Conductive polymer coatings can be used to modify traditional electrode recording sites with the intent of improving the long-term performance of cortical microelectrodes. Conductive polymers can drastically decrease recording site impedance, which in turn is hypothesized to reduce thermal noise and signal loss through shunt pathways. Moreover, conductive polymers can be seeded with agents aimed at promoting neural growth toward the recording sites or minimizing the inherent immune response. The end goal of these efforts is to generate an ideal long-term interface between the recording electrode and surrounding tissue. The goal of this study was to refine a method to electrochemically deposit surfactant-templated ordered poly(3,4-ethylenedioxythiophene) (PEDOT) films on the recording sites of standard 'Michigan' probes and to evaluate the efficacy of these modified sites in recording chronic neural activity. PEDOT-coated site performance was compared to control sites over a six-week evaluation period in terms of impedance spectroscopy, signal-to-noise ratio, number of viable unit potentials recorded and local field potential recordings. PEDOT sites were found to outperform control sites with respect to signal-to-noise ratio and number of viable unit potentials. The benefit of reduced initial impedance, however, was mitigated by the impedance contribution of typical silicon electrode encapsulation. Coating sites with PEDOT also reduced the amount of low-frequency drift evident in local field potential recordings. These findings indicate that electrode sites electrochemically deposited with PEDOT films are suitable for recording neural activity in vivo for extended periods. This study also provided a unique opportunity to monitor how neural recording characteristics develop over the six weeks following implantation.

Nanopores and submicrometer pores have recently been explored for applications ranging from detection of single molecules, assemblies of nanoparticles, nucleic acids, occurrence of chemical reactions, and unfolding of proteins. Most of these applications rely on monitoring electrical current through these pores, hence the noise and signal bandwidth of these current recordings are critical for achieving accurate and sensitive measurements. In this report, we present a detailed theoretical and experimental study on the noise and signal bandwidth of current recordings from glass and polyethylene terephthalate (PET) membranes that contain a single submicrometer pore or nanopore. We examined the theoretical signal bandwidth of two different pore geometries, and we measured the signal bandwidth of the electronics used to record the ionic current. We also investigated the theoretical noise generated by the substrate material, the pore, and the electronics used to record the current. Employing a combination of theory and experimental results, we were able to predict the noise in current traces recorded from glass and PET pores with no applied voltage with an error of less than 12% in a range of signal bandwidths from 1 to 40 kHz. In approximately half of all experiments, application of a voltage did not significantly increase the noise. In the other half of experiments, however, application of a voltage resulted in an additional source of noise. For these pores, predictions of the noise were usually still accurate within 35% error at signal bandwidths of at least 10 kHz. The power spectra of this extra noise suggested a 1/f(alpha) origin with best fits to the power spectrum for alpha = 0.4-0.8. This work provides the theoretical background and experimental data for understanding the bandwidth requirements and the main sources of noise in current recordings; it will be useful for minimizing noise and achieving accurate recordings.

A resistive‐pulse sensor (see scheme) employs a submicrometer pore for the detection, characterization, and quantification of the binding of polyclonal antibodies to intact Paramecium bursaria chlorella virus (PBCV‐1) particles. The assay is rapid, label‐free, requires no immobilization or modification of the antibody or virus, detects the formation of viral aggregates, and can be performed using antibodies in complex media such as serum. The maximum number of antibodies able to bind to the virus was estimated to be 4200±450.

We present herein a method that uses a submicrometer pore to detect and characterize immune complexes consisting of proteins such as staphylococcal enterotoxin B (an agent with bioterrorism potential) and polyclonal antibodies. The assay is rapid, label free, requires no immobilization or modification of the antibody or antigen, and achieves single-aggregate sensitivity by monitoring changes in electrical resistance when immune complexes pass through the submicrometer pore. Adopting a recently developed nanofabrication technique based on a femtosecond-pulsed laser made it possible to fabricate pores with conical geometries and diameters as small as 575 nm. These pores allowed sensing of immune complexes that consisted of 610-17 300 proteins and detection of proteins at concentrations as low as 30 nm. Monitoring the passage of individual immune complexes enabled determination of the size distribution and the growth of these complexes. This method senses immune complexes (and potentially other molecules or nanoparticles that can be induced to form specific assemblies) in solution, and the antibody or antigen to be detected can be present in complex media such as serum. Owing to the small footprint and simple detection scheme, submicrometer pore-based sensing of specific complexes may enable portable or high-throughput immunoassays for diagnostics and biodefense.Coulter counting, which monitors the transient change in resistance (resistive pulse) that occurs when a particle passes through a small pore filled with electrolyte, is a technique for detecting and analyzing micro-, and increasingly, nanoscale objects. As the sensitivity of a Coulter counter increases with decreasing pore diameter and length, [1] numerous techniques have been developed for the fabrication of single-nanopore [2][3][4][5][6][7][8][9][10] or nanotube membranes. [1,[11][12][13] Pore-forming proteins in planar lipid bilayers (PLBs) have been elegantly used as versatile nanopore sensors; [14][15][16][17][18][19][20] fabricated structures, in comparison, can offer a high degree of robustness and withstand environmental stress such as vibration, pressure, extreme pH, and elevated temperatures. Fabricated nanopores and nanotubes have been used for resistive-pulse sensing to detect viruses, [21] the aggregation of colloids, [22] DNA, [4,[7][8][9][10][11] nanoparticles, [1,13,23,24] and proteins. [12,25] The two reports of protein detection relied either on immobilized molecular-recognition agents on the walls of the nanopore [25] or on functionalized colloids. [12] We hypothesized that a specific protein could be detected rapidly, without the need for immobilization or labeling, by combining a submicrometer pore with Coulter counting to monitor the formation of immune complexes in solution.We adopted and optimized a recently developed nanomachining technique that employs femtosecond-pulsed lasers [26][27][28] to fabricate submicrometer pore structures in borosilicate glass coverslides (see Figure 1 and the Supporting Information). This technique has...

We present herein a method that uses a submicrometer pore to detect and characterize immune complexes consisting of proteins such as staphylococcal enterotoxin B (an agent with bioterrorism potential) and polyclonal antibodies. The assay is rapid, label free, requires no immobilization or modification of the antibody or antigen, and achieves single-aggregate sensitivity by monitoring changes in electrical resistance when immune complexes pass through the submicrometer pore. Adopting a recently developed nanofabrication technique based on a femtosecond-pulsed laser made it possible to fabricate pores with conical geometries and diameters as small as 575 nm. These pores allowed sensing of immune complexes that consisted of 610-17 300 proteins and detection of proteins at concentrations as low as 30 nm. Monitoring the passage of individual immune complexes enabled determination of the size distribution and the growth of these complexes. This method senses immune complexes (and potentially other molecules or nanoparticles that can be induced to form specific assemblies) in solution, and the antibody or antigen to be detected can be present in complex media such as serum. Owing to the small footprint and simple detection scheme, submicrometer pore-based sensing of specific complexes may enable portable or high-throughput immunoassays for diagnostics and biodefense.Coulter counting, which monitors the transient change in resistance (resistive pulse) that occurs when a particle passes through a small pore filled with electrolyte, is a technique for detecting and analyzing micro-, and increasingly, nanoscale objects. As the sensitivity of a Coulter counter increases with decreasing pore diameter and length, [1] numerous techniques have been developed for the fabrication of single-nanopore [2][3][4][5][6][7][8][9][10] or nanotube membranes. [1,[11][12][13] Pore-forming proteins in planar lipid bilayers (PLBs) have been elegantly used as versatile nanopore sensors; [14][15][16][17][18][19][20] fabricated structures, in comparison, can offer a high degree of robustness and withstand environmental stress such as vibration, pressure, extreme pH, and elevated temperatures. Fabricated nanopores and nanotubes have been used for resistive-pulse sensing to detect viruses, [21] the aggregation of colloids, [22] DNA, [4,[7][8][9][10][11] nanoparticles, [1,13,23,24] and proteins. [12,25] The two reports of protein detection relied either on immobilized molecular-recognition agents on the walls of the nanopore [25] or on functionalized colloids. [12] We hypothesized that a specific protein could be detected rapidly, without the need for immobilization or labeling, by combining a submicrometer pore with Coulter counting to monitor the formation of immune complexes in solution.We adopted and optimized a recently developed nanomachining technique that employs femtosecond-pulsed lasers [26][27][28] to fabricate submicrometer pore structures in borosilicate glass coverslides (see Figure 1 and the Supporting Information). This technique has...