Quantum Dot Fluorescent Imaging: Using Atomic Structure Correlation Studies to Improve Photophysical Properties.

Efforts to study intricate, higher-order cellular functions have called for fluorescence imaging under physiologically relevant conditions such as tissue systems in simulated native buffers. This endeavor has presented novel challenges for fluorescent probes initially designed for use in simple buffers and monolayer cell culture. Among current fluorescent probes, semiconductor nanocrystals, or quantum dots (QDs), offer superior photophysical properties that are the products of their nanoscale architectures and chemical formulations.

Quantitative morphological analysis of InP-based quantum dots reveals new insights into the complexity of shell growth.

The incorporation of quantum dots in display technology has fueled a renewed interest in InP-based quantum dots, but difficulty controlling the Zn chemistry during shelling has stymied thick, even ZnSe shell growth. The characteristic uneven, lobed morphology of Zn-based shells is difficult to assess qualitatively and measure through traditional methods. Here, we present a methodological study utilizing quantitative morphological analysis of InP/ZnSe quantum dots to analyze the impact of key shelling parameters on InP core passivation and shell epitaxy.

Minimizing the Reorganization Energy of Cobalt Redox Mediators Maximizes Charge Transfer Rates from Quantum Dots.

Light-induced charge separation is at the very heart of many solar harvesting technologies. The reduction of energetic barriers to charge separation and transfer increases the rate of separation and the overall efficiency of these technologies. Here we report that the internal reorganization energy of the redox acceptor, the movement of the atoms with changing charge, has a profound effect on the charge transfer rates from donor quantum dots.

Ultrafast spectroscopy studies of carrier dynamics in semiconductor nanocrystals.

Semiconductor nanocrystals have become ubiquitous both in scientific research and in applied technologies related to light. When a nanocrystal absorbs a photon an electron-hole pair is created whose fate dictates whether the nanocrystal will be suitable for a particular application. Ultrafast spectroscopy provides a real-time window to monitor the evolution of the electron-hole pair.

Fluorescent Colloidal Ferroelectric Nanocrystals.

We report the appearance of ferroelectric behavior arising from a room-temperature cation exchange of cadmium-based semiconductor nanoparticles. Fluorescence retention was achieved through protective CdS shelling before cation exchange with tin(IV) by containing defects in the CdS shell rather than the fluorescent CdSe cores. Ferroelectric response, measured using a Sawyer-Tower circuit, was kept constant, while fluorescence retention increases with an increase in the number of CdS monolayers.

A Novel Biotinylated Homotryptamine Derivative for Quantum Dot Imaging of Serotonin Transporter in Live Cells.

The serotonin transporter (SERT) is the primary target for selective serotonin reuptake inhibitor (SSRI) antidepressants that are thought to exert their therapeutic effects by increasing the synaptic concentration of serotonin. Consequently, probes that can be utilized to study cellular trafficking of SERT are valuable research tools. We have developed a novel ligand (IDT785) that is composed of a SERT antagonist (a tetrahydro pyridyl indole derivative) conjugated to a biotinylated poly ethylene glycol (PEG) via a phenethyl linker.

Membrane Nanoscopic Organization of D2L Dopamine Receptor Probed by Quantum Dot Tracking.

The role of lateral mobility and nanodomain organization of G protein-coupled receptors in modulating subcellular signaling has been under increasing scrutiny. Investigation of D2 dopamine receptor diffusion dynamics is of particular interest, as these receptors have been linked to altered neurotransmission in affective disorders and represent the primary target for commonly prescribed antipsychotics. Here, we applied our single quantum dot tracking approach to decipher intrinsic diffusion patterns of the wild-type long isoform of the D2 dopamine receptor and its genetic variants previously identified in several cohorts of schizophrenia patients.

Enlightened: addressing circadian and seasonal changes in photoperiod in animal models of bipolar disorder.

Bipolar disorders (BDs) exhibit high heritability and symptoms typically first occur during late adolescence or early adulthood. Affected individuals may experience alternating bouts of mania/hypomania and depression, with euthymic periods of varying lengths interspersed between these extremes of mood. Clinical research studies have consistently demonstrated that BD patients have disturbances in circadian and seasonal rhythms, even when they are free of symptoms.

Rate of change in solar insolation is a hidden variable that influences seasonal alterations in bipolar disorder.

The consensus in the literature is that bipolar disorder is seasonal. We argue that there is finer detail to seasonality and that changes in mood and energy in bipolar disorder are dictated by the rate of change of solar insolation.

Optical and electrochemical tuning of hydrothermally synthesized nitrogen-doped carbon dots.

Carbon dots (CDs) are a rapidly progressing class of nanomaterial which show promise towards applications in solar energy conversion due to their low toxicity, favorable electrochemical properties, and tunability. In recent years there have been a number of reported CD syntheses, both top-down and bottom-up methods, producing a diverse range of CDs with intrinsic properties dependent on the starting materials and utilized dopants. This work presents a citrate buffer-facilitated synthesis of nitrogen-doped carbon dots (NCD) and explores the impact of urea concentration on observed electrochemical and optical properties.

Single Quantum Dot Tracking Unravels Agonist Effects on the Dopamine Receptor Dynamics.

D2 dopamine receptors (DRD2s) belong to a family of G protein-coupled receptors that modulate synaptic dopaminergic tone via regulation of dopamine synthesis, storage, and synaptic release. DRD2s are the primary target for traditional antipsychotic medications; dysfunctional DRD2 signaling has been linked to major depressive disorder, attention-deficit hyperactivity disorder, addiction, Parkinson's, and schizophrenia. DRD2 lateral diffusion appears to be an important post-translational regulatory mechanism; however, the dynamic response of DRD2s to ligand-induced activation is poorly understood.

Seasonal effects on bipolar disorder: A closer look.

Bipolar disorders have an onset in late adolescence or early adulthood and patients may experience alternating episodes of mania and depression, with euthymic periods interspersed between these extremes of mood. Clinical research studies have shown that bipolar disorder patients exhibit disruptions in circadian and seasonal rhythms, even when they are symptom free. In addition, some bipolar patients display pronounced seasonal patterns in occurrence of manic and depressive episodes, time of year for disease onset, and age of onset.

Effect of indium alloying on the charge carrier dynamics of thick-shell InP/ZnSe quantum dots.

Thick-shell InP/ZnSe III-V/II-VI quantum dots (QDs) were synthesized with two distinct interfaces between the InP core and ZnSe shell: alloy and core/shell. Despite sharing similar optical properties in the spectral domain, these two QD systems have differing amounts of indium incorporation in the shell as determined by high-resolution energy-dispersive x-ray spectroscopy scanning transmission electron microscopy. Ultrafast fluorescence upconversion spectroscopy was used to probe the charge carrier dynamics of these two systems and shows substantial charge carrier trapping in both systems that prevents radiative recombination and reduces the photoluminescence quantum yield.

Labeling Neuronal Proteins with Quantum Dots for Single-Molecule Imaging.

Single-molecule imaging has illuminated dynamics and kinetics of neuronal proteins in their native membranes helping us understand their effective roles in the brain. Here, we describe how nanometer-sized fluorescent semiconductors called quantum dots (QD) can be used to label neuronal proteins in a single QD imaging format. We detail two generalizable protocols accompanied by experimental considerations giving the user options in approach tailored to the materials and equipment available.

Quantitative Analysis of Single Quantum Dot Trajectories.

Single quantum dot tracking (SQDT) is a powerful technique for interrogating biomolecular dynamics in living cells and tissue. SQDT has particularly excelled in driving discovery at the single-molecule level in the fields of neuronal communication, plasma membrane organization, viral infection, and immune system response. Here, we briefly characterize various elements of the SQDT analytical framework and provide the reader with a detailed set of executable commands to implement commonly used algorithms for SQDT data processing.

Ligand-conjugated quantum dots for fast sub-diffraction protein tracking in acute brain slices.

Semiconductor quantum dots (QDs) have demonstrated utility in long-term single particle tracking of membrane proteins in live cells in culture. To extend the superior optical properties of QDs to more physiologically relevant cell platforms, such as acute brain slices, we examine the photophysics of compact ligand-conjugated CdSe/CdS QDs using both ensemble and single particle analysis in brain tissue media. We find that symmetric core passivation is critical for both photostability in oxygenated media and for prolonged single particle imaging in brain slices.

Quantum dots reveal heterogeneous membrane diffusivity and dynamic surface density polarization of dopamine transporter.

The presynaptic dopamine transporter mediates rapid reuptake of synaptic dopamine. Although cell surface DAT trafficking recently emerged as an important component of DAT regulation, it has not been systematically investigated. Here, we apply our single quantum dot (Qdot) tracking approach to monitor DAT plasma membrane dynamics in several heterologous expression cell hosts with nanometer localization accuracy.

Real colloidal quantum dot structures revealed by high resolution analytical electron microscopy.

The development of bright and photostable colloidal quantum dots has been a truly interdisciplinary feat. Designing a specific composition of core and shell materials and then producing the desired nanoarchitecture through chemical routes require a blend of physical and inorganic chemistry, solid-state physics, and materials science. In a battle to separate charge carriers from a surface wrought with defect states, complex shell structures with precisely specified gradient compositions have been engineered, producing nanosized emitters with exceptional stability and color purity.

Biotinylated-spiperone ligands for quantum dot labeling of the dopamine D2 receptor in live cell cultures.

We have synthesized 3 analogs of the dopamine D2 receptor (D2 DR) antagonist spiperone that can be conjugated to streptavidin-coated quantum dots via a pegylated biotin derivative. Using fluorescent imaging we demonstrate that substitution on the spiro position is tolerated, whilst the length and rigidity of a spacer arm attached to spiperone is important in controlling specific labeling as well as minimizing nonspecific labeling to cells and the surface of cell culture dishes. The ligand with the most rigid linker IDT772 (4) had the best binding profile and had high specific binding to D2 DR expressing HEK-293T cells with low nonspecific binding to plates and HEK-293T cells that lacked the D2 DR.

Role of Surface Morphology on Exciton Recombination in Single Quantum Dot-in-Rods Revealed by Optical and Atomic Structure Correlation.

The physical structure of colloidal quantum dot (QD) nanostructures strongly influences their optical and electronic behavior. A fundamental understanding of this interplay between structure and function is crucial to fully tailor the performance of QDs and their assemblies. Here, by directly correlating the atomic and chemical structure of single CdSe-CdS quantum dot-in-rods with time-resolved fluorescence measurements on the same structures, we identify morphological irregularities at their surfaces that moderate photoluminescence efficiencies.

Nanotechnology in Neuroscience Reveals Membrane Mobility Matters.

Quantum dots are nanometer-sized semiconductors that have size-tunable, narrow emission bands, high quantum yields, and are resistant to photobleaching. Ligand-conjugated quantum dots enable the real time visualization of membrane proteins and have revealed that membrane diffusion dynamics are intrinsic to protein regulation, are susceptible to the level of membrane cholesterol, and are altered in genetic variants linked to disease, suggesting a mise en place approach to neuropsychopharmacology.

Single Quantum Dot Tracking Illuminates Neuroscience at the Nanoscale.

The use of nanometer-sized semiconductor crystals, known as quantum dots, allows us to directly observe individual biomolecular transactions through a fluorescence microscope. Here, we review the evolution of single quantum dot tracking over the past two decades, highlight key biophysical discoveries facilitated by quantum dots, briefly discuss biochemical and optical implementation strategies for a single quantum dot tracking experiment, and report recent accomplishments of our group at the interface of molecular neuroscience and nanoscience.