THE MEDICINE OF THE FUTURE YOU LL NEED TO TAKE ONLY ONCE, AND IT IS BIOELECTRONIC Wouter A. Serdijn, Dutch Ultra Low-Power Conference, Nijmegen, the Netherlands 2-3-2018 BIANCA SAEZ, SUFFERING FROM TOURETTE S SYNDROME https://www.youtube.com/watch?v=0opqgx6fspu 2 1
NEUROSTIMULATION 3 THE BRAIN: OUR MAINFRAME An electro-chemical machine Chemical component Cure using medicine Global effect (side effects) 19th century approach Electrical component Cure using electricity Local effect Instantaneous and reversible 21st century approach 4 2
NEUROSTIMULATION Current treatment Electrodes implanted in the brain - Suppress undesired activity - Generate therapeutic activity Wires (leads) - Connect the electrodes to the pulse generator Pulse generator in the chest - Generates electric pulses Picture courtesy of Medtronic, Inc. 5 NEUROSTIMULATION EXAMPLE https://www.youtube.com/watch?v=vlmq-mrgwqm Stimulator off Stimulator on Deep Brain Stimulation of the Subthalamic Nucleus for treatment of Parkinson s disease 6 3
NEUROSTIMULATION EXAMPLE Stimulator off Stimulator on Deep Brain Stimulation of the Subthalamic Nucleus for treatment of Parkinson s disease 7 NEUROSTIMULATORS The future Use new circuit techniques and alternative forms of stimulation to: 1. Make implants fully implantable in the head Drastically decrease their power consumption Make them flexible 2. Make impants smart Close the loop by including feedback 2 mm Miniaturization 8 4
The medicine of the future you ll need to take only once. This is not a chip! This is a flexible PCB Would it be possible to treat rheumatoid arthritis without drugs? Oddly, it appears to be possible. With a subcutaneously implanted chip, as was discovered by [Source: De Volkskrant, dd. 12/10/13] 9 THIS IS A CHIP: A 16-CHANNEL UHF NEUROSTIMULATOR IC WITH RECORD POWER EFFICIENCY 2,1 mm 1,6 mm This tiny neurostimulator IC can drive 16 stimulation channels simultaneously with an unprecedented energy efficiency. Designed by Marijn van Dongen. Support by and in collaboration with the SINs consortium 10 5
AND THIS IS A FLEXIBLE IMPLANT: ACTIVE ELECTRODE ARRAY FOR EPIDURAL SPINAL CORD STIMULATION Flexible spinal cord implant that can drive 12 electrodes in any configuration using only 3 wires and offers 25V compliance. Designed by Vasiliki Giagka. 11 CLOSING THE LOOP 1,75 mm Patent (PCT/NL2017/050061); not yet published; NWO- TTW Demonstrator Grant 2017 1,2 mm An additive companding neural recording amplifier IC that can read tiny neural signals on top of the stimulus and artefact, by Cees-Jeroen Bes, in collaboration with LUMC-ENT. Support by STW, TMSi, AB-Sys, 2BMedical and HealthTech 12 6
MOVING FORWARD 13 BIOELECTRONIC MEDICINE 14 7
2-3-2018 FEATURES OF BIOELECTRONIC MEDICINE Small: < 1 cm^3, perhaps down to 1mm^3 No or only a few discrete and bulky components Coupling capacitors, batteries, packaging material, connectors, electrodes, antennas, etc. Ultra low-power operation No titanium cans, New forms of biocompatible packaging and encapsulation No damage to the nerve cells Chronic implantation Totally secure and reliable 15 SOME QUESTIONS (I) How do we generate enough energy for the tiny implant? Thermal energy harvester (Seebeck effect)? Thermal energy harvester IC that can operate from small temperature differences and does not need any external power conversion components. Designed by Javad Dezyani (Section Bioelectronics, TU Delft) 16 8
SOME QUESTIONS (I) How do we generate enough energy for the tiny implant? Kinetic energy harvester? Piezoelectric MEMS energy harvester and (b) measured generated power for an atmospheric and vacuum packaged device with acceleration of 0.1 g and 1.0 g (picture courtesy of Imec/Holst centre) 17 SOME QUESTIONS (I) How do we generate enough energy for the tiny implant? Glucose fuel cell? Single Glucose Biofuel Cells Implanted in Rats Power Electronic Devices, by A. Zebda, S. Cosnier, J.-P. Alcaraz, M. Holzinger, A. Le Goff, C. Gondran, F. Boucher, F. Giroud, K. Gorgy, H. Lamraoui & P. Cinquin, Scientific Reports 3, Article number: 1516 (2013), doi:10.1038/srep01516 18 9
SOME QUESTIONS (I) How do we generate enough energy for the tiny implant? Modulation of an involuntary muscle and a kinetic energy harvester? A schematic illustration of the artificial cardiac pacemaking using electrical energy from the flexible PMN-PT energy harvester (credit: Geon-Tae Hwang et al./advanced Materials) 19 SOME QUESTIONS (II) Or how do we convey enough EM or US energy to the implant? How do we condense / focus the energy? Can there be an energy hub that converts EM/inductive into US, under the skin? How does the energy link stay optimal in case of fluctuating source, load and patient? The sensor, 3 millimeters long and 1 1 millimeters in cross section, attached to a nerve fiber in a rat. Once implanted, the batteryless sensor is powered and the data read out by ultrasound. (UC Berkeley News, August 3, 2016. Photo: Ryan Neely) 20 10
SOME SOLUTIONS 21 1 ST APPROACH: OPTIMAL NON-50K MATCH (1) An optimal non-50k antenna-electronics interface Antenna & rectifier form a high-q resonating network Large passive voltage boost increases rectifier sensitivity Choose rectifier topology with minimum resistance The 50Ω Mafia 22 11
ANTENNA-IC CO-DESIGN Antenna impedance of 10+j400 K at 900 MHz JSSC 2014; TCAS-II 15; VLSI 13; ISCAS 12 Design challenges: Highly reactive (high Q) Difficult to measure Antenna-IC co-design Designed by Mark Stoopman. Support by the Holst Centre 23 2 ND APPROACH: SPLIT POWER PATH AND SWITCHING CONTROL (1) 24 12
ECG SENSOR: BLOCK DIAGRAM 25 ANALOG ECG MONITORING PRINCIPLE: LEVEL- CROSSING ADC Processes the signal in time domain rather than magnitude domain 26 13
AN AUTONOMOUS WIRELESS SENSOR NODE FOR ECG MONITORING T-BioCAS 16, T-BioCAS 14; ESSCIRC 14; BioCAS 14; TCAS-I 13 This tiny chip (left) when mounted on a printed circuit board (middle) with electrodes and antennas becomes a batteryless ECG tag allowing the readout and wireless transmission of cardiac signals. Designed by Andre Mansano and Yongjia Li. Support by CNPq and CSC 27 COMPARISON WITH STATE OF THE ART This Work ISSCC'10 [1] ISSCC'10 [2] ESSCIRC 13 [3] ISSCC'12 [4] Sensor Signal ECG Neural EEG, EMG ECG ECG, EEG, EMG Power Source RF RF RF Battery RF/Thermal RF Source (dbm) -13 (@13.56MHz) -8-12 n.a. -10 Supply Voltage, V DC (V) 1.25 0.8 1.8 1.2/3 1.35 No. of Analog Channel(s) 1 1 1 1 4 ADC Resolution (bits) 8 8 8 12 8 Frequency Channels (MHz) 13.56/402 1 915 900 13.56 2 402/433 Data rate (kb/s) 90 3 150-800 Up to 500 4 424 200 External Components 1 TX Inductor n.a. Storage Capacitor 1 Crystal, NFC- IC, Battery 2 Crystals, Storage Cap., TX Inductor Total Power (µw) 9.7 20 16.6 18.24 19 Power Distribution 1-Ch. AFE, 8-bit ADC, PE & TX 1-AFE, 8-bit ADC, Logic TX & RX 1-AFE, 8-bit ADC, Logic & TX AFE, 12-bit ADC, MCU, SRAM & FeRAM 1-Ch. AFE, 8-bit ADC, DSP, 0.013% Duty Cycled TX Modulation (TX) OOK OOK ASK ASK BFSK Area (mm 2 ) 1.9x2.0 0.96x1.6 2.0 6.9x6.9 3.3x2.5 Technology, CMOS (µm) 0.18 0.13 0.13 0.13 0.13 1 Multi-band/multi-channel allows for simultaneous energy harvesting and transmission. 2 Off-chip NFC IC; 3 Compressed data at the output of the LC-ADC; 4 Gen2 standard. 28 14
NO COUPLING CAPACITORS Not safe (electrolysis) and there are better ways to prevent single-fault failures Bulky van Dongen, Serdijn: Does a coupling capacitor enhance the charge balance during neural stimulation? An empirical study, Medical & Biological Engineering & Computing, 2015, doi: 10.1007/s11517-015-1312-9 29 SINGLE (LOW) VOLTAGE DOMAIN (1) Stimulate using UHF current pulses and build up charge in the tissue without voltage compliance limitations Neural recording on top of stimulus and artefact, beyond the supply and tissue voltage 1. van Dongen and Serdijn: A Power-Efficient Multichannel Neural Stimulator Using High-Frequency Pulsed Excitation From an Unfiltered Dynamic Supply, IEEE Transactions on Biomedical Circuits and Systems, DOI: 10.1109/TBCAS.2014.2363736 2. Bes, Lotfi, Serdijn: Analog to Digital Data Converter, Patent (PCT/NL2017/050061) 30 15
SINGLE (LOW) VOLTAGE DOMAIN (2) Stimulate using UHF current pulses and build up charge in the tissue without voltage compliance limitations Neural recording on top of stimulus and artefact, beyond the supply and tissue voltage 2,1 mm 1,75 mm 1,6 mm 1,2 mm 1. van Dongen and Serdijn: A Power-Efficient Multichannel Neural Stimulator Using High-Frequency Pulsed Excitation From an Unfiltered Dynamic Supply, IEEE Transactions on Biomedical Circuits and Systems, DOI: 10.1109/TBCAS.2014.2363736 2. Bes, Lotfi, Serdijn: Analog to Digital Data Converter, Patent (PCT/NL2017/050061) 31 SAFETY AND SECURITY Reliable communication between parametric reader (Rp) and implant in case of emergency Robert Seepers: Implantable Medical Devices -- device security and emergency access, PhD thesis, ErasmusMC, the Netherlands, Nov. 2016 32 16
WHERE IT ALL MAY LEAD TO 33 MEDICAL IMPACT PERIPHERAL NERVOUS SYSTEM Pudendal nerve Stimulation Incontinence [Reference: Kevin J. Tracey: Electronic Medicine Fights Disease -- Stimulation of the nervous system could replace drugs for inflammatory and autoimmune conditions, Scientific American, March 2015] 34 17
MEDICAL IMPACT SENSES AND CENTRAL NERVOUS SYSTEM Restore hearing (cochlear implant) Restore sense of balance (vestibular implant) Restore sight (retinal implant) Restore smell and taste (olfactory implant) Better understanding of the central nervous system Better treatment of pain (spinal cord implant) Better understanding of the brain Better brain-machine interfaces 35 MEDICAL IMPACT THE BRAIN Better treatment of brain disorders Better treat tinnitus and auditory hallucinations, Better treat addictions (a.o. alcoholism), Better treat essential tremor, Parkinson, dystonia Better treat urge incontinence, Better treat migraine, cluster headaches and other forms of headache Better treat psychoneuroimmunological disorders Better treat chronic, phantom and neuropathic pain, Better treat depression, mania Better treat OCD spectrum disorders Better treat PTSD and anxiety Better treat schizophrenia Better treat epilepsy Treat autism, Treat dementia, including Alzheimer s disease Treat Tourette s syndrome, minimally conscious state (MCS) after traumatic brain injury, obesity, anorexia [Reference: C.O. Oluigbo, A.R. Recai, Addressing Neurological Disorders With Neuromodulation, IEEE Transactions on Biomedical Engineering, Vol. 58, No. 7, July 2011] 36 18
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