Project 1. Synthesis and Photophysical Property Investigation of Visible-light Emitting Silicon Nanoparticles (Si NPs)
Rationale: Because silicon is biologically well tolerated and extremely important in electronics, development of photoluminescent Si nanoparticles with color-tunable emission and covalently modified surface for matrix compatibility will lead to biologically and environmentally friendly fluorophores, which are additionally compatible with existing silicon-based electronics (leading to integration of electronic and optical properties in pure Si-based devices)
Broad Goal: To fundamentally understand the origin(s) of luminescence in nanostructured silicon to facilitate emission color tuning for imaging and opto-electronic applications (e.g., LEDs).
Recent Highlight: My lab synthesizes Si NPs by novel as well as literature methods, manipulates them for colloidal and photophysical property stability in aqueous environments, and examines their photophysical and chemical property changes in response to various analytes and solution environments. For example, we have synthesized and demonstrated long-term stable, red photoluminescent Si NPs as fluorescent imaging agents in complex aqueous and biochemical media, which is a noteworthy achievement since red-to-near-IR emitting fluorophores are most desirable for biological imaging (avoiding tissue interference of the imaging agent signal) and since aqueous Si NPs have typically been blue-emitting.(see DOI: 10.1557/jmr.2012.377)
Project 2. Synthesis and Biological Compatibility Study of Ultra-high Payload Bismuth Nanoparticle (Bi NP) X-ray Contrast Agents
Rationale: Bismuth has the heaviest, stable isotope of any element on the periodic table, and despite being a heavy metal it is exceptionally well tolerated in vivo. Since X-ray attenuation is based on atomic number (the higher Z, the greater the attenuation) as well as the density and thickness of the absorber, a collection of several hundred Bi atoms in a nanoparticle should provide exceptional attenuation properties. Furthermore, the high surface area of these particles allows for surface modification with biological targeting groups to facilitate targeted imaging. We have in mind that this kind of reagent would be particularly useful in finding metastatic tumor sites by non-invasive, X-ray inspection.
Broad Goal: To demonstrate that heavy metal nanoparticles can be targeted to biological structures, which will then be visible by conventional X-ray imaging (soft tissue structures, such as tumors, do not show up particularly well in X-rays because they are composed of low Z elements).
Recent Highlight: My lab synthesizes highly X-ray opaque Bi NPs by novel methods, optimizes them for colloidal and redox stability in aqueous environments, and examines their qualitative and quantitative X-ray opacity and cyto-combatibility. Taking advantage of the high atomic number (Z = 83) of Bi and the Z4 dependence of X-ray opacity, we have worked to improve the X-ray opaque payload per unit of contrast material relative to clinical molecular reagents, literature examples of nanoscale X-ray contrast materials, and our own examples of nanoscale X-ray contrast materials. For example, we increased the core size and improved the ratio of surface coating:X-ray opaque Bi NP core from 130:20 to 86:74, an over 200-hundred fold increase (based on % Bi by volume) in the dense, X-ray opaque core loading. Furthermore, in collaboration with Dr. David Cormode at the University of Pennsylvania Perelman School of Medicine (joint appointments in Radiology and Chemistry Departments), we have accomplished high resolution, quantitative computed tomography (CT) attenuation measurements on our X-ray opaque Bi NPs in comparison to iodine-based agents. Our Bi NPs show enhanced X-ray contrast in a clinically relevant setting relative to the iodinated contrast agent, and furthermore, cellular toxicity assays indicate high biocompatibility potential for these Bi NPs.(see DOI: 10.1021/cm500077z)
Project 3. Mechanistic Insight and Quantitative Sensing of Commercially Available CdSe@ZnS Core@Shell Quantum Dots (QDs) for Targeted Placement and Localized Sensing of Serotonin (5-HT) Neurotransmitter (A collaboration with Tania Vu, Oregon Health & Science University)
Rationale: Carrier transfer (e- or h+) from the photogenerated excitons (e-/h+ pair) of QDs to small molecules near their surfaces results in QD luminescence intensity decrease; and according to our preliminary results, the rate of intensity loss can be correlated to nanomolar concentrations of serotonin. It is known that single QDs can be targeted to single serotonin receptors in the native environments of live neurons; thus, these QD sensors will have the ability to measure local serotonin concentration and local concentration imbalances at the sites of serotonin release (where imbalances are suspected to be primary or contributing causes of a broad range of psychiatric disorders/ mental illnesses).
Broad Goal: Our long term goal is to develop a family of fluorescent QD nanosensors based on neurotransmitter-specific photodegradation mechanisms in order to measure minute (<nM), localized quantities of neurotransmitters in spatially confined nano-environments, (i.e., synapses).
Recent Highlight: In collaboration with the Vu lab (Oregon Health & Science University, Dept of Biomedical Engineering), we have identified an analyte concentration-dependent decrease in red-emitting CdSe@ZnS Quantum Dot (QD) photoluminescence intensity in response to nM-to-M concentrations of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Spectroscopic evidence indicates that a Photoinduced Charge (e-/h+) Transfer is the mechanism responsible for the observed decrease in QD emission intensity. We have calibrated this response in solution, ensemble QD studies and in in vitro, single QD studies.(manuscript submitted)