1. Introduction
Understanding the intricate correlation between individual neuron activities is pivotal for advancing the development of numerous applications within the realm of neuroscience [
1,
2]. Among these, a notable area of research focuses on investigating the mechanisms underlying the effects of neurodegenerative diseases such as Parkinson’s or Alzheimer’s, in light of their increasing global spread and the corresponding rise in treatment costs [
3,
4,
5,
6]. Additionally, ongoing research endeavors center around the development of efficient brain–machine interfaces (BMIs) for diagnostic and neuro-prosthetic purposes [
7,
8,
9].
However, to achieve breakthroughs in these and other areas of neuroscientific research, reliance solely on non-invasive methods of neural recording (i.e., EEG or fMRI) has proven to be insufficient. Although affordable and safe to perform, such techniques are hampered by limited spatial and temporal resolutions and exhibit a low signal-to-noise ratio (SNR) due to the filtering effect of the intermediate layers between the scalp and the source of the bio-signals [
10,
11]. Invasive neural recording through implantable neural probes, on the other hand, allows for the isolation of spike events from single neurons with sub-millisecond time precision by recording the neuronal activity directly from the extracellular space of the membrane [
12].
Multi-channel neural probes can be fabricated using a variety of techniques and materials. Most notably, silicon is widely favored on account of its cost-effectiveness, compatibility with standard fabrication processes, and the ability to integrate CMOS circuits on the same substrate [
13,
14]. Taking advantage of this aspect, recently introduced active neural probes have been a key factor in contributing to the gradual increase in the density of recording channels that can be implemented in a single probe’s shank. In turn, the number of individual neurons that can be simultaneously recorded has also experienced a steady rise [
15]. At the forefront of neural recording, devices such as Neuropixels 2.0, Neuroseeker, and SiNAPS have produced groundbreaking results when applied to small mammals and non-human primates [
16,
17,
18,
19,
20].
Designing CMOS neural probes presents a multifaceted challenge, involving various disciplines such as electronics, material science, and biology [
21,
22,
23]. While implanted micro-electrodes provide superior access to fine-grained neural activity, they inherently cover a smaller volume of brain tissue compared to standard non-invasive methods. Thus, future advancements must prioritize increasing the density and number of integrated recording sites to achieve large-scale brain coverage. Moreover, reducing the area occupied by neural probes can significantly decrease their invasiveness, which, in turn, decreases the risk of tissue damage during the probe’s insertion and reduces the chances of inflammatory response under chronic recording conditions [
24,
25,
26]. It is worth noting that down-scaling the technology to achieve a smaller area introduces short-channel effects of the MOS transistors, resulting in a reduction in transconductance and an increase in gate leakage current, flicker, and thermal noise power [
27].
Furthermore, optimizing power consumption in neural recording devices, and thus managing potential heat generation through dissipation, is a critical parameter [
28,
29]. Recent studies have shown that power consumption exceeding 40 mW leads to a temperature increase of over 2 °C, which, in turn, triggers neural cell death within a few days [
30].
Another important aspect to consider when designing neural probes is the ability of the circuit to effectively reject interferences, that is, the common-mode rejection ratio (CMRR) and the power supply rejection ratio (PSRR). To preserve the integrity of the acquired bio-signals and maintain a high SNR, both the common-mode signals, typically fed through the micro-electrodes, and the power supply noise, such as wall-mounted 50/60 Hz interference, should be rejected accordingly [
31]. Although various methods have been employed to ensure a high CMRR for the amplifiers employed in multi-channel neural probes, few studies have centered on the system CMRR in analog front ends [
32,
33,
34]. Typically, the system common-mode rejection ratio (SCMRR) in systems with a high channel count N decreases as N itself increases and is also dependent on the mismatch between the impedance of the reference electrode and the impedance of the signal-acquiring electrode.
In this regard, the novel approach introduced in [
34] aims to raise the SCMRR and the common-mode interference (CMI) range of a DC-coupled neural recording front end through the implementation of a shared voltage-averaging circuit (VAC) and a floating-rail common-mode feedback loop (CMFB). The latter employs an error amplifier with an open-loop gain of 45 dB that accepts as input the mean of the voltage outputs of the multiple input amplifiers and, in turn, produces a feedback voltage, used to retroactively cancel out any common-mode interference.
Similarly, in this work, we introduce the architecture of a DC-coupled analog front end designed for high-channel-count in-pixel neural recording systems. The described structure features 15 recording channels alongside a single reference channel. It incorporates a CMFB loop, which operates on the sum of individual channel currents to enhance both the SCMRR and the CMI range. In addition, the proposed design focuses on minimizing the on-chip area footprint of the front end, aligning with the demand for compact and efficient neural recording devices set by the state of the art.
The remainder of this paper is organized as follows.
Section 2 delves into the architecture of the front end, highlighting its innovative features. The topologies of the various components that make up the front end are presented in detail in
Section 3, while
Section 4 concerns the analytical aspects of the circuit’s performance. The results obtained through simulations are subsequently presented in
Section 5, along with a final table to compare the results with current state-of-the-art devices. The conclusions are drawn in
Section 6.
2. System Architecture
In order to effectively contextualize the novel contributions brought forth by the analog front end proposed in this document, it is necessary to first provide a characterization of the fundamental workings of the circuit outlined in [
34], thereby establishing a baseline for comparison. In this regard, the circuit depicted in
Figure 1 comprises 16 recording channels, 15 of which serve as input channels, while the remaining one acts as a reference channel. For local conditioning of the acquired bio-signals, each front-end channel integrates an in-pixel low-noise neural amplifier with a bandwidth of 7.5 kHz, ensuring coverage of both the action potentials and local field potentials recorded in the extracellular space. In a conventional IC multi-channel recording system, the total common-mode rejection ratio is dependent on the intrinsic CMRR of the input amplifiers, as well as the number of employed channels, as demonstrated in [
33]:
Here,
represents the input impedance of the low-noise amplifier, while
denotes the impedance of the recording electrode. The term
is used to quantify the difference in impedance between the reference electrode and the signal electrode, with a value of one indicating a condition of a perfect match. With the goal of improving the SCMRR and, therefore, increasing the CMI range in high-channel-count systems, the solution presented in [
34] employs a common-mode feedback loop based on the average sum of the output voltages of the input amplifiers.
The CMFB consists of a voltage-averaging circuit and an error amplifier. In relation to the single recording channel, the former is composed of a voltage buffer, necessary to eliminate the loading effect to the main amplifier, and a resistor
. Assuming the same value for all 16 resistors, the voltage fed to the inverting input of the error amplifier can be expressed as follows:
To complete the CMFB loop, the output of the error amplifier, denoted as , is fed back to the pixel amplifiers. As previously mentioned, the implementation of this kind of common-mode feedback loop enhances the SCMRR. However, it is important to acknowledge that including a voltage buffer for each recording channel results in a substantial increase in the on-chip area occupation, which is a critical aspect to consider in the context of neural recording devices.
To address this limitation, we devised a variation of the aforementioned front end, designed with the aim of significantly reducing its area occupation without compromising the system’s performance. As depicted in the block diagram in
Figure 2, this modified version of the front end maintains the same number of recording channels. Its distinctive feature lies in the operation mode of the CMFB loop: in place of the mean calculation of the output voltages, a sum of the output currents is conducted instead.
Summing the output signals as currents eliminates the need for voltage buffers and resistors, resulting in a significant reduction in the on-chip area occupation per recording channel. In particular, for each input amplifier, the voltage-averaging circuit is replaced with two much smaller transistors, while the current sum is made possible by implementing two common-gate transistors. In doing so, the voltage buffers and the resistors depicted in
Figure 1 are no longer required. As a result, the on-chip area occupation is significantly reduced.
3. Circuit Design
The following section of the paper delves deeper into the topologies of the various stages that comprise the proposed multi-channel neural recording front end, providing insight into the mechanisms underlying the amplifying stage and the CMFB loop.
3.1. Pixel DC-Coupled Amplifiers
The schematic of the primary low-noise amplifier utilized in each recording channel is depicted in
Figure 3. Following the topology proposed in [
34], transistors
M1 and
M2 form the DC-coupled inverter-based amplifier of the system. In contrast to commonly used configurations employing differential amplifiers, the utilization of single-ended amplifiers offers notable benefits, such as reduced area occupancy and power dissipation, albeit at the cost of a decreased system rejection to interfering common-mode signals and power supply variations.
For the i-th channel, the output current produced by the main inverter-based amplifier is duplicated by utilizing the replicating transistors M8 and M9, which share the same source and gate nodes as the transistors comprising the inverter itself. The magnitude of the duplicated current is determined by the transconductance of M8 and M9. As such, by adjusting the aspect ratios of M8 and M9 to a fraction of the ratios of transistors M1 and M2, it is possible to replicate a scaled current with precision. This is done to ensure a more efficient occupation of the on-chip area and a reduction in power consumption.
With reference to the schematic in
Figure 3, transistors
M3 and
M4 provide a way to set the voltages of the floating rails of the input pixel amplifier. Acting as the terminal of the CMFB loop of the system, these transistors are diode-connected to avoid strong variations in the output high-impedance node, which would otherwise require Miller compensation. Additionally, the pairs
M3–
M4 and
M1–
M2 must be sized equally in order to effectively reject common-mode interference and also to prevent an increase in the IRN caused by the eventual mismatch.
Biasing of the amplifier is achieved through the voltages
and
applied to the gates of transistors
M5 and
M6–
M7, which, respectively, act as a current source and a current sink for the inverter. Concerning the pair
M6–
M7 in particular, connecting the gate nodes and the body nodes of the two transistors allows us to virtually obtain a transistor with a channel length capable of exceeding the upper limit set by the specific adopted technology [
35].
3.2. Common-Mode Feedback Stage
The topology of the CMFB stage in the front end is structured around two common-gate transistors, namely
M11 and
M12, which are used to establish a low-impedance node for summing the scaled duplicated currents. Referring to the schematic presented in
Figure 4, node A serves as the summing node for the currents duplicated by the 16 NMOS replicating transistors, while node B provides the same function for the currents duplicated by the PMOS replicating transistors connected to the main amplifiers.
Transistors
M11 and
M12 effectively form two folded cascode structures, with the total scaled output current being converted into the input voltage of the error amplifier through the output resistance at their shared drain node. This voltage is subsequently amplified and fed back to the gate of the feedback amplifiers introduced in
Section 3.1.
In terms of biasing, transistors M10 and M13–M14 act as current sources and are employed to set the bias current for the branch of the CMFB stage. It must be noted that the pair M13–M14 is designed following the same principle as the pair M6–M7 that makes up one of the two current generators used to bias the inverter-based amplifier.
3.3. Error Amplifier
The topology of the error amplifier utilized to implement the CMFB loop is illustrated in
Figure 5. Designed to operate in weak inversion mode, the amplifier comprises three stages; transistors
M15,
M16,
M17,
M18,
M19, and
M20 form a differential active-load amplifying stage, with the signal coming from the inverting input. Note that a reference voltage is applied to the non-inverting input instead. Transistors
M19 and
M20 ensure the correct biasing of the stage and are driven by a voltage
applied to the shared gate node.
The second stage of the amplifier is made up of a common-source transistor,
M21, biased through the composite transistors
M22–
M23. A compensation feedback capacitor
is connected between the drain and the gate of
M21 to ensure the stability of the amplifier, as well as to provide a sufficient gain bandwidth product according to the following formula [
36]:
The final class AB stage implemented through M24–M25 guarantees a rail-to-rail output swing, which, in turn, allows for the overall front end to achieve a high CMI value.
5. Simulation Results
The proposed analog front end was designed and simulated following the 180 nm CMOS process from TSMC. This section delves into the layout design aspects of the DC-coupled pixel input amplifiers and provides sizing information concerning the various components. Additionally, it showcases the results obtained through extensive simulations.
5.1. Layout and Transistor Sizing
The layout of the analog front end is depicted in
Figure 9, showing the 16-pixel amplifiers, each with an area footprint of 50
m × 65
m, placed along two rows. Utilizing six metal layers, this compact layout encompasses all the transistors described in detail in
Section 3. Notably, the smaller transistors (
M8–
M9 in
Figure 3), responsible for replicating the scaled currents, are surrounded by the transistors of the main inverter and the feedback transistors to mitigate potential mismatch between the devices. Overall, the area occupation per channel is lower than 0.004 mm
2.
With reference to
Figure 3 and
Figure 4,
Table 1 summarizes the size parameters of the MOS transistors used in both the pixel amplifier and the CMFB stage that make up the closed loop. As stated previously, the transistors that make up the inverter and the feedback transistors are sized equally by design. In order to accurately scale the currents of the main amplifiers, feedback transistors
M8 and
M9 are sized with a width scaled by a factor of 4. Transistors
M5 and
M6–
M7 are sized with the intent of producing a bias current of 2.5
A for the main amplifying branch. Regarding the common-gate transistors implemented in the current-summing branch of the front end, the sizes are chosen to be equal to the replicating transistors to minimize area occupation. For biasing purposes, the
W and
L parameters of transistors
M10 and
M13–
M14 are chosen to generate a current at least equal to the sum of the scaled, replicated currents.
Table 2 displays the sizing choices made with respect to the error amplifier. In this case, the parameters of the transistors are set with the aim of obtaining a high open-loop gain for the amplifier of at least 80 dB, with a phase margin of 60°.
5.2. Circuit Simulations
The proposed front end’s nominal behavior was simulated within the Cadence Virtuoso environment. To achieve results that closely resemble the actual implementation of the neural recording system, simulations were conducted using the post-layout netlist with extracted parasitics. The circuit was biased with a dual voltage supply ( = = 0.5 V), while the total current used to bias a single channel was set at 3.5 A.
Figure 10 shows that the inverter-based pixel amplifiers integrated into each recording channel boasted a differential gain of 44.16 dB, alongside a high cutoff frequency exceeding 100 kHz. These metrics highlight the amplifiers’ ability to capture and amplify neural signals across the entire frequency spectrum, encompassing both local field potentials and action potentials as measured from the extracellular space.
As shown in
Figure 11, further simulations revealed a favorable SCMRR of 80.5 dB at low frequencies. Particularly noteworthy was the performance of the front end within the range between 0.1 Hz and 100 Hz, where the SCMRR maintained a value of at least 80 dB. A moderately high level of rejection was maintained at higher frequencies, with the SCMRR exceeding 60 dB up to a frequency of 2 kHz.
The PSRR of the front end, as indicated in
Figure 12, exhibited a value of 72.55 dB at frequencies in the range spanning from 0.1 Hz to 100 Hz. For higher frequencies, the measured PSRR exhibited a similar behavior to the SCMRR, maintaining a level above 60 dB up until 2 kHz.
The input-referred noise spectrum of the input amplifier is presented in
Figure 13, showing a noise level of 100 nV/
at 100 Hz and a value of 50 nV/
at 1 kHz. By integrating the noise spectrum across various frequency intervals, the noise performance of the amplifier was evaluated in terms of the IRN. Specifically, the considered frequency bands are those associated with the LFP signals (1 Hz–300 Hz), the action potentials (300 Hz–7.5 kHz), and the overall spectrum that characterizes the bio-signals recorded from the extracellular space (1 Hz–7.5 kHz). The resulting measurements, acquired by varying the number of channels, are reported in
Table 3.
As seen in the results reported in
Table 3, the IRN exhibited an increasing trend as the number of recording channels decreased. This is consistent with Equation (
31), highlighting the significance of the contribution of
, the noise source associated with the smaller replicating transistors, which became negligible when using at least eight channels.
A widely used figure of merit that allows us to relate the noise performance of the circuit with its power consumption and bandwidth is the noise efficiency factor (NEF) [
37], expressed as follows:
where
is the thermal voltage,
is the total supply current of the amplifier, and
is the amplifier’s bandwidth in Hz. By substituting the values of the total current required to bias the individual recording channel, the IRN, and the bandwidth into (
32), we obtain
In addition, the power efficiency factor (PEF) can be computed as
5.3. Process and Mismatch Simulations
To assess the robustness of the front end against PVT (Process, Voltage, and Temperature) and mismatch variations, the system underwent comprehensive testing via multiple simulations. Specifically, a Monte Carlo simulation comprising 200 iterations was conducted. The outcomes of these simulations are outlined in
Table 4.
It must be noted that both the differential gain and the common-mode gain of the front end demonstrated standard deviations within a 2 dB interval, consequently maintaining a similarly constrained SCMRR. Particularly, the differential gain exhibited minimal fluctuations around its mean value of 44.16 dB. Although the PSRR (power supply rejection ratio) variance was marginally higher, it remained moderately limited, with a mean of 74.11 dB and a variance of 6.30 dB. In both instances, the tested performance metrics yielded favorable results, with both figures of merits exceeding 70 dB on average.
Concerning the SCMRR and PSRR, histograms related to the distribution of results over the 200 Monte Carlo iterations are presented in
Figure 14 and
Figure 15.
To further test the robustness of the proposed front end, a parametric simulation focusing on temperature variations was conducted. By gradually varying the operating temperature within the range [0 °C–50 °C], the front end’s gain and noise parameters, along with the rejection parameters, were evaluated accordingly (
Table 5).
Regarding the differential gain of the input amplifiers, minimal fluctuations were observed; however, the common-mode gain of the system exhibited a gradual decrease in value as the test temperature rose. Consequently, the SCMRR displayed an increasing trend with rising temperatures, reaching a maximum value of 86.72 dB at 50 °C. Conversely, the PSRR of the system tended to decrease in value with rising temperatures. In the range corresponding to the physiological conditions of the brain [38 °C–41 °C], both the PSRR and SCMRR were characterized by relatively minor variations, maintaining values of around 70 dB and 80 dB, respectively. When examining the noise performance of the front end amidst temperature variations, it was expected that the IRN of the system would experience a gradual rise. Nevertheless, at 4.23 , considering the total bandwidth [1 Hz–7.5 kHz], barely exceeded its nominal value measured at 27 °C.
Continuing with the evaluation of the front end, the following batch of simulations was conducted by varying the power supply voltage ±10% of its nominal value. By consulting the results displayed in
Table 6, it can be seen that variations in the differential gain were once again minimal. In a similar manner, the common-mode gain of the system varied between a minimum of −39.21 dB for (
Vdd −
Vss) = 1.1 V and a maximum of −32.36 for (
Vdd −
Vss) = 0.9 V. Integrating the input noise spectrum across the bandwidths of interest revealed a minor increasing trend in the band related to the local field potentials [1 Hz–300 Hz] and a minor decreasing trend in the band related to the action potentials [300 Hz–7.5 kHz]. Overall, the IRN measured across the total frequency band exhibited a negligible decrease.
To conclude with the PVT analysis, the results of the simulations under corner variations are compiled in
Table 7. Generally, it can be observed that the front end’s robustness is quite favorable.
Table 8 shows a comparison between the front end proposed in this work and various analog front ends introduced in recent years. In terms of noise, SCMRR, PSRR, and power consumption per channel (P/Ch), the simulation results presented in this section are comparable with modern state-of-the-art findings. Of particular importance is the area occupation per recording channel (A/Ch), which, for our devised front end, was reduced by a factor of 3 with respect to the front end introduced in [
34], and was approximately one-tenth of the area occupied by the work presented in [
33]. Additionally, thanks to the implemented closed CMFB loop, the CMI range of the front end described here was significantly higher than those measured for other devices.