NIR Luminescent Oxygen-Sensing Nanoparticles for Continuous Glucose and Lactate Monitoring

Abstract

A highly sensitive, biocompatible, and scalable phosphorescent oxygen sensor formulation is designed and evaluated for use in continuous metabolite sensors for biological systems. Ethyl cellulose (EC) and polystyrene (PS) nanoparticles (NPs) stabilized with Pluronic F68 (PF 68), Polydimethylsiloxane-b-polyethyleneglycol methyl ether (PDMS-PEG), sodium dodecylsulfate (SDS), and cetyltimethylammonium bromide (CTAB) were prepared and studied. The resulting NPs with eight different surfactant–polymer matrix combinations were evaluated for physical properties, oxygen sensitivity, effect of changes in dispersion matrix, and cytotoxicity. The EC NPs exhibited a narrower size distribution and 40% higher sensitivity than PS, with Stern–Volmer constants (Ksv) 0.041–0.052 µM−1 for EC, compared to 0.029–0.034 µM−1 for PS. Notably, ethyl cellulose NPs protected with PF68 were selected as the preferred formulation, as they were not cytotoxic towards 3T3 fibroblasts and exhibited a wide phosphorescence lifetime response of >211.1 µs over 258–0 µM and ~100 µs over 2.58–0 µM oxygen, with a limit of detection (LoD) of oxygen in aqueous phase of 0.0016 µM. The EC-PF68 NPs were then efficiently encapsulated in alginate microparticles along with glucose oxidase (GOx) and catalase (CAT) to form phosphorescent nanoparticles-in-microparticle (NIMs) glucose sensing microdomains. The fabricated glucose sensors showed a sensitivity of 0.40 µs dL mg−1 with a dynamic phosphorescence lifetime range of 46.6–197.1 µs over 0–150 mg dL−1 glucose, with a glucose LoD of 18.3 mg dL−1 and maximum distinguishable concentration of 111.1 mg dL−1. Similarly, lactate sensors were prepared with NIMs microdomains containing lactate oxidase (LOx) and found to have a detection range of 0–14 mg dL−1 with LoD of 1.8 mg dL−1 and maximum concentration of 13.7 mg dL−1 with lactate sensitivity of 10.7 µs dL mg−1. Owing to its versatility, the proposed NIMs-based design can be extended to a wide range of metabolites and different oxygen-sensing dyes with different excitation wavelengths based on specific application.

Continuous and Non-Invasive Lactate Monitoring Techniques in Critical Care Patients

“…Additionally, in an innovative and recent study by Jeevarathinam et al [ 34 ], it has been demonstrated that the combination of PDMS with polyethylene glycol (PEG) and ethyl cellulose (EC) nanoparticles enhances lactate sensors. Specifically, a highly sensitive and biocompatible phosphorescent oxygen sensor has been developed for continuous monitoring of lactate and glucose.…”

Long-Term Evaluation of Inserted Nanocomposite Hydrogel-Based Phosphorescent Oxygen Biosensors: Evolution of Local Tissue Oxygen Levels and Foreign Body Response

“…This effect improves the sensor's efficiency by ensuring that each phosphor consistently interacts with available oxygen. 23 2.3. Oxygen-Sensitive Microparticle Synthesis.…”

“…It also supports our previous findings from in vitro experiments, which showed that while apparent phosphorescence intensity depends on the intervening tissue, phosphorescence lifetime measurements are unaffected as long as the signal is strong enough to be reliably detected. 23,39 3.6. Detailed Discussion by Sensor Type.…”

“…Therefore, tissue oxygen sensors are of keen interest for treating peripheral artery disease, ischemia and reperfusion injury, microvascular disease in diabetics, and in monitoring wound healing . We have expanded this family of metal-porphyrin insertable sensors by developing new methods to encapsulate phosphor complexes in hydrogels that prevent phosphor aggregation, improve optical efficiency and sensitivity, and reduce the amount of metal-porphyrin complex required per sensor . In particular, the use of microsphere encapsulation also allows us to tightly control nutrient diffusion to the phosphor, providing an avenue toward insertable biosensors beyond oxygen, including glucose, lactate, or amino acid biosensors.…”

Research Progress on Biomimetic Nanomaterials for Electrochemical Glucose Sensors

“…The key core part in electrochemical sensors for accurate detection of glucose is the sensitive materials used for sensing glucose, including biological materials and biomimetic materials [ 22 , 23 ]. Biological materials mainly include glucose oxidase (GOx) or glucose dehydrogenases (GDHs) [ 24 , 25 ].…”