CDy6, a photostable probe for long-term real-time visualization of mitosis and proliferating cells.

Long-term real-time visualization of lysosomal dynamics has been challenging at the onset of mitosis due to the lack of fluorescent probes enabling convenient imaging of dividing cells. We developed a long-term real-time photostable mitotic or proliferating marker, CDy6, a BODIPY-derived compound of designation yellow 6, which labels lysosome. In long-term real-time, CDy6 displayed a sharp increase in intensity and change in localization in mitosis, improved photostability, and decreased toxicity compared with other widely used lysosomal and DNA markers, and the ability to label cells in mouse xenograft models.

A molecular fluorescent probe for targeted visualization of temperature at the endoplasmic reticulum.

The dynamics of cellular heat production and propagation remains elusive at a subcellular level. Here we report the first small molecule fluorescent thermometer selectively targeting the endoplasmic reticulum (ER thermo yellow), with the highest sensitivity reported so far (3.9%/°C).

The role of "disaggregation" in optical probe development.

"Aggregation-caused signal change" is a well-established mechanism by now and has been widely used as the basis for optical probe and sensor development. Compared to aggregation, its reverse process, disaggregation, has received much less attention and is not properly discussed in the literature so far. With the less established paradigm or mechanism, although some of the reported sensors and probes seem to work through disaggregation phenomena, the proper interpretation of the results and applying the concept to novel probe development is seriously hampered.

Development of a fluorescent sensor for illicit date rape drug GHB.

The first fluorescent sensor (GHB Orange) for date rape drug GHB was developed. It exhibits the fluorescence quenching property for GHB and allows its detection in various drinks. The interaction mechanism was elucidated as intramolecular charge transfer induced by a hydrogen bond.

Neural stem cell isolation from the whole mouse brain using the novel FABP7-binding fluorescent dye, CDr3.

Methods for the isolation of live neural stem cells from the brain are limited due to the lack of well-defined cell surface markers and tools to detect intracellular markers. To date most methods depend on the labeling of extracellular markers using antibodies, with intracellular markers remaining inaccessible in live cells. Using a novel intracellular protein FABP7 (Fatty Acid Binding Protein-7) selective fluorescent chemical probe CDr3, we have successfully isolated high FABP7 expressing cells from the embryonic and adult mouse brains.

Fluorescent dye cocktail for multiplex drug-site mapping on human serum albumin.

Elucidating how molecules bind to HSA is fundamental for predicting drug incompatibilities. Through combinatorial screening, we identified a novel fluorescent dye (BD140) with turn-on fluorescence emission and specific binding at HSA drug site 2. We further combined it with dansylamide to develop a fluorescent dye cocktail for high-throughput mapping of the interaction between therapeutics at HSA drug-binding sites.

Make caffeine visible: a fluorescent caffeine "traffic light" detector.

Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. However, to detect it sensitively and conveniently remains a challenge, especially in resource-limited regions. Here we report a novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which exhibits 250-fold fluorescence enhancement upon caffeine activation and high selectivity.

A ratiometric fluorescent dye for the detection of glutathione in live cells and liver cancer tissue.

A novel ratiometric biothiol probe Glutathione Green was developed. It allows quantitative measurement of glutathione in cell extracts and direct visualization of changes in glutathione levels in live cells. Remarkably, this is the first reported biothiol probe which can detect the carcinoma region of liver tissue based on the differences in the glutathione level.

Development of a fluorescent sensor for an illicit date rape drug--GBL.

The first fluorescent sensor for an illicit date rape drug, GBL, was developed and named Green Date. It shows high fluorescence enhancement to GBL and allows its detection in different drinks. The mechanism between GBL and Green Date was explored.

The Development of Novel Near-Infrared (NIR) Tetraarylazadipyrromethene Fluorescent Dyes.

Novel structures of an near-infrared (NIR) tetraarylazadipyrromethene (aza-BODIPY) series have been prepared. We designed the core structure containing two amido groups at the para-position of the aromatic rings. The amido group was incorporated to secure insensitivity to pH and to ensure a bathochromic shift to the NIR region.

Neural stem cell specific fluorescent chemical probe binding to FABP7.

Fluorescent small molecules have become indispensable tools for biomedical research along with the rapidly developing optical imaging technology. We report here a neural stem cell specific boron-dipyrromethane (BODIPY) derivative compound of designation red 3 (CDr3), developed through a high throughput/content screening of in-house generated diversity oriented fluorescence library in stem cells at different developmental stages. This novel compound specifically detects living neural stem cells of both human and mouse origin.

Synthesis of a novel BODIPY library and its application in the discovery of a fructose sensor.

We prepared a new library of 160 compounds by conjugation of a BODIPY core to a collection of aldehydes. This library was screened against 52 biologically relevant analytes and we identified one fluorescent sensor of fructose (Fructose Orange). Fructose Orange showed a 24-fold fluorescence increase upon recognition of fructose and an outstanding selectivity among 24 different saccharides.

Solid-phase synthesis of BODIPY dyes and development of an immunoglobulin fluorescent sensor.

The diversification of the BODIPY scaffold has been hindered by its controversial adaptability to solid-phase chemistry. Herein we report the first solid-phase synthesis of a BODIPY library in high purities. We screened the library against a set of proteins, identified an immunoglobulin fluorescent sensor (Ig Orange) and confirmed its binding by SPR experiments.

Bodipy-diacrylate imaging probes for targeted proteins inside live cells.

A bodipy probe was developed for site-specific labeling of tagged proteins inside live cells which displays a large spectral change upon covalent coupling to the designed peptide that contains two pairs of Arg-Cys.