Mohamad Hajj-Hassan

NeuroMEMS: Neural Probe Microtechnologies

Neural probe technologies have already had a significant positive effect on our understanding of the brain by revealing the functioning of networks of biological neurons. Probes are implanted in different areas of the brain to record and/or stimulate specific sites in the brain. Neural probes are currently used in many clinical settings for diagnosis of brain diseases such as seizers, epilepsy, migraine, Alzheimers, and dementia. We find these devices assisting paralyzed patients by allowing them to operate computers or robots using their neural activity. In recent years, probe technologies were assisted by rapid advancements in microfabrication and microelectronic technologies and thus are enabling highly functional and robust neural probes which are opening new and exciting avenues in neural sciences and brain machine interfaces. With a wide variety of probes that have been designed, fabricated, and tested to date, this review aims to provide an overview of the advances and recent progress in the microfabrication techniques of neural probes. In addition, we aim to highlight the challenges faced in developing and implementing ultra-long multi-site recording probes that are needed to monitor neural activity from deeper regions in the brain. Finally, we review techniques that can improve the biocompatibility of the neural probes to minimize the immune response and encourage neural growth around the electrodes for long term implantation studies.

Direct-Dispense Polymeric Waveguides Platform for Optical Chemical Sensors

We describe an automated robotic technique called direct-dispense to fabricate a polymeric platform that supports optical sensor arrays. Direct-dispense, which is a type of the emerging direct-write microfabrication techniques, uses fugitive organic inks in combination with cross-linkable polymers to create microfluidic channels and other microstructures. Specifically, we describe an application of direct-dispensing to develop optical biochemical sensors by fabricating planar ridge waveguides that support sol-gel-derived xerogel-based thin films. The xerogel-based sensor materials act as host media to house luminophore biochemical recognition elements. As a prototype implementation, we demonstrate gaseous oxygen (O2) responsive optical sensors that operate on the basis of monitoring luminescence intensity signals. The optical sensor employs a Light Emitting Diode (LED) excitation source and a standard silicon photodiode as the detector. The sensor operates over the full scale (0%-100%) of O2 concentrations with a response time of less than 1 second. This work has implications for the development of miniaturized multi-sensor platforms that can be cost-effectively and reliably mass-produced.

Porous silicon and porous polymer substrates for optical chemical sensors

Mesoporous materials, such as porous silicon and porous polymer gratings (Bragg structures), offer an attractive platform for the encapsulation of chemical and biological recognition elements. These materials include the advantages of high surface to volume ratio, biocompatibility, functionality with various recognition elements, and the ability to modify the material surface/volume properties and porosity. Two porous structures were used for chemical and biological sensing: porous silicon and porous polymer photonic bandgap structures. Specifically, a new dry etching manufacturing technique employing xenon difluoride (XeF2) based etching was used to produce porous silicon Porous silicon continues to be extensively researched for various optical and electronic devices and applications in chemical and biological sensing are abundant. The dry etching technique to manufacture porous silicon offers a simple and efficient alternative to the traditional wet electrochemical etching using hydrofluoric acid. This new porous silicon material was characterized for its pore size and morphology using top and cross-sectional views from scanning electron microscopy. Its optical properties were determined by angular dependence of reflectance measurements. A new class of holographically ordered porous polymer gratings that are an extension of holographic polymer dispersed liquid crystal (H-PDLC) structures. As an alternative structure and fabrication process, porous polymer gratings that include a volatile solvent as the phase separation fluid was fabricated. Porous silicon and porous polymer materials were used as substrates to encapsulate gaseous oxygen (O2) responsive luminophores in their nanostructured pores. These substrate materials behave as optical interference filters that allow efficient and selective detection of the wavelengths of interest in optical sensors.

Reinforced silicon neural microelectrode array fabricated using a commercial MEMS process

We report the development of a silicon microelectrode array for brain machine interfaces and neural prosthesis fabricated in a com- mercial microelectromechanical systems MEMS process. We demon- strate high-aspect ratio silicon microelectrodes that reach 6.5 mm in length while having only 10 m thickness. The fabrication of such elon- gated neural microelectrodes could lead to the development of cognitive neural prosthetics. Cognitive neural signals are higher level signals that contain information related to the goal of movements such as reaching and grasping and can be recorded from deeper regions of the brain such as the parietal reach region PRR. We propose a new concept of rein- forcing the regions of the electrodes that are more susceptible to break- age to withstand the insertion axial forces, retraction forces, and tension forces of the brain tissue during surgical implantation. We describe the design techniques, detailed analytical models, and simulations to de- velop reinforced silicon-based elongated neural electrodes. The elec- trodes are fabricated using the commercial MicraGem process from Mi- cralyne, Inc. The use of a commercial MEMS fabrication process for silicon neural microelectrodes development yields low-cost, mass- producible, and well-defined electrode structures.

Controlling optical properties and surface morphology of dry etched porous silicon

This PDF file contains the errata for “JNP Vol. 5 Issue 01 Paper 3592487” for JNP Vol. 5 Issue 01

Response of murine bone marrow-derived mesenchymal stromal cells to dry-etched porous silicon scaffolds†

Porous silicon shows great promise as a bio-interface material due to its large surface to volume ratio, its stability in aqueous solutions and to the ability to precisely regulate its pore characteristics. In the current study, porous silicon scaffolds were fabricated from single crystalline silicon wafers by a novel xenon difluoride dry etching technique. This simplified dry etch fabrication process allows selective formation of porous silicon using a standard photoresist as mask material and eliminates the post-formation drying step typically required for the wet etching techniques, thereby reducing the risk of damaging the newly formed porous silicon. The porous silicon scaffolds supported the growth of primary cultures of bone marrow derived mesenchymal stromal cells (MSC) plated at high density for up to 21 days in culture with no significant loss of viability, assessed using Alamar Blue. Scanning electron micrographs confirmed a dense lawn of cells at 9 days of culture and the presence of MSC within the pores of the porous silicon scaffolds.

CMOS capactive sensor system for bacteria detection using phage organisms

The paper presents the design and implementation of a complementary metal-oxide semiconductor (CMOS) based integrated sensor system employing bacteriophage or phage organisms as recognition elements to detect deadly bacteria such as E-Coli and Salmonella. The system works on the basis of monitoring the changes in capacitance signals caused when the target bacteria get attached to the sensing interface. The system is designed using DALSA 0.8 mum technology and it consists of inter-digitized capacitor structures and signal detection and processing circuitry. The signal detection and processing is done by a charge based capacitance measurement (CBCM) circuit. The phage organisms are immobilized on the surface of the capacitor and together they form the sensing interface. We achieve a sensitivity of 29.3 mV/fF for the CMOS capacitive sensing interface, which corresponds to detecting infectious dose for the target bacteria. The system operates on a 5V DC supply and is estimated to consume an average power of 1.7 mW.

Brain Machine Interfaces combining Microelectrode Arrays with Nanostructured Optical Biochemical Sensors

Neural microelectrodes are an important component of neural prosthetic systems which assist paralyzed patients by allowing them to operate computers or robots using their neural activity. These microelectrodes are also used in clinical settings to localize the locus of seizure initiation in epilepsy or to stimulate sub-cortical structures in patients with Parkinsons disease. In neural prosthetic systems, implanted microelectrodes record the electrical potential generated by specific thoughts and relay the signals to algorithms trained to interpret these thoughts. In this paper, we describe novel elongated multi-site neural electrodes that can record electrical signals and specific neural biomarkers and that can reach depths greater than 8mm in the sulcus of non-human primates (monkeys). We hypothesize that additional signals recorded by the multimodal probes will increase the information yield when compared to standard probes that record just electropotentials. We describe integration of optical biochemical sensors with neural microelectrodes. The sensors are made using sol-gel derived xerogel thin films that encapsulate specific biomarker responsive luminophores in their nanostructured pores. The desired neural biomarkers are O2, pH, K+, and Na+ ions. As a prototype, we demonstrate direct-write patterning to create oxygen-responsive xerogel waveguide structures on the neural microelectrodes. The recording of neural biomarkers along with electrical activity could help the development of intelligent and more userfriendly neural prosthesis/brain machine interfaces as well as aid in providing answers to complex brain diseases and disorders.

Implantation of Elongated Porous Silicon Neural Probe Array in Rat Cortex

Neural microprobes represent an important component of neural prosthetic systems 14 where implanted microprobes record the electro-potentials generated by specific thoughts in the 15 brain and convey the signals to algorithms trained to interpret these thoughts. Here, we present 16 novel elongated multi-site neural probe that can reach depths greater than 10mm. We hypothesize 17 that reaching such depth allows the recording of cognitive signals required to drive cognitive 18 prosthetics. The impedance of the recording sites on the probes was on the order of 500 kΩ at 1 kHz, 19 which is consistent with probes used for neurophysiological recordings. The probes were made 20 porous using Xenon Difluoride (XeF2) dry etching to improve the biocompatibility and their 21 adherence to the surrounding neural tissue. Numerical studies were performed to determine the 22 reliability of the porous probes. We implanted the elongated probe in rats and show that the 23 elongated probes are capable of simultaneously recording both spikes and local field potentials 24 (LFPs) from various recording sites. 25

Bacterial immobilization and detection using porous silicon platform and CMOS sensory circuit

The paper presents the design of MEMS-based sensory system for real-time bacteria detection. The principle of functioning is based on monitoring the variation in capacitance signals owing to the adherence of target bacteria to the sensing interface. The system is designed using custom-based technology and it consists of comb finger capacitor structures made out of doped polysilicon. Aiming at improving the detection efficiency, the space between the comb fingers, forming the two electrodes of the capacitive sensor, will be made porous through a post-processing with Xenon Difluoride (XeF2) dry etching technique. This allows entrapping bacteria in between the electrodes thus increasing the variation of capacitance. This latter, is acquired using a Charge Based Capacitance Measurement (CBCM) sensory circuit built with to the 0.13 μm CMOS technology. The circuit is able to detect a difference in capacitance as low as 0.75 fF.