Method for Electrochemical Detection of Brain Derived Neurotrophic Factor (BDNF) in Plasma.

Currently, a blood test for the diagnosis of endometriosis, a common estrogen-dependent gynecological disease, does not exist. Recent studies suggest that circulating concentrations of brain-derived neurotrophic factor (BDNF) have potential for the diagnosis of endometriosis. However, at present, BDNF can only be measured by ELISA, which requires a clinic visit, a routine blood sample, and laboratory testing. Therefore, we developed a point-of-care device (EndoChip) for use with small blood volumes that can be collected through a finger prick. Specifically, the presented device is a polymer-based chip with a nanoporous, wrinkled gold film acting as the electrode/sensing layer, allowing for the electrochemical detection of BDNF in plasma. Increasing concentrations of BDNF (0.1-2.0 ng/mL) induced significant differences in redox current. The biosensor produces a signal readout in a matter of seconds, and is ideal for realizing multiplexing. Blood samples were collected from women ( n = 20) with chronic pelvic pain undergoing a diagnostic laparoscopy. Plasma BDNF concentrations measured by commercial ELISA were positively correlated ( r2 = 0.8033; p < 0.001) with results from the EndoChip. Our results demonstrate a quick and reliable method for point-of-care quantification of circulating concentrations of BDNF and a promising diagnostic tool for endometriosis.

Enrichment of magnetic particles using temperature and magnetic field gradients induced by benchtop fabricated micro-electromagnets.

The active transport of analytes inside biosensing systems is important for reducing the response time and enhancing the limit-of-detection of these systems. Due to the ease of functionalization with bio-recognition agents and manipulation with magnetic fields, magnetic particles are widely used for active and directed transport of biological analytes. On-chip active electromagnets are ideally suited for manipulating magnetic particles in an automated and miniaturized fashion inside biosensing systems. Unfortunately, the magnetic force exerted by these devices decays rapidly as we move away from the device edges, and increasing the generated force to the levels necessary for particle manipulation requires a parallel increase in the applied current and the resultant Joule heating. In this paper, we designed a study to understand the combined role of thermal and magnetic forces on the movement of magnetic particles in order to extend the interaction distance of on-chip magnetic devices beyond the device edges. For this purpose, we used a rapid prototyping method to create an active/passive on-chip electromagnet with a micro/nano-structured active layer and a patterned ferromagnetic passive layer. We demonstrated that the measured terminal velocities of particles positioned near the electromagnet edge (∼5.5 µm) closely reflect the values obtained by multi-physics modelling. Interestingly, we observed a two orders of magnitude deviation between the experimental and modelling results for the terminal velocities of particles far from the electromagnet edge (∼55.5 µm). Heat modelling of the system using experimentally-measured thermal gradients indicates that this discrepancy is related to the enhanced fluid movement caused by thermal forces. This study enables the rational design of thermo-magnetic systems for thermally driving and magnetically capturing particles that are positioned at distances tens to hundreds of microns away from the edges of on-chip magnetic devices.

Deposition, patterning, and utility of conductive materials for the rapid prototyping of chemical and bioanalytical devices.

Rapid prototyping is a critical step in the product development cycle of miniaturized chemical and bioanalytical devices, often categorized as lab-on-a-chip devices, biosensors, and micro-total analysis systems. While high throughput manufacturing methods are often preferred for large-volume production, rapid prototyping is necessary for demonstrating and predicting the performance of a device and performing field testing and validation before translating a product from research and development to large volume production. Choosing a specific rapid prototyping method involves considering device design requirements in terms of minimum feature sizes, mechanical stability, thermal and chemical resistance, and optical and electrical properties. A rapid prototyping method is then selected by making engineering trade-off decisions between the suitability of the method in meeting the design specifications and manufacturing metrics such as speed, cost, precision, and potential for scale up. In this review article, we review four categories of rapid prototyping methods that are applicable to developing miniaturized bioanalytical devices, single step, mask and deposit, mask and etch, and mask-free assembly, and we will focus on the trade-offs that need to be made when selecting a particular rapid prototyping method. The focus of the review article will be on the development of systems having a specific arrangement of conductive or semiconductive materials.

Rapid prototyping of microfluidic devices with integrated wrinkled gold micro-/nano textured electrodes for electrochemical analysis.

Fully-integrated electro-fluidic systems with micro-/nano-scale features have a wide range of applications in lab-on-a-chip systems used for biosensing, biological sample processing, and environmental monitoring. Rapid prototyping of application-specific electro-fluidic systems is envisioned to facilitate the testing, validation, and market translation of several lab-on-a-chip systems. Towards this goal, we developed a rapid prototyping process for creating wrinkled micro-/nano-textured electrodes on shrink memory polymers, fabricating microfluidics using molds patterned by a craft-cutter, and bonding electrical and fluidic circuitries using a PDMS partial curing method optimized for creating void-free bonds at the side walls and surfaces of tall (>5 µm) micro-/nano-textured wrinkled electrodes. The resulting electro-fluidic devices, featuring closely spaced high topography electrodes for electrochemical analysis, can withstand flow-rates and burst pressures larger than 25 mL min(-1) and 125 kPa, respectively. In addition, the fully-integrated electrochemical flow-cell developed here demonstrates excellent electrochemical behaviour, with negligible scan to scan variation for over 100 cyclic voltammetry scans, and expected redox signatures measured under various voltage scan rates and fluidic flow rates.

Femtosecond laser nanostructuring for femtosensitive DNA detection.

In this paper, a new concept to achieve improved probe-target recognition has been devised by introducing a novel class of DNA-functionalized three-dimensional (3D), stand-free, and nanostructured electrodes. The gold nanofibrous electrodes were created using MHZ ultrafast laser material processing in air at ambient conditions. The developed nanofibrous DNA biosensor was characterized by cyclic voltammetry with the use of ferrocyanide as an electrochemical redox indicator. Currently, electrochemical signal enhancement which is of great significance for improving the sensitivity in DNA detection remains a great challenge. Through, enhanced surface area-to-volume ratio and more efficient arrangement of probe molecules on nanofibrous electrodes, our newly developed electrode system overcomes some of the sensitivity challenges of the existing systems. This nanofiber-based system realizes femtomolar (fM) sensitivity toward complementary target DNA, and demonstrates a very wide dynamic range (from 1 fM to 1 nM).