A new nucleic acid detection method was developed for a rapid and cost-effective diagnosis of infectious disease. This approach relies on the three unique elements: 1) detection probes that regulate DNA polymerase activity in response to the complementary target DNA; 2) universal reporters conjugated with a single fluorophore; and 3) fluorescence polarization (FP) detection. As a proof-of-concept, the assay was used to detect and sub-type Salmonella bacteria with sensitivities down to a single bacterium in less than three hours.

Platinum(II) compounds, principally cisplatin and carboplatin, are commonly used front-line cancer therapeutics. Despite their widespread use and continued interest in the development of new derivatives, including nanoformulations with improved properties, it has been difficult to visualize platinum compounds in live subjects, in real time, and with subcellular resolution. Here, we present four novel cisplatin- and carboplatin-derived fluorescent imaging compounds for quantitative intravital cancer imaging. We conjugated 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-daiza-s-indacene (BODIPY) to Pt^II complexes to generate derivatives with robust in vivo fluorescence and retained DNA-damaging and cytotoxic properties. We successfully applied these compounds to image pharmacokinetics and tumor uptake in a xenograft cancer mouse model. By using a genetic reporter of single-cell DNA damage for in vivo imaging, Pt drug accumulation and resultant DNA damage could be monitored in individual tumor cells, at subcellular resolution, and in real time in a live animal model of cancer. These derivatives represent promising imaging tools that will be useful in understanding further the distribution and interactions of platinum within tumors.

Fluorine-containing fluorochromes are important validation agents for positron emission tomography imaging compounds, as they can be readily validated in cells by fluorescence imaging. In particular, the ¹⁸F-labeled BODIPY-FL fluorophore has emerged as an important platform, but little is known about alternative ¹⁸F-labeling strategies or labeling on red-shifted fluorophores. In this study we explore acid-catalyzed ¹⁸F/¹⁹F exchange on a range of commercially available N-hydroxysuccinimidyl ester and maleimide BODIPY fluorophores. We show this method to be a simple and efficient ¹⁸F-labeling strategy for a diverse span of fluorescent compounds, including a BODIPY-modified PARP-1 inhibitor, and amine- and thiol-reactive BODIPY fluorophores.

We have developed a series of new ultrafluorogenic probes in the blue-green region of the visible-light spectrum that display fluorescence enhancement exceeding 11 000-fold. These fluorogenic dyes integrate a coumarin fluorochrome with the bioorthogonal trans-cyclooctene(TCO)–tetrazine chemistry platform. By exploiting highly efficient through-bond energy transfer (TBET), these probes exhibit the highest brightness enhancements reported for any bioorthogonal fluorogenic dyes. No-wash, fluorogenic imaging of diverse targets including cell-surface receptors in cancer cells, mitochondria, and the actin cytoskeleton is possible within seconds, with minimal background signal and no appreciable nonspecific binding, opening the possibility for in vivo sensing.

We have developed a series of new ultrafluorogenic probes in the blue-green region of the visible-light spectrum that display fluorescence enhancement exceeding 11 000-fold. These fluorogenic dyes integrate a coumarin fluorochrome with the bioorthogonal trans-cyclooctene(TCO)–tetrazine chemistry platform. By exploiting highly efficient through-bond energy transfer (TBET), these probes exhibit the highest brightness enhancements reported for any bioorthogonal fluorogenic dyes. No-wash, fluorogenic imaging of diverse targets including cell-surface receptors in cancer cells, mitochondria, and the actin cytoskeleton is possible within seconds, with minimal background signal and no appreciable nonspecific binding, opening the possibility for in vivo sensing.

Sensitive, rapid and phenotype-specific enumeration of pathogens is essential for the diagnosis of infectious disease, monitoring of food chains, and for defense against bioterrorism. Microbiological culture and genotyping, techniques that sensitively and selectively detect bacteria in laboratory settings, have limited application in clinical environments due to high cost, slow response times, and the need for specially trained staff and laboratory infrastructure. To address these challenges, we developed a microfluidic chip-based micro-Hall (μHall) platform capable of measuring single, magnetically tagged bacteria directly in clinical specimens with minimal sample processing. We demonstrated the clinical utility of the μHall chip by enumerating Gram-positive bacteria. The overall detection limit of the system was similar to that of culture tests (∼10 bacteria), but the assay time was 50-times faster. This low-cost, single-cell analytical technique is especially well-suited to diagnose infectious diseases in resource-limited clinical settings.

A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with ¹⁸F-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging.