LipiSensors: Exploiting Lipid Nanoemulsions to Fabricate Ionophore-Based Nanosensors

Abstract

Ionophore-based nanosensors (IBNS) are tools that enable quantification of analytes in complex chemical and biological systems. IBNS methodology is adopted from that of bulk optodes where an ion exchange event is converted to a change in optical output. While valuable, an important aspect for application is the ability to intentionally tune their size with simple approaches, and ensure that they contain compounds safe for application. Lipidots are a platform of size tunable lipid nanoemulsions with a hydrophobic lipid core typically used for imaging and drug delivery. Here, we present LipiSensors as size tunable IBNS by exploiting the Lipidot model as a hydrophobic structural support for the sensing moieties that are traditionally encased in plasticized PVC nanoparticles. The LipiSensors we demonstrate here are sensitive and selective for calcium, reversible, and have a lifetime of approximately one week. By changing the calcium sensing components inside the hydrophobic core of the LipiSensors to those sensitive for oxygen, they are also able to be used as ratiometric O2 sensitive nanosensors via a quenching-based mechanism. LipiSensors provide a versatile, general platform nanosensing with the ability to directly tune the size of the sensors while including biocompatible materials as the structural support by merging sensing approaches with the Lipidot platform.

Sensors in a Flash! Oxygen Nanosensors for Microbial Metabolic Monitoring Synthesized by Flash Nanoprecipitation

“…However, this change in material properties is not a concern for the sensing mechanism, as other work has already demonstrated that for this class of sensors, the structural nanoparticle matrix is easily adaptable to other materials assuming the hydrophobicity remains similar, a result extended in this work. 14 , 18 , 39 …”

“… 16 However, the current fabrication approach for nanosensors is reliant on emulsification solvent evaporation (ESE)—yielding minimal nanoparticle size control, large polydispersity, and poor options to select specific nanoparticle sizes while retaining sensor function. 17 While some alternate approaches with different materials have shown some limited size tuning, 18 the current approaches do not offer the control over nanoparticle fabrication seen with FNP.…”

Ionophore-Based Potassium Selective Fluorescent Organosilica Nano-Optodes Containing Covalently Attached Solvatochromic Dyes

“…Ionophore-based ionselective electrodes and optodes have been widely recognized because of the high selectivity, versatility, and robustness [8][9][10][11][12][13]. Recently, several research groups are interested in developing the nanoscale ion-selective optodes in the form of various nanoparticles [11,[14][15][16][17][18]. The nano-optodes could share a similar sensing mechanism with polymer film-based bulk optodes where an increase of K + concentration ([K + ]) leads to the deprotonation of a pH indicator (H + chromoionophore) in the nanospheres [19][20][21].…”

Cubosome Based Ion-Selective Optodes–Toward Tunable Biocompatible Sensors

“…19 Moreover, stable in solution cubosomes/hexosomes are obtained in a simple process. Surprisingly, lipid nanostructures were not of interest as ion-selective sensor matrices before 20,21 although biosensing with these systems has been considered. 22 From the point of view of ion-sensing, the additional advantage has the possibility of adjusting the internal arrangement of channels by a temperature trigger, affecting accessibility of the bulk probe for the analyte and ultimately controlling the response pattern of the sensor.…”

“…Moreover, stable in solution cubosomes/hexosomes are obtained in a simple process. Surprisingly, lipid nanostructures were not of interest as ion-selective sensor matrices before , although biosensing with these systems has been considered …”