Microscopic gel–liquid interfaces supported by hollow microneedle array for voltammetric drug detection

Abstract

This report describes a method for integration of a gel-liquid interface in hollow microneedles compatible with minimally invasive, electrochemical detection of drugs in vivo. The electrochemical sensor was characterised using cyclic voltammetry of tetraethyl ammonium. The experimental work demonstrated the detection of propranolol as a representative drug in physiological buffer with the microneedle system. A calibration curve for propranolol was built from measurements with differential pulse stripping voltammetry, indicating a sensitivity of 43 nA µM-1 , a limit of detection of 50 nM and a linear range between 50-200 nM.

An array of individually addressable micro-needles for mapping pH distributions

“…Buffer salts (pH 4,5,6,7,8), KCl, NaCl, KNO3, Na2HPO4, NaH2PO4, MgCl2, CaCl2, NaHCO3, glucose, K3IrCl6, K2CO3, oxalic acid, were from Sigma-Aldrich, UK. N2 (99.9%) and the mixture O2/CO2 (95/5) were from BOC, UK.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Silicon has been used predominantly for fabrication of microneedles, however the fragility and the cost of the microfabrication process are major drawbacks for this material. [1][2][3][4] Injection molding has instead emerged as an alternative fabrication process offering advantages such as cost and robustness.…”

Applications of Electrochemistry at Liquid/Liquid Interfaces for Ionizable Drug Molecule Sensing

“…Another new way to create ITIES is the use of a microneedle array with an embedded micro-ITIES platform for detecting propranolol. 20) Future designs featuring different ITIES configurations with specific functionality or purpose will definitely accelerate the ITIES research field for sensing applications including drug molecules.…”

“…Using DPSV, the microneedle based sensor showed a linear dynamic range between 50 -200 nM for propranolol with a limit of detection of 50 nM. 20) In addition to propranolol, other drug molecules including anticancer drugs have been studied; for instance, Pereira et al, 26) demonstrated that the transfer processes of the lipophilic anticancer drug daunorubicin (DNR) could be monitored across the large scale water/1,6-dichlorohexane (1,6-DCH) interface using differential pulse voltammetry (DPV). The lipophilicity studies of DNR at the ITIES were presented in the form of an ionic partition diagram and the partition coefficients of both neutral and ionic forms of the drug were determined.…”

Electrodeposited Iron as a Biocompatible Material for Microneedle Fabrication

“…vaccines), from the skin surface to deeper tissues,a nd have most recently been investigated for use in tissue suture and diagnostic applications [1][2][3].S olid, degradable,a nd hollow microneedles comprise the mainn eedle geometries used. Fors ensing applications,h ollow microneedles are preferred that can be integrated with am icrofluidic diagnostic chip [4,5], while diffusion-based analytec ollection methods have been shown to circumvent issues associated with extraction of interstitial fluid using hollow microneedles [6][7][8].Hollow microneedles allow for larger volumestobedelivered comparedt oc oated or degradable needles however specialc onsideration must be taken to prevent clogging after insertioni nto the skin [ 9].A no ffset bore allows for increased fluid delivery and improved fluid extraction [10,11].S everalf abrication techniques existt hat are capable of creating arrays of hollowm icroneedles with offset bores.I nitiale fforts concentrated on conventional silicon microfabricationt echniquesw hich still remain in common use [12].R ecently,alow cost approach that involvesacombination of UV lithography [a] Abstract:E lectroplated iron wasi nvestigated as an ovel material for microneedle fabrication due to its recent success as ab iocompatiblem etal in other medical devicea pplications.H ollow polymerm icroneedles were made using al aser direct write processt hat involvedt wophoton polymerization of ac ommercially available Class 2a biocompatible polymera nd subsequent electroplating of this structure with iron.E lectroplating bath and deposition conditions were shown to affect the mechanical properties of both iron plated microneedles and iron plated on planarp olymer substrates.C onditions for depositingt he iron coatings were investigatedi nt erms of grain size,r esidual strain, and elemental composition for planar iron samples.F racture strength and puncture mechanics into ex vivo porcine skin for ironc oated hollow microneedlesw ere examined. Biocompatibility testing wasp erformed usingt he MTT assay against human epidermal keratinocytesw ith several concentrations of iron extract to investigate iron as am aterial used for transdermal applications.I ron coatings proved to significantly improve the strength of the hollowp olymerm icroneedles and sustained structural integrityu pt o7i nsertions into porcine skin without bending.Acommercially available device (Medtronic MiniMedQ uick-Serter )w as used for controlled application of microneedles into porcines kin and estimations of insertion forces for the device were made.P lating conditionsw ere optimized such that an adherent, uniform,a nd high purity iron coating was deposited onto polymer substrates and polymerm icroneedles without delamination or fracturing of the microneedles upon ex vivo insertion into porcines kin.…”