Synthesis and Evaluation of GdIII‐Based Magnetic Resonance Contrast Agents for Molecular Imaging of Prostate‐Specific Membrane Antigen

Magnetic resonance (MR) imaging is advantageous because it concurrently provides anatomic, functional, and molecular information. MR molecular imaging can combine the high spatial resolution of this established clinical modality with molecular profiling in vivo. However, as a result of the intrinsically low sensitivity of MR imaging, high local concentrations of biological targets are required to generate discernable MR contrast. We hypothesize that the prostate‐specific membrane antigen (PSMA), an attractive target for imaging and therapy of prostate cancer, could serve as a suitable biomarker for MR‐based molecular imaging. We have synthesized three new high‐affinity, low‐molecular‐weight Gd^III‐based PSMA‐targeted contrast agents containing one to three Gd^III chelates per molecule. We evaluated the relaxometric properties of these agents in solution, in prostate cancer cells, and in an in vivo experimental model to demonstrate the feasibility of PSMA‐based MR molecular imaging.     

Rare Earth Ion Mediated Fluorescence Accumulation on a Single Microbead: An Ultrasensitive Strategy for the Detection of Protein Kinase Activity at the Single‐Cell Level

A single microbead‐based fluorescence imaging (SBFI) strategy that enables detection of protein kinase activity from single cell lysates is reported. We systematically investigated the ability of various rare earth (RE) ions, immobilized on the microbead, for specific capturing of kinase‐induced phosphopeptides, and Dy³⁺ was found to be the most prominent one. Through the efficient concentration of kinase‐induced fluorescent phosphopeptides on a Dy³⁺‐functionalized single microbead, kinase activity can be detected and quantified by reading the fluorescence on the microbead with a confocal fluorescence microscope. Owing to the extremely specific recognition of Dy³⁺ towards phosphopeptides and the highly‐concentrated fluorescence accumulation on only one microbead, ultrahigh sensitivity has been achieved for the SBFI strategy which allows direct kinase analysis at the single‐cell level.     

High‐contrast Noninvasive Imaging of Kidney Clearance Kinetics Enabled by Renal Clearable Nanofluorophores

Noninvasive imaging of kidney clearance kinetics (KCK) of renal clearable probes is key to studying unilateral kidney function diseases, but such imaging is highly challenging to achieve with in vivo fluorescence. While this long‐standing challenge is often attributed to the limited light penetration depth, we found that rapid and persistent accumulation of conventional dyes in the skin “shadowed” real fluorescence signals from the kidneys and prevented noninvasive imaging of KCK, which, however, can be addressed with renal clearable nanofluorophores. By integrating near infrared emission with efficient renal clearance and ultralow background interference, the nanofluorophores can increase kidney‐contrast enhancement and imaging‐time window by approximately 50‐ and 1000‐fold over conventional dyes, and significantly minimize deviation between noninvasive and invasive KCK, laying down a foundation for translating in vivo fluorescence imaging in preclinical noninvasive kidney function assessments.     

Interactions of DNA with graphene and sensing applications of graphene field-effect transistor devices: A review

Graphene field-effect transistors (GFET) have emerged as powerful detection platforms enabled by the advent of chemical vapor deposition (CVD) production of the unique atomically thin 2D material on a large scale. DNA aptamers, short target-specific oligonucleotides, are excellent sensor moieties for GFETs due to their strong affinity to graphene, relatively short chain-length, selectivity, and a high degree of analyte variability. However, the interaction between DNA and graphene is not fully understood, leading to questions about the structure of surface-bound DNA, including the morphology of DNA nanostructures and the nature of the electronic response seen from analyte binding. This review critically evaluates recent insights into the nature of the DNA graphene interaction and its affect on sensor viability for DNA, small molecules, and proteins with respect to previously established sensing methods. We first discuss the sorption of DNA to graphene to introduce the interactions and forces acting in DNA based GFET devices and how these forces can potentially affect the performance of increasingly popular DNA aptamers and even future DNA nanostructures as sensor substrates. Next, we discuss the novel use of GFETs to detect DNA and the underlying electronic phenomena that are typically used as benchmarks for characterizing the analyte response of these devices. Finally, we address the use of DNA aptamers to increase the selectivity of GFET sensors for small molecules and proteins and compare them with other, state of the art, detection methods.     

Detection of explosives on the surface of banknotes by Raman hyperspectral imaging and independent component analysis

The aim of this study was to develop a methodology using Raman hyperspectral imaging and chemometric methods for identification of pre- and post-blast explosive residues on banknote surfaces. The explosives studied were of military, commercial and propellant uses. After the acquisition of the hyperspectral imaging, independent component analysis (ICA) was applied to extract the pure spectra and the distribution of the corresponding image constituents. The performance of the methodology was evaluated by the explained variance and the lack of fit of the models, by comparing the ICA recovered spectra with the reference spectra using correlation coefficients and by the presence of rotational ambiguity in the ICA solutions. The methodology was applied to forensic samples to solve an automated teller machine explosion case. Independent component analysis proved to be a suitable method of resolving curves, achieving equivalent performance with the multivariate curve resolution with alternating least squares (MCR-ALS) method. At low concentrations, MCR-ALS presents some limitations, as it did not provide the correct solution. The detection limit of the methodology presented in this study was 50 μg cm⁻².     

An effective colorimetric and ratiometric fluorescent probe for bisulfite in aqueous solution

We have developed the first two-photon colorimetric and ratiometric fluorescent probe, BICO, for the detection of bisulfite (HSO₃⁻) in aqueous solution. The probe contains coumarin and benzimidazole moieties and can detect HSO₃⁻ based on the Michael addition reaction with a limit of detection 5.3 × 10⁻⁸ M in phosphate-buffered saline solution. The probe was used to detect bisulfite in tap water, sugar and dry white wine. Moreover, test strips were made and used easily. We successfully applied the probe to image living cells, using one-photon fluorescence imaging. BICO overcomes the limitations in sensitivity of previously reported probes and the solvation effect of bisulfite, which demonstrates its excellent value in practical application.