Nanoparticle biosensor for noninvasive glucose sensing

Fueled by the worldwide rise in obesity, diabetes is becoming a global public health crisis with nearly one in 10 people afflicted with the disease, according to World Health Organization statistics.¹ Currently, patients use finger-stick blood glucose sensors typically 4 to 6 times a day to strictly monitor their blood glucose levels (BGLs) in order to regulate their dosage of insulin or diabetes medication. This monitoring method is quite arduous to the diabetic patient, requiring hand washing, a finger prick with a lancet, and blood application to a test strip area. This is often times painful, publicly embarrassing, and costly to the patient.

The result is that many diabetic patients neglect blood glucose monitoring, despite serious complications that arise with prolonged elevated blood glucose levels. Thus, alternative methods to painful finger-prick glucose measurements are needed, such as monitoring BGLs via saliva or tear fluid. Measuring glucose in bodily secretions other than blood is challenging because glucose concentrations are often orders of magnitude lower than those found in blood, and the correlation between BGLs and glucose levels in other fluids (such as saliva) can vary according to the time they are monitored.²

Nanotechnology is opening the door to non-invasive glucose monitoring by increasing both the sensitivity and sensing range of electrochemical-based glucose monitors, the type of biosensor patients currently use to measure BGLs. Nanostructured biosensors can work on the same basis as conventional finger-prick-based biosensors, that is, an enzyme like glucose oxidase immobilized on an electrode breaks down glucose within the sample fluid to produce an electroactive species such as hydrogen peroxide that subsequently oxidizes on the electrode surface and generates electrons. These electrons are monitored on a digital readout and are correlated to glucose concentration. Such electrochemical biosensors have not been able to monitor glucose concentrations levels both in blood and saliva or tear fluid.

Our approach to improve nanostructured biosensor performance first used carbon nanotubes (CNTs) or porous anodic alumina for subsequent metallic nanoparticle and enzyme immobilization.^3–7 In these projects we were able to show how carbon nanotubes that were grown vertically from a silicon chip could be used as a highly conductive support for a wide range of nanoparticles, including palladium nanocubes,³ gold-coated palladium nanocubes³ and platinum nanospheres (see Figure 1, left).^3,5,6 In terms of electrochemical glucose sensing, biosensors enhanced with horizontal CNTs peppered with platinum nanoparticles were more sensitive than their palladium and gold nanoparticle counterparts. Furthermore, the spacing of the nanoparticles on the CNTs significantly impacted the biosensor performance as glucose diffusion is blocked when nanoparticles are too closely packed.⁵

Figure 1. Electrochemical glucose biosensors nanostructured with platinum (Pt) nanospheres on (left) carbon nanotubes and (right) graphene petals. (Reprinted with permission from Claussen et al. 2011, J. Phys. Chem. C, copyright 2011 from the American Chemical Society andClaussen et al. 2012, copyright 2012 from Wiley-VCH).

To prevent diffusion restrictions from neighboring nanoparticles and to increase the overall number of platinum nanoparticles on the biosensor surface, we grew a 3D architecture of multi-layered graphene petals on a silicon chip to improve the biosensor performance (see Figure 1, right). By incorporating layers of graphene peppered with nanosized platinum particles into the biosensor design, we showed that glucose detection in concentrations typically found in saliva, tears, blood, and urine can be monitored on the same biosensor chip, a feat we believe has not been demonstrated before.⁸

The concomitance of high surface area and catalytic properties of the 3D graphene/platinum nanoparticle hybrid structure enhances the glucose sensitivity and sensing range above and beyond that of conventional and nanostructured electrochemical biosensors, allowing for glucose sampling in bodily fluids other than blood. Moving forward, we aim to take this technology into clinical trials with actual biological samples so that glucose concentrations found in fluids such as saliva or tears can be properly assessed and compared to glucose found in blood samples. Such technology could provide the breakthrough needed to monitor BGLs through saliva or tears and eliminate the need for the painful finger prick.