomic force microscope(AFM) in 1986 extended this concept to imaging in the nanoscale. While there are classroom demonstrations that use a tactile probe to map the topography or some other property of a sample, the rastering of the probe over the sample is manually controlled, which is both tedious and potentially inaccurate. Other groups have used simulation or tele-operation of an AFM probe. In this paper we describe a teaching AFM with complete computer control to map out topographic and magnetic properties of a “crystal” consisting of two-dimensional arrays of spherical marble “atoms.” Our AFM is well suited for lessons on the “Big Ideas of Nanoscale” such as tools and instrumentation, as well as a pre-teaching activity for groups with remote access AFM or mobile AFM. The principle of operation of our classroomAFM is the same as that of a real AFM, excepting the nature of the force between sample and probe.