Development of Low Cost Rapid Fabrication of Sharp Polymer Microneedles for In Vivo Glucose Biosensing Applications

Abstract

New approaches to enable more effective management of diabetes mellitus, such as continuous glucose monitoring are being developed both to prevent unstable episodes of hypo or hyper glycaemia and also to provide an improved user experience. One emerging approach to realize these requirements is to fabricate a minimally invasive transdermal sensor for the direct in vivo detection of glucose in the interstitial fluid. Microneedles -sharp, microscopic structures measuring less than 1 mm in length -have been previously employed to allow painless penetration of the stratum corneum for delivery of drugs and vaccines. In this work we present, ultra sharp gold coated polymer microneedle arrays (sub micron tip radii) which are fabricated using a low cost polymer replication approach. Critical dimensions of the microneedle arrays are characterized using a combination of optical and scanning electron microscopies. Fabricated microneedle devices are characterized by cyclic voltammetry to explore functionality. The voltammetric detection of glucose is performed using ferrocene monocarboxylic acid as an oxidising mediator in the presence of glucose oxidase. The biosensor can be applied to the quantification of glucose in the physiological range (2 -13.5 mM). The sensors demonstrate high selectivity towards glucose with negligible interference from other oxidizable species including uric acid, ascorbic acid, mannose, fructose, salicylic acid (Aspirin) and acetaminophen (Paracetamol). This demonstrates potential future use of these microneedle devices for in vivo glucose detection.

Electrochemical nanosensors: advances and applications

“…Normal blood glucose levels are between 4.2 and 6.4 mM 41 ; by achieving a detection limit significantly lower than these levels, it allows for the possibility of pain free glucose detection from other bodily fluids including saliva. [42][43][44] The sensitivity of these discrete electrodes has been attributed to radial diffusion of the mediator molecule to the electrode surface. This results in enhanced mass transport which, when combined with the enhanced heterogeneous electron transfer rates observed at nanoelectrodes, 45 is a distinct advantage over macro electrodes which exhibit limited currents due to planar diffusion.…”

Microneedle array sensors based on carbon nanoparticle composites: interfacial chemistry and electroanalytical properties

“…Microneedle (MN) patches have garnered extensive interest for the transdermal delivery of drugs and vaccines where the small dimensions of the needles penetrating the skin fail to trigger the dermal nerves and offer near painless injection [1][2][3]. A wide variety of approaches have been investigated in the design and construction of the microneedle masters but tend to revolve around the lithography/etching of resist layers on silicon wafers [4][5][6] or the CNC milling of metal blocks (typically aluminium [7][8][9][10]). Lim and colleagues have provided a critique of the approaches taken in microneedle [7,11], but, irrespective of the process taken to acquire the master, the replication workhorse templates are almost invariably produced using PDMS [4,7,8,10,12,13].…”

“…The ability to manipulate the material composition of the MN patch has obvious advantages for therapeutic delivery applications, but it has also been shown to enable the production of MN arrays for sensing applications. A number of approaches have been taken in the development of electrochemical MN sensors for transdermal glucose monitoring but most rely on the deposition of Au or Pt onto preformed MN arrays [4,6,8,14,15].…”

Differences in biocompatibility of microneedles from cyclic olefin polymers with human endothelial and epithelial skin cells

“…Microneedle‐based transdermal drug delivery is highly attractive due to its needle‐free nature and potential for self‐administration, with corresponding benefits in increased patient compliance, reduced clinical time, elimination of needle‐stick injuries, and sharps waste . Microneedle‐based devices have also shown significant potential in transdermal diagnostics: electrodes may be used to detect biopotential signals such as ECG or EEG without the use of electrolytic gels or skin preparation, functionalised for applications in electrochemical diagnostics, or used to withdraw fluids for biomarker analysis …”

“…[1][2][3][4] Microneedle-based devices have also shown significant potential in transdermal diagnostics 5 : electrodes may be used to detect biopotential signals such as ECG or EEG without the use of electrolytic gels or skin preparation, functionalised for applications in electrochemical diagnostics, or used to withdraw fluids for biomarker analysis. [6][7][8] A microneedle is a short, sharp, spike-like structure, generally less than 1 mm in length, and is often provided in arrays that may number anything up to several hundred per square centimeter and that can penetrate the epidermal layer of the skin. Although microneedles were originally fabricated using techniques borrowed from the semiconductor industry, injection molding has emerged as a viable alternative for their manufacture, especially as technical advances have facilitated the accurate reproduction of the microscale features associated with microneedles.…”