Enzymatic Fluorescent Microsphere Glucose Sensors:Evaluation of Response Under Dynamic Conditions

Abstract

Most previous attempts at the development of a "smart tattoo" for glucose monitoring in diabetes -implantable fluorescent microspheres that can be implanted intradermally and interrogated transdermally using light-have focused on the encapsulation of a competitive binding assay for glucose within hydrogel microspheres or polyelectrolyte microcapsules. We recently reported on the development of a microsphere sensor based on an enzymatic scheme, combined with an oxygen-quenched fluorescent reporter element. A novel feature of this design is the use of polyelectrolyte multilayer nanofilms, which are assembled stepwise on the surface of the microspheres, for modulation of glucose and oxygen mass transport, allowing them to be designed for sensitive and safe operation within the "oxygen deficit" present in the skin. In this work, a flow-through sensor testing apparatus was used to demonstrate the reversible response of the sensors under controlled, dynamic conditions. The sensors were shown to be sensitive over at least 0-140 mg/dL glucose, with a response time of less than 2 min. This report also identifies some current problems with the approach, and gives potential solutions towards the development of a practical implantable sensor for glucose monitoring in diabetes.

Enhancing the longevity of microparticle-based glucose sensors towards 1 month continuous operation

“…We have recently reported one possibility for this in the form of enzymatic luminescent microspheres (Brown and McShane 2006; Brown et al 2006; McShane et al 2006; Stein et al 2007; Stein et al 2008). These systems employ a phosphorescent indicator to transduce oxygen, which is consumed in proportion to the glucose level in the reaction with glucose oxidase (GOx), to luminescence intensity or lifetime.…”

Dissolved core alginate microspheres as “smart-tattoo” glucose sensors

“…Diabetes, with its high prevalence and mortality rate, ranks among the world’s deadliest diseases. Therefore, non-invasive or minimally invasive optical sensors also known as “smart tattoos” [1]–[14] intended for injection directly into the dermis [15]–[17] may prove to be an attractive alternative to established methods. Such implants may be interrogated non-invasively using simple optical instrumentation [4], [18] making their use all the more attractive.…”

Role of porosity in tuning the response range of microsphere-based glucose sensors

“…Luminescent microsphere-based glucose sensors have been proposed and studied for prospective use in minimally-invasive continuous glucose monitoring—as so-called “smart tattoo” materials (Brown and McShane 2006; Brown et al 2006; McShane 2002; Singh and McShane 2010; Stein et al 2007; Stein et al 2008). The goal of this sensing strategy is to implant the microbeads in the highly-vascularized dermis, where they can be optically interrogated with high efficiency, and the emission measurements (intensity or lifetime) may be used to predict interstitial glucose concentrations.…”