The direct visualization of neurotransmitters is a continuing problem in neuroscience; however, functional fluorescent sensors for organic analytes are still rare. Herein, we describe a fluorescent sensor for glutamate and zinc ions. The sensor acts as a fluorescent logic gate, giving a turn-off response to glutamate or zinc ion alone. The combination of analytes produces a large increase in fluorescence. This type of sensor will aid in the study of neurotransmission, in this case, for neurons that copackage high concentrations of zinc and glutamate.

Measurement of blood analytes provides crucial information about a patient's health. Some such analytes, such as glucose in the case of diabetes, require long-term or near-continuous monitoring for proper disease management. However, current monitoring techniques are far from ideal: multiple-per-day finger stick tests are inconvenient and painful for the patient; implantable sensors have short functional life spans (i.e., 3-7 days). Due to analyte transporters on red blood cell (RBC) membranes that equilibrate intracellular and extracellular analyte levels, RBCs serve as an attractive alternative for encapsulating analyte sensors. Once reintroduced to the blood stream, the functionalized RBCs may continue to live for the remainder of their life span (120 days for humans). They are biodegradable and biocompatible, thereby eliminating the immune system response common for many implanted devices. The proposed sensing system utilizes the ability of the RBCs to swell in response to a decrease in the osmolarity of the extracellular solution. Just before lysis, they develop small pores on the scale of tens of nanometers. While at low temperature, analyte-sensitive dyes in the extracellular solution diffuse into the perforated RBCs and become entrapped upon restoration of temperature and osmolarity. Since the fluorescent signal from the entrapped dye reports on changes in the analyte level of the extracellular solution via the RBC transporters, interactions between the RBCs and the dye are critical to the efficacy of this technique. In this work, we study the use of a near infrared pH sensitive dye encapsulated within RBCs and assess the ability to measure dye fluorescence in vivo.

In an effort to design near-infrared (NIR), water soluble glucose sensors, several pH sensitive NIR cyanine derivates were designed and synthesized to provide insight into the viability of the cyanine platform as the fluorophore core for performing minimally invasive long term glucose monitoring in vivo. Many previous efforts to build effective fluorescent sensors for glucose have provided guidance towards the architecture of binding groups and fluorescent response required to achieve this goal, but have not provided appropriate solubility, or excitation and emission characteristics for in vivo sensing. In an effort to address the aqueous solubility of the highly rigid cyanine platform, a tetra sulfonated core was chosen for this work. Though fully water soluble, pH sensitive derivates still showed some aggregation characteristics. Simple sugarbinding boronic acid derivatives showed appropriate fluorescent responses, but poor binding. Efforts to improve binding through synthesis of bis-boronic acid compounds proved elusive.

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