This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no 767092. Lecture 1: Integrated Circuits for implants MRUT Dust Department of Die Drug Aarhus University Container

PZT-4 μLED 10 November 2019 Storage Cap.

Target Light- Sensitive μELectrodes

Associate Prof. Farshad Moradi, ICE-LAB, Aarhus University LITERATURE TO READ

[1] S. A. Haddad, R. P. Houben, and W. Serdijin, “The evolution of pacemakers,” IEEE Engineering in Medicine and Biology Magazine, vol. 25, no. 3, pp. 38– 48, 2006. [2] J. D. Weiland and M. S. Humayun, “,” Proceedings of the IEEE, vol. 96, no. 7, pp. 1076–1084, 2008. [3] A. Rashidi, N. Yazdani, and A. M. Sodagar, “Fully-implantable, multichannel, microstimulator with tracking supply ribbon and energy recovery,” in 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Aug 2016, pp. 1818–1821. [4] J. K. Niparko, Cochlear implants: Principles & practices. Lippincott Williams & Wilkins, 2009. [5] A. L. Benabid, S. Chabardes, J. Mitrofanis, and P. Pollak, “ of the subthalamic nucleus for the treatment of parkinson’s disease,” The Lancet Neurology, vol. 8, no. 1, pp. 67–81, 2009. [6] A. M. Kuncel and W. M. Grill, “Selection of stimulus parameters for deep brain stimulation,” Clinical neurophysiology, vol. 115, no. 11, pp. 2431–2441, 2004. [7] H. Lee, K. Y. Kwon, W. Li, and M. Ghovanloo, “A power-efficient switched-capacitor stimulating system for electrical/optical deep brain stimulation,” IEEE Journal of Solid-State Circuits, vol. 50, no. 1, pp. 360–374, Jan 2015. [8] S. K. Moore, “Psychiatry’s shocking new tools [brain stimulation techniques],” IEEE spectrum, vol. 43, no. 3, pp. 24–31, 2006. [9] H. Lee, H. Park, and M. Ghovanloo, “A power-efficient wireless system with adaptive supply control for deep brain stimulation,” IEEE Journal of Solid- State Circuits, vol. 48, no. 9, pp. 2203–2216, Sep. 2013. [10] T. C. Chang, M. J. Weber, J. Charthad, S. Baltsavias, and A. Arbabian, “Scaling of ultrasound-powered receivers for sub-millimeter wireless implants,” in 2017 IEEE Biomedical Circuits and Systems Conference (BioCAS), Oct 2017, pp. 1–4

ICE-LAB, Aarhus University 3/57 LITERATURE TO READ

[11] M. J. Weber, A. Bhat, T. C. Chang, J. Charthad, and A. Arbabian, “A miniaturized ultrasonically powered programmable optogenetic implant stimulator system,” in 2016 IEEE Topical Conference on Biomedical Wireless Technologies, Networks, and Sensing Systems (BioWireleSS), Jan 2016, pp. 12–14.

[12] J. Charthad, T. C. Chang, Z. Liu, A. Sawaby, M. J. Weber, S. Baker, F. Gore, S. A. Felt, and A. Arbabian, “A mm-sized wireless implantable device for electrical stimulation of peripheral nerves,” IEEE Transactions on Biomedical Circuits and Systems, vol. 12, no. 2, pp. 257–270, April 2018.

[13] Y. Luo, J. Wang, W. Huang, J. Tsai, Y. Liao, W. Tseng, C. Yen, P. Li, and S. Liu, “Ultrasonic power/data telemetry and neural stimulator with ookpm signaling,” IEEE Transactions on Circuits and Systems II: Express Briefs, vol. 60, no. 12, pp. 827–831, Dec 2013.

[14] B. C. Johnson, K. Shen, D. Piech, M. M. Ghanbari, K. Y. Li, R. Neely, J. M. Carmena, M. M. Maharbiz, and R. Muller, “Stimdust: A 6.5 mm 3, wireless ultrasonic peripheral nerve stimulator with 82% peak chip efficiency,” in 2018 IEEE Custom Integrated Circuits Conference (CICC). IEEE, 2018, pp. 1–4.

[15] S. Hosseini et al., “Multi-ring ultrasonic transducer on a single piezoelectric disk for powering biomedical implants,” in 41st Ann. Int. Con. of the IEEE Eng. in Medicine & Biology Society, July 2019, pp. 3827– 3830.

[16] G. Shin, A. M. Gomez, R. Al-Hasani, Y. R. Jeong, J. Kim, Z. Xie, A. Banks, S. M. Lee, S. Y. Han, C. J. Yoo et al., “Flexible near-field wireless optoelectronics as subdermal implants for broad applications in ,” Neuron, vol. 93, no. 3, pp. 509–521, 2017.

[17] T.-i. Kim, J. G. McCall, Y. H. Jung, X. Huang, E. R. Siuda, Y. Li, J. Song, Y. M. Song, H. A. Pao, R.-H. Kim et al., “Injectable, cellularscale optoelectronics with applications for wireless optogenetics,” Science, vol. 340, no. 6129, pp. 211–216, 2013.

[18] K.-i. Inoue, M. Takada, and M. Matsumoto, “Neuronal and behavioural modulations by pathway-selective optogenetic stimulation of the primate oculomotor system,” Nature communications, vol. 6, p. 8378, 2015.

[19] G. Gagnon-Turcotte, M. N. N. Khiarak, C. Ethier, Y. De Koninck, and B. Gosselin, “A 0.13-µm cmos soc for simultaneous multichannel optogenetics and neural recording,” IEEE Journal of Solid-State Circuits, no. 99, pp. 1–14, 2018.

[20] G. Gagnon-Turcotte, Y. LeChasseur, C. Bories, Y. Messaddeq, Y. De Koninck, and B. Gosselin, “A wireless headstage for combined optogenetics and multichannel electrophysiological recording,” IEEE Transactions on Biomedical Circuits and Systems, vol. 11, no. 1, pp. 1–14, Feb 2017.

ICE-LAB, Aarhus University 4/57 LITERATURE TO READ

[21] J. Luo, K. Nikolic, B. D. Evans, N. Dong, X. Sun, P. Andras, A. Yakovlev, and P. Degenaar, “Optogenetics in : A neural processor for predicting optically active neural networks,” IEEE Transactions on Biomedical Circuits and Systems, vol. 11, no. 1, pp. 15–27, Feb 2017.

[22] G. Buzsaki, E. Stark, A. Ber ´ enyi, D. Khodagholy, D. R. Kipke, E. Yoon, ´ and K. D. Wise, “Tools for probing local circuits: high-density silicon probes combined with optogenetics,” Neuron, vol. 86, no. 1, pp. 92–105, 2015.

[23] R. Erfani, F. Marefat, A. M. Sodagar, and P. Mohseni, “Modeling and experimental validation of a capacitive link for wireless power transfer to biomedical implants,” IEEE Transactions on Circuits and Systems II: Express Briefs, vol. 65, no. 7, pp. 923–927, July 2018.

[24] R. Erfani and A. M. Sodagar, “Amplitude-engraving modulation (aem) scheme for simultaneous power and high-rate data telemetry to biomedical implants,” in 2013 IEEE Biomedical Circuits and Systems Conference (BioCAS), Oct 2013, pp. 290–293.

[25] H. Lee and M. Ghovanloo, “An integrated power-efficient active rectifier with offset-controlled high speed comparators for inductively powered applications,” IEEE Transactions on Circuits and Systems I: Regular Papers, vol. 58, no. 8, pp. 1749–1760, Aug 2011.

[26] C. Huang, T. Kawajiri, and H. Ishikuro, “A near-optimum 13.56 mhz cmos active rectifier with circuit-delay real-time calibrations for highcurrent biomedical implants,” IEEE Journal of Solid-State Circuits, vol. 51, no. 8, pp. 1797–1809, Aug 2016.

[27] K. Noh, J. Amanor-Boadu, M. Zhang, and E. Snchez-Sinencio, “A 13.56-mhz cmos active rectifier with a voltage mode switched-offset comparator for implantable medical devices,” IEEE Transactions on Very Large Scale Integration (VLSI) Systems, vol. 26, no. 10, pp. 2050–2060, Oct 2018.

[28] H. Cha, W. Park, and M. Je, “A cmos rectifier with a cross-coupled latched comparator for wireless power transfer in biomedical applications,” IEEE Transactions on Circuits and Systems II: Express Briefs, vol. 59, no. 7, pp. 409–413, July 2012.

[29] M. J. Weber, Y. Yoshihara, A. Sawaby, J. Charthad, T. C. Chang, and A. Arbabian, “A miniaturized single-transducer implantable pressure sensor with time-multiplexed ultrasonic data and power links,” IEEE Journal of Solid-State Circuits, vol. 53, no. 4, pp. 1089–1101, April 2018.

[30] H. Sadeghi Gougheri and M. Kiani, “An inductive voltage-/current-mode integrated power management with seamless mode transition and energy recycling,” IEEE Journal of Solid-State Circuits, vol. 54, no. 3, pp. 874– 884, March 2019.

ICE-LAB, Aarhus University 5/57 LITERATURE TO READ

[31] C. Kim, J. Park, A. Akinin, S. Ha, R. Kubendran, H. Wang, P. P. Mercier, and G. Cauwenberghs, “A fully integrated 144 mhz wirelesspower-receiver-on-chip with an adaptive buck- boost regulating rectifier and low-loss h-tree signal distribution,” in 2016 IEEE Symposium on VLSI Circuits (VLSI-Circuits). IEEE, 2016, pp. 1–2.

[32] C. Kim, S. Ha, J. Park, A. Akinin, P. P. Mercier, and G. Cauwenberghs, “A 144-mhz fully integrated resonant regulating rectifier with hybrid pulse modulation for mm-sized implants,” IEEE Journal of Solid-State Circuits, vol. 52, no. 11, pp. 3043–3055, 2017.

[33] R. Erfani, F. Marefat, and P. Mohseni, “A 110mhz frequency-aware cmos active rectifier with dual-loop adaptive delay compensation and ¿230 mw output power for capacitively powered biomedical implants,” in 2019 IEEE Custom Integrated Circuits Conference (CICC), April 2019, pp. 1–4.

[34] A. Rashidi, K. Laursen, S. Hosseini, and F. Moradi, “An ultrasonically powered optogenetic microstimulators with power-efficient active rectifier and charge reuse capability,” in 2019 IEEE International Symposium on Circuits and Systems (ISCAS). IEEE, 2019, pp. 1–5.

[35] P. Allen and D. Holberg, CMOS Analog Circuit Design. New York: Oxford University Press, 2012.

[36] Rail-to-Rail, Very Fast, 2.5 V to 5.5 V, Single-Supply TTL/CMOS Comparators, Analog Devices, Jun. 2010, rev. A.

[37] A. Rashidi et al., “Overvoltage protection circuits for ultrasonically powered implantable microsystems,” in 41st Ann. Int. Con. of the IEEE Eng. in Medicine & Biology Society (EMBC), July 2019, pp. 4354–4358.

[38] M. Ghovanloo and K. Najafi, “Fully integrated wideband high-current rectifiers for inductively powered devices,” IEEE Journal of Solid-State Circuits, vol. 39, no. 11, pp. 1976– 1984, Nov 2004.

[39] A. Rashidi, N. Yazdani, and A. M. Sodagar, “Fully-integrated, highefficiency, multi-output charge pump for high-density microstimulators,” in 2018 IEEE Life Sciences Conference (LSC), Oct 2018, pp. 291–294.

[40] D. L. Miller, “Safety assurance in obstetrical ultrasound,” in Seminars in Ultrasound, CT and MRI, vol. 29, no. 2. Elsevier, 2008, pp. 156–164.

ICE-LAB, Aarhus University 6/57 GENERAL ARCHITECTURE OF A BRAIN IMPLANT

Power & Power Managment Recording Electrodes Main Controller Data Link Digital Signal Rectifier Programable Analog to Analog Battery gain digital processor frontend controller converter Regulator Data RF Link Recording Unit Modultor Reference generator Inductive Stimulation Unit link Stimulation Local Power on reset charge Stimulatin controller stimulation Capacitive balancer backend link controller Data DC/DC converter Demodulator Ultrasonic link Stimulation Electrodes / µLED

ICE-LAB, Aarhus University 7/57 Brain Stimulation

ICE-LAB, Aarhus University 8/57 DIFFERENT TYPES OF BRAIN STIMULATION

• Electroconvulsive therapy • Triggering a short seizure by applying DC current to some electrodes on the patient’s scalp while the patient is anesthetized. • Applications: For treating some brain disorders such as bipolar disorder and schizophrenia • Potential side effects: memory loss, headaches, muscle aches, • Transcranial Magnetic Stimulation • A non-invasive brain stimulation approach that uses focused electromagnetic fields to stimulate specific regions of the brain • Application: For treating depression • Two types: Repetitive transcranial magnetic stimulation, and Magnetic seizure therapy • Battery-powered Deep brain stimulator • Composed of a battery & pulse_generator implanted in the patient’s chest, subcutaneous wires to carry the electrical pulses to under the skull, and couple of electrodes penetrated deep into the brain for applying electrical stimulation. • Applications: treating Parkinson’s disease, anesthesia, depression, etc • The battry needs to be replaced every 10 years through another surgery • Wireless brain stimulators • Composed of an implanted unit under the skull that harvest the power transmitted by an external module • The commands for stimulation are usually embeded in the power signals • Applications: Deep brain stimulation (treating Parkinson’s disease, anesthesia, depression, etc), cortical visual prosthesis, etc.

ICE-LAB, Aarhus University 9/57

• ’ intercellular rest potential is around -60mV. +40 • There are some channels on the neuron’s body that are sensitive to the intracellular potential. If the potential increases to around -50mV (Thereshold), the aforementioned channels open and some ions

are moving into and outside of the neuron’s body that results in an action potential. potential (mV) potential • The action potentials travel to the synapses with next neurons to contribute to activating an action Threshold potential potential in the next neurons. -50 • Initiating of action potentials happen in the brain by means of some elctro-chemical -60 Resting potential neurotransmitters -70 Intracellular Intracellular Time

Trigger zone

Synapse

Electro-Chemical signal

ICE-LAB, Aarhus University 10/57 ELECTRICAL STIMULATION

• In electrical stimulation initiating the action potentials occurs by injecting some electrical charges to the target tissue, in order to increase the intracellular potential to threshold potential by means of some electrodes. • The model for the stimulation electrodes and the tissue between them can be simplified to a RC load for the stimulator. • Charge-balanced stimulation: It is important for tissue safety to remove the injected charges after the stimulation. Otherwise the accumulation of residual charges results in tissue corruption.

ICE-LAB, Aarhus University 11/57 DIFFERENT TYPES OF ELECTRICAL STIMULATION FRONT-END

• Voltage Controlled stimulation (VCS): Applying a controlled voltage to the electrodes in interface with target tissue.  Simple design  High power efficiency X Low safety due to lack of control on the charge injected to the tissue • Current Controlled Stimulation (CCS):Applying a controlled current to the electrodes in interface with target tissue.  High safety X Low efficiency • Switched Capacitor based Stimulation (SCS):Applying a controlled electrical charge to the electrodes in interface with target tissue using switched capacitor circuits.  High safety • Moderate design complexity J. Simpson and M. Ghovanloo “An experimental study of voltage, current, and charge controlled stimulation • Moderate efficiency front-end circuitry,” IEEE International Symposium on Circuits and Systems,2017.

ICE-LAB, Aarhus University 12/57 OPTOGENETIC STIMULATOIN

• In optogentics, some light-sensitive ion channels (called opsins) are added to the target neurons by genetically manipulation process (i.e. injection of some viruses). Then the excitation/inhibition happens by exposing the neurons to the specific light wavelength that the opsins are designed for. • Channelrhodopsin-2 (ChR2) is one of the popular opsins that is sensitive to the blue light. Typical light intensity requirement for stimulation of ChR2 is 1-10 mW/mm2, duty cycle of 20% and repetition rate of 50Hz. • Main advantage: higher neural selectivity in comparison with the electrical stimulation • Delivering light to the target neurons are usually done by F. Wu et al, “Monolithically Integrated μLEDs Photo: John P. Carnett/Popular means of optical fibers or micro LED(s). on Silicon Neural Probes for High-Resolution Science/Getty Images Optogenetic Studies in Behaving Animals ,” Neuron, 2019

ICE-LAB, Aarhus University 13/57 Powering implants

ICE-LAB, Aarhus University 14/57 BATTERY-POWERED IMPLANTS

• A long life-time for the battery requires a large battery that needs to be implanted in the patient’s chest due to larger free space. • subcutaneous interconnects are usually required to route the power or stimuli to the stimulation site. • Still, the battery shortage may force the patient to undergo another surgery for battery replacement. • Subcutaneous interconnects are prone to loose conection.

Battery Loose T. K. Schiefer et al, “Moving Forward: Advances in the Treatment of Movement shortage connection Disorders with Deep Brain Stimulation,” Frontiers in Integrative , 2011

ICE-LAB, Aarhus University 15/57 INDUCTIVE NEAR-FIELD POWER LINK

• Composed of a couple of coils in two side of tissue. • Applying an AC signal to the a transmitting coil (TX) produces a magnetic field (B) that induces an electromotive force across the terminals of the receiving coil (RX) to be used as the power source of the implant.

• Power Transfer Efficeincy (PTE) is the ratio of PRX tp PTX. • Contribute factors to poor PTE: Loose coupling (large separations, misalignments), coil losses (eddy effect and proximity effect), transmitter–receiver mismatch, and the tissue losses. K. Agarwal, et al ”Wireless power transfer • Resonant coupled coils at the transmitter and the strategies for implantable bioelectronics”, IEEE reciver are the first step for increasing the PTE REVIEWS IN BIOMEDICAL ENGINEERING, 2017.

ICE-LAB, Aarhus University 16/57 CAPACITIVE NEAR-FIELD POWER LINK

• In this approach two metal plates are placed over the tissue outside the body (TX plates) and two other metal plates are put in parallel to them inside the body (RX plates). Which results in two capacitors with tissue as its dielectirc. • AC electric field produced by the TX metal plates supports current displacement at RX plates that enable energy transfer to the implant. • In order to deliver high levels of power with moderate efficiencies edge-to-edge distance between the two pairs of K. Agarwal, et al ”Wireless power transfer parallel plates requires to be large (e.g., > 10cm). The PTE is strategies for implantable bioelectronics”, IEEE REVIEWS IN BIOMEDICAL ENGINEERING, 2017. usually lower than inductive link. • Capacitive link is less sensitive to EM interference and misalignment in comparison to Inductive link.

ICE-LAB, Aarhus University 17/57 FAR-FIELD RF LINK

• Composed of a set of transmitting and receiving antennas • Small antennas that can be fabricated on chip • High tissue absorbtion due to high frequency • Omnidirectional and consequently low

PTE Hamid Basaeri et al, “A review of acoustic power transfer for biomedical implants,” Smart Materials and Structures, 2016.

ICE-LAB, Aarhus University 18/57 Ultrasonic Power Link

ICE-LAB, Aarhus University 19/57 WHY ULTRASOUND?

NF: Near field (i.e. Inductive) RF: Far field (Radio Frequency) US: Ultrasound

Power limits: NF, RF: 10 − 100 휇푊/푚푚2 US: 7.2 푚푊/푚푚2

A. Arbabian, et.al. Dec 2016. Sound technologies, sound bodies: Medical implants with ultrasonic links, IEEE Microwave Magazine

ICE-LAB, Aarhus University 20/57 ADVANTGAGES OF ULTRASONIC POWER LINK

• According to U.S. Food and Drug Administration’s (FDA’s) standard, allowed spatial-peak temporal-average acoustic intensity in exposure to body is 7.2mW/mm2 for biomedical applications which is about two order of magnitude higher than the exposure limit for RF signals. • Due to the smaller wavelength of ultrasonic waves in comparison to the electromagnetic waves, The attenuation coefficient of the power carrier in ultrasonically powered microsystems is several order of magnitude smaller than their RF/inductive counterparts, which makes them suitable for deeply placed implants. • Since the acoustic waves cannot interfere with electromagnetic fields, ultrasonically powered microsystems are not vulnerable to the severe electromagnetic fields like during MRI or security check in airports.

ICE-LAB, Aarhus University 21/57 LINK EFFICIENCY

~ ~ ~ VRec

Signal Generator PTX PRX av P ,

Elec,TX in

Load

Load

P

Elec

P

R

P

DC DC Converter

- Matching Circuit Ultrasonic AC Tissue

Transducer Piezoelectric Piezoelectric Receiver ~ ~ ~ GND

푃퐸푙푒푐,푇푋 푃퐸푙푒푐,푇푋 푃푇푋 푃푅푋 푃퐸푙푒푐,푎푣 푃𝑖푛 휂푡표푡 = = × × × × = 휂푇푋 × 휂푃푟표푝푎𝑔푎푡𝑖표푛 × 휂퐴푝푒푟푎푡푢푟푒 × 휂푀푎푡푐ℎ × 휂퐶ℎ𝑖푝 푃퐿표푎푑 푃푇푋 푃푅푋 푃퐸푙푒푐,푎푣 푃𝑖푛 푃퐿표푎푑

ICE-LAB, Aarhus University 22/57 PIEZOELECTRIC MATERIALS

• Piezoelectric materials generate electric charge from mechanical stress and conversely converts electric fields into mechanical strain

• Atomic size differences displaces atoms slightly generating electric dipole moments that gives rise to a macroscopic polarisation. The extent of the polarisation can be changed by exerting a mechanical force on the material.

• In a circuit, the material can act as an energy source when continuously mechanically stimulated for instance through soundwaves as it is done in the STARDUST project

ICE-LAB, Aarhus University PIEZOCERAMICS FOR BIOLOGICAL APPLICATIONS

• Many of the best performing piezoceramic materials contain toxic elements like lead, Pb, which makes them unsuitable for implantation in • Within the field of piezoceramics much effort is thus directed towards the development of new materials made from nontoxic elements • This task is comprised of working towards novel materials by experiments as well as theoretical predictions but also by optimisation of existing materials for instance through the addition of dopant elements or from texturing, both of which have great influence on the piezoelectric response properties

• In the STARDUST project we work with the niobate K0.5Na0.5NbO3 which is currently a hot topic as it has shown a performance similar to some types of PZT whilst being made up of non-toxic elements

ICE-LAB, Aarhus University PIEZOCERAMICS FOR BIOLOGICAL APPLICATIONS

• The currently most widespread piezoceramic material is PZT which contains lead making it unsuitable for biomedical applications. When chosing materials for biomedical applications, toxicity as well as performance are important things to consider.

Solid state chemistry and its applications / Anthony R. West. – Second edition

• In the STARDUST project we work with the niobate K0.5Na0.5NbO3 which is currently a hot topic as it has shown a performance similar to some types of PZT whilst being made up of non-toxic elements as well as having a high Tc allowing for sterilisation prior to biomedical application.

ICE-LAB, Aarhus University PIEZOCERAMICS FOR BIOLOGICAL APPLICATIONS • Some of the best performing piezoelectric materials include titanates, zirconates and niobates, e.g., PZT Pb(ZrxTi1-x)O3, BaTiO3, Bi4Ti3O12 and KNbO3 and NaNbO3 • The choice of material for biomedical applications is however not only about the performance; the toxicity is also crucial. Lead is a heavy metal and thus unsuitable for applications in humans

• In the STARDUST project we work with the niobate K0.5Na0.5NbO3 which is currently a ”hot material” as it has shown a performance similar to some types of PZT whilst being comprised of non-toxic elements. It also has a high enough Curie temperature to allow for sterilisation of implants without degrading the material as opposed to, for instance, BaTiO3

ICE-LAB, Aarhus University MODELS FOR ULTRASONIC LINKS

• Lumped Element Models u1 u2 Z0,M Z0,M

Easy to implement in IC- Acoustic Z0,B Acoustic Z0,P , t/2 Z0,P , t/2 Z , t Z0,B design CAD tools Source Source 0,P

Proper for behavioral u1-u2 C0 C0 Ielec Xp + (h33×Ielec)/s Z - L + analysis ZL [h ×(u -u )]/s - 33 1 2

× One-dimensional models ZP,elec Z a) KLM Model P,elec b) Leach Model • Finite Element Methods Multi-physics simulation × Time-consuming simulations × No well-developed interface with IC-design CAD tools

ICE-LAB, Aarhus University 27/57 CRYSTAL MODEL 1: KLM MODEL

The good: • “Go-to” model in literature. • Useful for frequency analysis.

The bad: • No transient analysis without simplification.

The ugly: • Simplified model losses all dynamic mechanical and electrical coupling effects. A. Arbabian, et.al, “Sound technologies, sound bodies: Medical implantswith ultrasonic links”, IEEE Microwave Magazine, 2016.

ICE-LAB, Aarhus University 28/57 CRYSTAL MODEL 2: LEACH MODEL

W. M. Leach, 1994

ICE-LAB, Aarhus University 29/57 CRYSTAL MODEL 2: LEACH MODEL

Acoustic Acoustic The good: Front Port Back Port R T1 (Z0, TD) R • Same frequency response as the KLM water water model. Acoustic • Easy to implement simulators. Power V퐴푐표푢푠푡𝑖푐 Source I1

V퐸 The great: 1 • Directly useful for transient analysis. V • Transient start at zero power! 4 C R I 1 1 F2 1F 1TΩ The beauty:

• No loss of dynamic coupling effects I2 between the mechanical and electrical. E+ R Electrical IF C 0 • Elegantly represents limited power. 1 0 1TΩ Port E-

ICE-LAB, Aarhus University 30/57 COMSOL

• What? • Numerical and finite element method (FEM) • Pros • Multiphysics modeling • Zero (0D) to three dimensional (3D) models • Various studies like frequency, time, and … • Ability for optimization • Link to Solidworks, Matlab, and … • Cons: • Time-consuming simulations in 3D

ICE-LAB, Aarhus University 31/57 COMSOL

• 3D  2D axially symmetric • Absorbing layer Absorbing layer • PZT-4 as transmitter and receiver

Piezoelectric Receiver

Water Domain

Piezoelectric Transmitter

ICE-LAB, Aarhus University 32/57 COMSOL MODELING

Table of Parameters Optimization of transmitter and receiver Parameter Description Value

푑2 Receiver’s diameter

푡2 Receiver’s thickness

푑 Powering distance 2 푚푚

푓푟 Resonance frequency 푡2

푚Τ 푑2 푐 Velocity in water 1483 푠 2 푐 푑 휆푤 Wavelength in water 푓 = 휆푤

2 푑1 Transmitter’s diameter 푑1 푡 푑 = 1 4휆 푑1 푤 2 푡1 Transmitter’s thickness 휆푃푍푇 2

ICE-LAB, Aarhus University 33/57 Ultrasonic Data Link

ICE-LAB, Aarhus University 34/57 DOWNLINK DATA TELEMETRY

• from the outside-the-body device to the implant • Sending commands or configuration data to the implant • Low data rate required • Data carried over the same power signals

ICE-LAB, Aarhus University 35/57 UPLINK DATA TELEMETRY

• from the implant to the outside- the-body device • Sending out measured physiological parameters or recorded neural activity • Higher data rate required • Three types: • Hybrid telemetry scheme • Direct modulation • Back-scattering scheme

ICE-LAB, Aarhus University 36/57 BACK-SCATTERING SCHEME

Forward Ultrasonic waves

Ultrasonic Transducer DUST

0 0 0 0 0 1 1 1 1 1 1 1 Modulated Backscattered signal

ICE-LAB, Aarhus University 37/57 Z0,M

Acoustic Z , D Z , t/2 Z , t/2 Source 0,M 0,P 0,P Z0,B

Zaco,M Zaco,P ZA ZB

C REFLECTION FACTOR Xp 0 Zele ZL

• Using KLM Model and Matlab simulations, it can be shown that the reflection factor from the piezo surface can be tuned to be between 1-99% just by changing the electrical load

• 1 mm3-sized PZT-4 crystal • 1.84 MHz

• XL = −9.3 kΩ

ICE-LAB, Aarhus University 38/57 LOAD SHIFT KEYING (LSK) WITH CONTINUOUS POWERING

V_REC

)

V

Active Diode 1 Active Diode 2 (

+ signal

R

C

Modulation Modulation Stor

+ Load

)

V

Comp Comp ( MS1 MS2 -

-

Voltage Voltage Rectifeid Rectifeid

IN1 IN2

)

V (

M3 MS3 MS4 M4 Modulation

signal

Modulated Modulated Backscattered signal signal Backscattered

Time(µs)

ICE-LAB, Aarhus University 39/57 Ultrasonically Power Microsystems

ICE-LAB, Aarhus University 40/57 NEURAL DUST

• The system is developed for recording in deep peripheral nervous system using backscattering scheme. • In this system, a transistor in triode region is derived by the neural signal recorded from two electrodes. The source and drain of this transistor is connected to a piezoelectric crystal terminals and thus changes the electrical load of the crystal based on recorded signal form electrodes. The crystal is exposed to some ultrasonic waves and the reflection of the signal from the crystal is measured. The recorded neural signal is recreated out of the measured reflections of the ultrasonic waves, since the amplitude of reflections are modulated by the variable electrical load due to neural signal. Dongjin Seo, et al, "Wireless recording in the • Even though it is very good proof of concept for backscattering peripheral communication scheme, since the only active device in this system nervous system with ultrasonic is the transistor in triode region, it is not expandable to other neural dust," applications. Neuron, Aug. 2016.

ICE-LAB, Aarhus University 41/57 STIMDUST

• This system proposes a fully programmable stimulator powered by ultrasonic signals. • The commands for stimulation are embedded in duration of silent notches of UPBs. The durations are measured using a Time to Digital Converter (TDC) and fed into a state machine to control different phases of stimulation. • The quiescent power is designed to be very low (4 µW) and the chip efficiency is reported as high as 82%.

B. C. Johnson, et al, “Stimdust: A 6.5 mm 3, wireless ultrasonic peripheral nerve stimulator with 82% peak chip efficiency,” in 2018 IEEE Custom Integrated Circuits Conference (CICC), 2018. MINIATURIZED PRESSURE SENSOR

• Using time-multiplexing method, a single piezoelectric crystal is used for harvesting energy and direct modulation for uplink data transmission. • The IC is equipped with an Ultrasonic Power Burst (UPB) detector. In presence of UPB the storage capacitor gets charged and some circuits like LDO get disabled for energy saving. At the end of UPB, there is a waiting period for dissipation of ultrasonic echoes and the the body pressure is measured, packed and sent out by OOK modulation of the same piezoelectric crystal. • Specific consideration is taken into account for

avoiding device breakdown during availability of UPB. M. J. Weber et al, "A miniaturized Single-Transducer implantable Pressure sensor With time-multiplexed ultrasonic data and power Links," IEEE Journal of Solid States circuits, 2018.

ICE-LAB, Aarhus University 43/57 STARDUST PROJECT (ENVISIONED)

• Energy efficient and selective MRUT Ultrasonic Link Dust Integrated circuit Die Drug • Low-area and energy-efficeint Container integrated circuits PZT-4 • Optogenetic stimulation μLED Storage Cap.

• In-site Electrophysiology Target Light- • ultra-locolized drug delivery Sensitive Neuron μELectrodes

ICE-LAB, Aarhus University 44/57 Our proposed Ultrasonically Powered System for Optogenetic Stimulation with Power-Efficient Active Rectifier

Accepted to be published in:

IEEE Transaction of Biomedical Circuit and Systems

ICE-LAB, Aarhus University 45/57 ACTIVE RECTIFIER

• AC-DC converters are inevitable for wirelessly powered microsystems including active circuits. • In wirelessly powered implants, active rectifiers are more popular in comparison to the passive ones due to their higher Voltage Conversion Ratio (VCR) and Power Conversion Efficiency (PCE). • In our design we designed an active rectifier for converting the AC signal at the piezoelectric receiver to a DC voltage for drive the µLED for optogenetics.

Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Comp1 264µm/ 264µm/ Comp2 - 0.18µm 0.18µm -

C IN1 Stor Current MS3 MS4 290µm/ 290µm/ Limiter 0.35µm 0.35µm

IN2

ICE-LAB, Aarhus University 46/57 Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Comp1 264µm/ 264µm/ Comp2 - 0.18µm 0.18µm -

C IN1 Stor Current MS3 MS4 290µm/ 290µm/ Limiter CONVENTIONAL ACTIVE RECTIFIER 0.35µm 0.35µm IN2

• Avoiding PCE degradation in MHz–range frequencies is still challenging in design of active rectifiers. • For maximizing the PCE we need to maximize the Forward Conduction time and minimize the Reverse Conduction time

IN1 IN2 V_REC Reverse Conduction time Vin,min Vin,min Forward conduction Reverse conduction

Forward X Conduction time

td,R tP,F Td,F tp,R

ICE-LAB, Aarhus University 47/57 STATE-OF-THE-ART SOLUTIONS

• Circuit techniques for increasing comparator’s speed: • Offset calibration techniques for delay compensation:

H. Cha et al, “A CMOS rectifier with a cross-coupled latched comparator H. Lee and M. Ghovanloo, “An integrated power-efficient active for wireless power transfer in biomedical applications,” IEEE rectifier with offset-controlled high speed comparators for Transactions on Circuits and Systems II: Express Briefs, July 2012. inductively-powered applications,” IEEE Transaction on Circuits and Systems I, Regular Papers, 2011.

ICE-LAB, Aarhus University 48/57 WHAT ELSE?

Lowering Rail to Rail Supply (LR2RS)

• Vin,min= R2RS/ADC

• tP = R2RS /(2×SlewRate) • Lower R2RS  Normal LV transitors  Less parasitics  higher SR  smaller tP

ICE-LAB, Aarhus University 49/57 HOW TO LOWER THE RAIL TO RAIL SUPPLY

Getting advantage of two available power supply rails (V_REC and V_LDO)

Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Voltage Comp1 264µm/ 264µm/ Comp2 - 0.18µm 0.18µm - V_LDO Double- Pass Referece Regulator Pas/Act Pas/Act C IN1 Stor Neural C Current Burst MS3 MS4 LDO Recording 290µm/ 290µm/ 77 pF Limiter Detector 0.35µm 0.35µm Front-End

IN2 • Lowering the rail to rail supply  Higher speed for comparator • Reusing the power consumed for switching and biasing the comparator by the circuits powered by the regulator

ICE-LAB, Aarhus University 50/57 Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Voltage Comp1 264µm/ 264µm/ Comp2 ROPOSED CTIVE - 0.18µm 0.18µm - V_LDO Double- Pass Referece P A Regulator Pas/Act Pas/Act C IN1 Stor Neural C Current Burst MS3 MS4 LDO Recording En 290µm/ 290µm/ 77 pF Limiter IODE Detector 0.35µm 0.35µm Front-End D IN2

V_REC • Common-gate

M1 Comp1 comparator M8 10µm/ V_BP1 4µm/ 0.5µm M10 0.3µm M6 M7 2µm/ • Dynamic bulk 0.6µm/ 0.6µm/ 0.3µm 0.3µm 0.3µm biasing circuit for MS1 BUF 264µm/ M11 0.18µm 2µm/ avoiding latch-up 0.3µm

M3 M4 • M5 Passive operation 0.25µm/ 0.5µm/ Dynamic Bulk 0.5µm/ SU 0.25µm 0.25µm Biasing circuit 0.25µm mode during start- V_LDO up and in absence

SU Pas/Act IN1 of Ultrasonic power bursts at the dust

ICE-LAB, Aarhus University 51/57 Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Voltage Comp1 264µm/ 264µm/ Comp2 - 0.18µm 0.18µm - V_LDO Double- Pass Referece Regulator PROPOSED DOUBLE-PASS Pas/Act Pas/Act C IN1 Stor Neural C Current Burst MS3 MS4 LDO Recording En 290µm/ 290µm/ 77 pF Limiter Detector 0.35µm 0.35µm Front-End REGULATOR IN2

V_REC • If ILDO > IRU , then Active Diode 1 series pass regulator IRU2 + MS1 Comp1 264µm/ supplies the extra 0.18µm M1 - CGS1 IRU1 24µm/ ISeries IN1 required current 0.3µm V_LDO

ILDO IShunt • If ILDO < IRU , then R1 V_Ref - 70 k V_Ref + M2 CLDO shunt pass regulator OpAmp1 OpAmp2 R 25µm/ 77 pF LDO + - 0.18µm drains the extra 1 µA recovered current to Series Pass Regulator Shunt Pass Regulator the ground

ICE-LAB, Aarhus University 52/57 Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Voltage Comp1 264µm/ 264µm/ Comp2 - 0.18µm 0.18µm - V_LDO Double- Pass Referece Regulator Pas/Act Pas/Act C IN1 Stor Neural C Current Burst MS3 MS4 LDO Recording En 290µm/ 290µm/ 77 pF Limiter REFERENCE GENERATOR Detector 0.35µm 0.35µm Front-End

IN2

V_REC

M7 • Conventional Voltage reference R2 M8 2.5µm/ 1 M 2.5µm/ 0.5µm 0.5µm • V_BP1 V_Ref=1.46V M6 M5 5µm/ M11 5µm/ • IRef =1 µA 0.6µm 12µm/ 0.6µm 0.35µm V_BP2 SU V_Ref • Digitally buffered Start-up M10 M4 M3 6µm/ 2µm/ 4µm/ 0.7µm 0.7µm 0.7µm citcuit can be reused for the V_BN1 M9 M2 M1 active diodes

12µm/ 4µm/1µm 8µm/1µm Voltage Reference Voltage 1µm Reference Voltage Start-Up • V_REC,min=2.2V 3× IRef = 3 µA IRef = 1 µA R1 Circuits 24.9 k • RRSmin = V_REC,min-V_LDO=0.7V

ICE-LAB, Aarhus University 53/57 Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Voltage Comp1 264µm/ 264µm/ Comp2 ROPOSED URST - 0.18µm 0.18µm - V_LDO Double- Pass Referece P B Regulator Pas/Act Pas/Act C IN1 Stor Neural C Current Burst MS3 MS4 LDO Recording En 290µm/ 290µm/ 77 pF Limiter Detector 0.35µm 0.35µm Front-End

DETECTION CIRCUIT IN2

• An inverter as a 1-bit ADC turns the signal at the dust terminals to rectangular signal • An edge extractor circuit makes short reset pulses according to each rising and falling edges of the generated rectangular signal • The watchdog circuit gets reset by each of the reset pulses. If it doesn’t get reset for certain time it rises a flag that shows the absence of ultrasonic power burst.

IN1 V_REC Watchdog

nA circuit 1-bit Edge extractor Circuit X ADC 200 BDO Z Y IN1 Y XOR M1 CWD X 150 fF Delay cell Z

ICE-LAB, Aarhus University 54/57 Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Voltage Comp1 264µm/ 264µm/ Comp2 - 0.18µm 0.18µm - V_LDO Double- Pass Referece Regulator Pas/Act Pas/Act C IN1 Stor Neural Current HIP HOTO MS3 MS4 CLDO En C P Burst Recording 290µm/ 290µm/ 77 pF Limiter Detector 0.35µm 0.35µm Front-End

IN2

100 100 µm 300 µm 300

300 µm

75 µm

ICE-LAB, Aarhus University 55/57 Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Voltage Comp1 264µm/ 264µm/ Comp2 - 0.18µm 0.18µm - V_LDO Double- Pass Referece Regulator Pas/Act Pas/Act C IN1 Stor Neural C Current Burst MS3 MS4 LDO Recording En ESULTS 290µm/ 290µm/ Limiter R 77 pF Detector 0.35µm 0.35µm Front-End

IN2

Start-Up V_REC Vertical stage Horizontal stages V_LDO

BD_Out

Top: transient measurement of rectified voltage (VREC), Power Amplifier Transducer Stage Controller outputvoltage of the regulator (VLDO), and the Burst DC Power Supply detector output (BDOut).Bottom: the acoustic burst Wave Absorber Hydrophone s Pre-Amp B measured by the hydrophone. Function Generator

ICE-LAB, Aarhus University 56/57 Active Rectifier V_REC On-Chip Circuits Active Diode 1 Active Diode2

+ MS1 MS2 + Voltage Comp1 264µm/ 264µm/ Comp2 - 0.18µm 0.18µm - V_LDO Double- Pass Referece Regulator Pas/Act Pas/Act C IN1 Stor Neural C Current Burst MS3 MS4 LDO Recording En 290µm/ 290µm/ 77 pF Limiter RESULTS Detector 0.35µm 0.35µm Front-End

IN2

Simulated and measured voltage conversion ratio of the proposed Simulated and measured Power Conversion Efficiency (PCE) and rectifier versus input frequency. maximum reusable power versus input frequency

ICE-LAB, Aarhus University 57/57 SUMMARY

• Brain stimulation techniques were reviewed and the importance of using optogenetics was highlighted • Different powering and communication mechanisms were reviewed • Ultrasonic approach is probably the best approach for deep implants with

ICE-LAB, Aarhus University 58/57