Integrated circuit design for implantable neural interfaces

Progress in microfabrication technology has opened the way for new possibilities in neuroscience and medicine. Chronic, biocompatible brain implants with recording and stimulation capabilities provided by embedded electronics have been successfully demonstrated. However, more ambitious applications call for improvements in every aspect of existing implementations. This thesis proposes two prototypes that advance the field in significant ways. The first prototype is a neural recording front-end with spectral selectivity capabilities that implements a design strategy that leads to the lowest reported power consumption as compared to the state of the art. The second one is a bidirectional front-end for closed-loop neuromodulation that accounts for self-interference and impedance mismatch thus enabling simultaneous recording and stimulation. The design process and experimental verification of both prototypes is presented herein

A 4-mode reconfigurable low noise amplifier for implantable neural recording channels

In this paper a reconfigurable implantable low noise amplifier for the recording of neural signals is presented. It is comprised by low-power and noise efficient current reuse OTAs in its direct path. The proposed architecture allows for an active feedback to set the high-pass corner in place of the commonly used pseudoresistor. Bandwidth selectivity is achieved by circuit reconfigurability which changes the pole frequencies of the system without impacting the total power consumption. Simulation results in AMS 0.18μm technology validate the proposed architecture in both nominal and corner process conditions with an estimated total power consumption of 454nW.Office of Naval Research (USA) N00014-14-1-0355Junta de Andalucía TIC 233

A 2.2 μW analog front-end for multichannel neural recording

In this paper an analog front-end for the multi-channel implantable recording of neural signals is presented. It is comprised by a two-stage AC-coupled low-noise amplifier (LNA) and a one stage AC-coupled variable gain amplifier (VGA). The proposed architecture employs highly power-noise efficient current reuse fully differential OTAs in the LNA stage and a fully differential folded cascode for the VGA stage. Simulation results in AMS 0.18μm validate the proposed architecture under process corners variations with an estimated power consumption of 2.2μm and 3.1 μVrms in-band noise.Ministerio de Economía y Competitividad TEC2016- 80923-POffice of Naval Research (USA) N00014111031

A Sub-µW Reconfigurable Front-End for Invasive Neural Recording

This paper presents a sub-μW ac-coupled reconfigurable front-end for the purpose of neural recording. The proposed topology embeds in it filtering capabilities allowing it to select among different frequency bands inside the neural signal spectrum. Power consumption is optimized by designing for bandwidth-specific noise targets that take into account the spectral characteristics of the input signal as well as the noise bandwidths of the noise generators in the circuit itself. An experimentally verified prototype designed in a 180 nm CMOS process draws a maximum of 815 nW from a 1 V source. The measured input-referred spot-noise at 500 Hz is 75 nV/√Hz while the integrated noise in the 200 Hz - 5 kHz band is 4.1 μVrms.Ministerio de Economía y Competitividad TEC2016-80923- PJunta de Andalucía TIC 233

A Sub-μVRms Chopper Front-End for ECoG Recording

This paper presents a low-noise, low-power fully differential chopper-modulated front-end circuit intended for ECoG signal recording. Among other features, it uses a subthreshold source-follower biquad in the forward path to reduce noise and avoid the implementation of a ripple rejection loop. The prototype was designed in 0.18μm CMOS technology with a 1V supply. Post-layout simulations were carried out showing a power consumption below 2μW and an integrated input-referred noise of 0.75μV rms , with a noise floor below 50 nV√Hz, over a bandwidth from 1 to 200Hz, for a noise efficiency factor of 2.7.Ministerio de Economía y Empresa TEC2016-80923-

A High TCMRR, Inherently Charge Balanced Bidirectional Front-End for Multichannel Closed-Loop Neuromodulation

This paper describes a multichannel bidirectional front-end for implantable closed-loop neuromodulation. Stimulation artefacts are reduced by way of a 4-channel H-bridge current source sharing stimulator front-end that minimizes residual charge drops in the electrodes via topology-inherent charge balancing. A 4-channel chopper front-end is capable of multichannel recording in the presence of artefacts as a result of its high total common-mode rejection ratio (TCMRR) that accounts for CMRR degradation due to electrode mismatch. Experimental verification of a prototype fabricated in a standard 180 nm process shows a stimulator front-end with 0.059% charge balance and 0.275 nA DC current error. The recording front-end consumes 3.24 µW, tolerates common-mode interference up to 1 Vpp and shows a TCMRR > 66 dB for 500 mVpp inputs.Ministerio de Economía y Competitividad TEC2016-80923-POffice of Naval Research (USA) N00014111031

A 32 Input Multiplexed Channel Analog Front-End with Spatial Delta Encoding Technique and Differential Artifacts Compression

This paper describes a low-noise, low-power and high dynamic range analog front-end intended for sensing neural signals. In order to reduce interface area, a 32-channel multiplexer is implemented on circuit input. Furthermore, a spatial delta encoding is proposed to compress the signal range. A differential artifact compression algorithm is implemented to avoid saturation in the signal path, thus enabling reconstruct or suppressing artifacts in digital domain. The proposed design has been implemented using 0.18 μm TSMC technology. Experimental results shows a power consumption per channel of 1.0 μW, an input referred noise of 1.1 μVrms regarding the bandwidth of interest and a dynamic range of 91 dB.Ministerio de Economía y Competitividad TEC2016-80923-POffice of Naval Research ONR N00014- 19-1-215

Evaluation of different methodologies for primary human dermal fibroblast spheroid formation: automation through 3D bioprinting technology

Cell spheroids have recently emerged as an effective tool to recapitulate native microenvironments of living organisms in an in vitro scenario, increasing the reliability of the results obtained and broadening their applications in regenerative medicine, cancer research, disease modeling and drug screening. In this study the generation of spheroids containing primary human dermal fibroblasts was approached using the two-widely employed methods: hanging-drop and U-shape low adhesion plate (LA-plate). Moreover, extrusion-based three-dimensional (3D) bioprinting was introduced to achieve a standardized and scalable production of cell spheroids, decreasing considerably the possibilities of human error. This was ensured when U-shape LA-plates were used, showing an 85% formation efficiency, increasing up to a 98% when it was automatized using the 3D bioprinting technologies. However, sedimentation effect within the cartridge led to a reduction of 20% in size of the spheroid during the printing process. Hyaluronic acid (HA) was chosen as viscosity enhancer to supplement the bioink and overcome cell sedimentation within the cartridge due to the high viability values exhibited by the cells -around 80%- at the used conditions. Finally, (ANCOVA) of spheroid size over time for different printing conditions stand out HA 0.4% (w/v) 60 kDa as the viscosity-improved bioink that exhibit the highest cell viability and spheroid formation percentages. Besides, not only did it ensure cell spheroid homogeneity over time, reducing cell sedimentation effects, but also wider spheroid diameters over time with less variability, outperforming significantly manual loading.We kindly thank Daniel García for their guidance with the rheological experiments. This work was supported by Programa de Actividades de I + D entre Grupos de Investigación de la Comunidad de Madrid, S2018/ BAA-4480, Biopieltec-CM, Programa Estatal de I + D + i Orientada a los Retos de la Sociedad, RTI2018-101627-B-I00 and Cátedra Fundación Ramón Areces. The experimental techniques used during this study were performed in the CleanRooms of Bioengineering, Universidad Carlos III de Madrid, Madrid, Spain