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14 January 2011

Today’s implantable stimulator market and prospective

•  Worldwide, more than 500,000 permanent cardiac pacemakers are implanted each year. As the population ages and as indications for pacemakers expand, the number of implants continues to increase.

•  Approximately 100,000 people worldwide have received cochlear implants, with recipients split almost evenly between children and adults. The vast majority are in developed countries due to the high cost of the device, surgery and post-implantation therapy. A small percentage of CI-recipients have bilateral implants, or one CI in each cochlea. Bilateral cochlear implants are a growing trend globally.

•  Statistics for all other devices, are not available at this time, but there are many patients who received neuromuscular prostheses for DBS (Parkinson, epilepsy, depression, etc), artificial retina, respiration, motor (standing up, walking, foot drop), etc…

Overview

•  Auditory system: Cochlear implant •  Visual system: Visual stimulator (visual prosthesis: cortical, retinal, etc) •  Central nervous system: Stimulators (DBS, Parkinson, epilepsy), multi-

channel sensors, closed loop prosthesis •  Vagus / Vacal nerve: Control and sensing inside the body •  Peripheral nervous systems: Various neuromuscular stimulators

(bladder, bowl, foot drop, pain, paralysis, etc..) •  Cardiovascular system: Cardiac pacemaker, defibrillator, ECG sensors •  Gastrointestinal system: Ingestible sensors and stimulators •  Respiratory system: EMG and pressure sensors •  Movement disorders: Functional electrical stimulation.

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Cochlear implants

•  “The first and, so far, most successful brain-machine interfaces (BMI)” •  It is estimated that 27 million Americans have a significant hearing

loss •  About 1 million have a severe to profound loss that would qualify for a

CI, but only 20,000 Americans have CI (2004) •  About 45,000 children are eligible but only 9,000 have CIs •  Worldwide, over 100,000 patients from age 1 to 80 years old have

received implants (2005) •  Miss America of 1995, Heather Whitestone, deaf since infancy

received an implant in 2002. •  Cost of CI ~$60,000 each; Medicare can pay around $20K; some

insurance companies may pay the rest, others will not •  Surprisingly, perhaps, the most resistance to implants comes from the

deaf community.

Advanced Bionics (Harmony) http://www.bionicear.com/

•  Power and size reduction by minimizing digital stages.

•  Aim was to offer improved aesthetics, reduction of practical limitations and improved perception.

•  Advanced signal processing and circuit techniques.

Integrated circuit for a cochlear implant, by Georgiou & Toumazou

Cochlear implants

Cochlear implants: spectral resolution (number of channels)

http://www.isvr.soton.ac.uk/soecic/simulations.html

•  The limited number of channels affects pitch perception

•  It is not possible to say for sure what a cochlear implant sounds like, and it differs from person to person. Number of channels (flexibility) play important role.

Auria Processor - Advanced Bionics

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Retinal implant

Weiland & Humayun, “A biomimetic retinal stimulating array,” EMB. Mag., 2005.

•  Blindness due to light-sensing cell malfunction is addressed by retinal implants.

•  The retinal prosthesis is designed to take over the function of the lost photoreceptors by electrically stimulating the remaining healthy cells of the retina.

•  A retinal prosthesis can be placed either on the inner retinal surface ("epi-retinal") or below the retina in the area of damaged photoreceptors ("sub-retinal") to try to stimulate the remaining viable retinal cells.

•  Electrical stimulation of the retinal cells evokes the sensation of discrete points of light (referred to as “phosphenes").

Illinois Institute of Technology

Cortical stimulator: Visual prosthesis

•  The cortical approach incorporates a microelectrode array, which is placed either intracortically or on the cortical surface. By stimulating the visual cortex directly, this approach bypasses the retina and optic nerve.

•  The Utah silicon micromachined microelectrode array. It has a large number of 1.5mm long electrodes that project out from a very thin (0.2 mm) substrate and that are separated from each other by 0.4 mm.

http://www.iit.edu/~npr/intro.html

Utah visual neuroprosthesis

http://www.bioen.utah.edu/cni/projects/blindness.htm

Cortical stimulator and neural recording Microsystems

Wise & Najafi, University of Michigan, Ann Arbor, 2004

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Neural recording Microsystems

Ying Yao et al., “A Microassembled Low-Profile 3D Microelectrode Array…,” MEMS Systems, Vol.16, 2007.

The fabricated device

Neural recording Microsystems

The multi-channel IC and a zoom on the digital FSK

transceiver.

Harrison et al., "A Low-Power IC for a Wireless 100-Electrode ….," IEEE JSSC, Vol. 42 2007.

•  Polystim multi-channel multi-chip neural interface. The ICs implementing the active part are stacked and bonded on the base of a micromachined stainless-steel microelectrodes array.

Gosselin et al. "A Mixed-Signal Multi-Chip..," TBioCAS, In press

Multi-chip multi-channel neural interface

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Chip on board setup to test the stacked ICs

•  Microphotograph showing the chip on board assembly used to test the neural interface according to the targeted multi-chip stacked configuration. The PCB uses a soft gold finish for direct bonding with gold bonding wires.

•  SEM photograph of the stacked and wirebonded ICs on the test board. The two ICs are stacked and wire bonded on a test PCB. A silicon spacer is used between the stacked ICs.

Gosselin et al. "A Mixed-Signal Multi-Chip Neural..," IEEE TBioCAS, In press

Brain machine interfaces

Nicolelis, "Brain-machine interfaces to restore motor …," Nat Rev Neuro, v4, 2003. Lebedev & Nicolelis, "Brain-machine interfaces: past,..," Trends Neur, v29, 2006.

Deep brain and cortical timlation

•  Neurostimulation can treat movement and affective disorders such as chronic pain, Parkinson’s disease, tremor, dystonia, and major depression .

•  A “brain pacemaker” is implanted to electrically stimulate specific region of the brain.

•  DBS in select brain regions has provided remarkable therapeutic benefits for otherwise treatment-resistant disorders.

www.nature.com/clinicalpractice/neuro http://www.medtronic.com

•  Several types of electrode arrays !  Thin electrode rods !  Subdural electrode grid.

Depth electrode and implantable stimulator used for DBS

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Approaches to vagus nerve stimulation

!  It is the only nerve that starts in the brainstem and extends down below the head, to the neck, chest and abdomen, where it contributes to the innervation of the viscera. Besides output to the various organs in the body, the VN conveys sensory information about the state of the body's organs to the central nervous system.

•  Implantable stimulator !  Helix cuff interface !  VNS periodic, or manual !  Not yet fully understood how VNS works !  Battery needs changing after 6 years !  Partially successful and potential for improvement.

http://www.wired.com/images/article/full/2007/05/vagus.jpg

Implantable cardiac pacemakers and defibrillators

•  A pacemaker is used to treat bradycardia (the heart beats too slowly) or arrhythmias (abnormal cardicac rhythms).

•  Types of pacemakers: !  Single-Chambered Pacemakers: Use only one lead

placed into the right upper chamber of the heart (right atrium) or the right lower chamber (right ventricle).

!  Dual-Chambered Pacemakers: Use two leads. One is placed in the right atrium, the other in the right ventricle.

!  Cardiac Resynchronization Therapy : Use three leads. One is in the right atrium, one is in the right ventricle, and one is placed through the heart’s veins to left ventricle.

!  Rate-Responsive Pacemakers: can be programmed to increase or decrease heart rate to match patient’s activities (i.e. resting or walking).

Battery ICs/Die Stack

Activity Sensor

Feedthrough

IPG

Lead

Anode

Cathode

Current State-of-the-Art of the Single and Dual Chamber Pacemaker. Medtronic,

Spinal cord stimulation

•  Chronic pain in back & legs

•  Neurostimulators work by sending mild electrical impulses to the epidural space near the spine.

•  These impulses replace pain with a tingling sensation (must be above the level of pain).

•  For Complex Regional Pain Syndrome, a chronic pain condition that most often affects the arms, legs, hands, or feet. This condition is also known as reflex sympathetic dystrophy or causalgia.

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Gastrointestinal remote sensor

•  A microelectronic “pill” for in situ studies of the gastro-intestinal tract.

•  Combines microsensors and integrated circuits with system-level integration technology.

•  The measurement parameters include real-time remote recording of temperature, pH, conductivity, and dissolved oxygen.

•  The unit comprises an outer biocompatible capsule encasing four microsensors, a control chip, a discrete component radio transmitter, and two silver oxide battery cells.

Johannessen et al. “Implementation of Multichannel Sensors for …,” IEEE TBME, V51,

Photograph of the 4.75 x 4.75

mm ASIC control chip used in the

pill. The prototype is 16 x 55 mm.

Gastrointestinal implantable devices

•  Gastric Electrical Stimulation for Gastroparesis

•  Gastroparesis is a stomach disorder in which food is digested more slowly than normal. With gastroparesis, the stomach muscles work poorly (or not at all), thus preventing the stomach from emptying properly.

•  The Enterra® neurostimulator from Medtronic received humanitarian device exemption (HDE) approval from the FDA in 2000.

•  Humanitarian Device: The effectiveness of this device for this use has not been demonstrated.

http://www3.imperial.ac.uk/biomedeng/research/bionics

Chemical sensors

•  Chemical sensors are used for identification and quantification. They need to be both selective and sensitive to a desired target species in a mixture of chemical species.

•  Types of chemical composition measurement techniques: •  Electrochemical - Basic Concepts and Definitions,

Voltammetry, Potentiometry, Conductometry, Coulometry •  Thermal - Thermogravimetry, Thermometric Titrimetry,

Thermomechanical Analysis, Differential Thermal Analysis and Differential Scanning, Calorimetry

•  Kinetic Methods - Catalytic Reactions, Noncatalytic Reactions (involve the measurement of chemical reactions or processes in a time-dependent manner)

•  Chromatography - Gas Chromatography, Liquid Chromatography, Hyphenated Techniques.

Fraden, Handbook of Modern Sensors: Physics, Designs, .., Springer, 2003.

Configuration of an optical CO2 sensor.

Liquid ChemFET construction.

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•  Purpose: !  Detect abnormal functioning !  Extract respiratory

parameters for diagnosis purposes

•  Type of sensors used: !  Myoelectric sensor:

electrical activity of respiratory muscles

!  Pressure sensor: measure the pressure and volume of gas in lungs

!  Gas and other chemical sensors: measure concentration of gas in lungs.

Sensors & actuators (catheters & wireless devices)

The respiratory system : Polystim Lab.

•  Purpose: •  Selective stimulation to improve voiding:

•  HF stimuli for somatic fibres which innervate the sphincter. •  LF stimuli for parasympathetic fibres which innervate the detrusor

•  Permanent LF stimulation using low amplitude train waveform to: •  Prevent the bladder hyperreflexia •  Maintain the bladder shape.

The bladder controller : Polystim Lab.

Amp

PW

1/Freq

Bladder

Bipolar cuff electrode

Dual- stimulator RF emitter

Data

Skin

Power

User interface

Motor prostheses

•  Neuromuscular Stimulation for Control of Limb Movement •  Close-loop control with associated sensors.

Bronzino, Biomedical Engineering Fundamentals, CRC, 2006.

Images from 4-channel FES gait

sequence performed at MIT in 1990. Subject bracing to stand,

Standing under FES control with

computer controlled

stimulator on the far left.