Generic Method of Preparing Multifunctional Fluorescent Nanoparticles Using Flash NanoPrecipitation

Abstract

There is increased demand for nanoparticles with a high fluorescence yield that have the desired excitation wavelength, surface functionalization, and particle size to act as biological probes. Here, a simple, rapid, and robust method, Flash NanoPrecipitation (FNP), to produce such fluorescent nanoparticles is described. This process involves encapsulation of a hydrophobic fluorophore with an amphiphilic biocompatible diblock copolymer in a kinetically frozen state. FNP is used to produce nanoparticles ranging from 30 to 800 nm with fluorescence emission peaks ranging from, but not limited to, 370 nm to 720 nm. Such fluorescent nanoparticles remain stable in aqueous solutions, and, in contrast to soluble dyes, show no photobleaching. Fluorophores and drugs are incorporated into a single nanoparticle, allowing for simultaneous drug delivery and biological imaging. In addition, functionalization of nanoparticle surfaces with disease‐specific ligands permits precise cell targeting. These features make FNP‐produced fluorescent nanoparticles highly desirable for various biological applications.

Controlled Nanoparticle Formation by Diffusion Limited Coalescence

“…To promote a faster and better controlled mixing, an impinging jets mixer, Fig. 1(b), has been employed in this case [4,7].Despite the simplicity of the experimental method, one still lacks a comprehensive theoretical model that allows us to predict how particle size depends on the materials and process parameters, in particular on concentration. Therefore in many practical situations investigators still resort to simple empirical correlations [8] or to statistical methods such as experimental design [6].…”

“…Size influences the circulating half lifetime and is crucial for selective cellular uptake: NPs between 50 and 200 nm in size are desired in passive cancer tumor targeting as they are too large to harm healthy cells but small enough to penetrate into the diseased ones. In brain imaging, fluorescent dye loaded particles of about 100 nm with biocompatible polymer coatings are used because they produce small, sharply defined injection sites and show no toxicity in vivo or in vitro [2][3][4].…”

“…To promote a faster and better controlled mixing, an impinging jets mixer, Fig. 1(b), has been employed in this case [4,7].…”

“…Size influences the circulating half lifetime and is crucial for selective cellular uptake: NPs between 50 and 200 nm in size are desired in passive cancer tumor targeting as they are too large to harm healthy cells but small enough to penetrate into the diseased ones. In brain imaging, fluorescent dye loaded particles of about 100 nm with biocompatible polymer coatings are used because they produce small, sharply defined injection sites and show no toxicity in vivo or in vitro [2][3][4].Although there are several methods for NP preparation, only few of them permit a high level of control on the particle size and the particle size distribution [2]. Often, a water insoluble moiety (e.g., a drug or a dye), needs to be encapsulated into a carrier polymer and protected by an emulsifying agent, which also makes the NP water soluble.…”

Whispering-gallery mode lasers for biosensing: a rationale for reducing the lasing threshold

“…This figure illustrates clearly that upon reaching the optimum dye concentration within the microsphere, the lasing threshold can be significantly reduced, in this case down to 2.4 μW. However, once the optimum dye concentration is reached, any subsequent increase in the dye content within the microsphere results in self-quenching of the organic dye [21] , and hence a higher lasing threshold.…”