ISSCC 2004 / SESSION 12 / BIOMICROSYSTEMS / 12.1

12.1 Retinal Prosthesis

Wentai Liu1, Mark S. Humayun2

1University of California, Santa Cruz, CA2University of Southern California, Los Angeles, CA

Retinitis Pigmentosa (RP) and Age-Related Macula Degeneration(AMD) are incurable retinal diseases that result in profound visionloss due to degeneration of the light sensing photoreceptor cells.Retinal prostheses based on epiretinal and subretinal implants torestore useful eyesight for RP and AMD patients have been pro-posed [1], [2]. In epiretinal prosthesis, the prosthetic device isattached to the inner retinal surface while a subretinal prosthesisplaces the implant in a space between neurosensory retina and reti-nal pigment epithelium. In both methods, retinal neurons are elec-trically stimulated which bypasses the damaged photoreceptorsthereby creating visual excitation. Figure 12.1.1 shows the epi-reti-nal prosthesis described in this paper. Visual data and power, RFencoded by the extraocular unit, are transmitted inductively to theintraocular unit which in turn recovers the data/power and sets thecharge balanced bi-phasic stimulation currents for the retina viaelectrodes.

Replacement of the function of more than 100 million photore-ceptors by an electronic device within the confines of a one-inchmobile organ is a formidable challenge. Psycho-physics studiesshow that 32x32 pixels are needed to provide a useful vision(reading, facial recognition, and independent mobility) for theblind. It is necessary to accommodate about 1000-pixel driverson a chip within less than 5x5mm2. A charge balanced biphasicstimulus pattern as shown in Fig. 12.1.2 is needed for the stim-ulation of the implant electrodes at the rate of 50-100Hz toensure non-flicker vision. A total power of 250mW is required bythe intraocular unit and an encoded data stream of stimulusparameters and control information at a rate of 2Mb/s musttransmitted across the air-eye interface. A reverse telemetry of 3-5kb/s is required to transmit of the status and physiologicalinformation of the implant. The intraocular unit should be care-fully anchored and be biocompatible, hermetically sealed in acapsule made of material such as ceramic. The fixation of theelectrode array on the retina surface is done by surgical tacks.

Figure 12.1.3 is a block diagram of the power and data telemetryunit. A class E driver is used owing to its high efficiency, and abil-ity to generate high field strength with low dc voltage. The sec-ondary coil is resonated at the operational frequency of 1MHz.The shunt and series voltage regulators generate a dual rail sup-ply of ±7V for the stimulators, and 3V for the digital logic. Thereverse telemetry, based upon load modulation technique, oper-ates at 3.5kb/s by disconnecting the load for short periods. Thereverse data is detected by an envelope detector sensing the dif-ferential coupling current through the primary power coil. ThePWM waveform sent at the secondary is re-created using a dif-ferential amplifier and toggle FF with hysteresis. An NRZ datais then extracted from the PWM. A DC-DC converter functions asa closed loop power control unit. Unlike the conventional powerlinks delivering a constant power under all conditions [3], thisensures optimum power delivery by counteracting load varia-tions and coil misalignments communicated by the reversetelemetry. The forward data link operates at 2 Mb/s usingDBPSK modulation with a 16MHz carrier. It is should be notedthat the data link operates independently of the power link witha separate set of coils which allows optimizing both links simul-taneously. The interference from the power link is minimized byrelative positioning of the power and data coils accompanied byfiltering.

A microstimulator for the retinal prosthesis must be able to pro-vide programmable, but charge balanced bi-phasic waveforms interms of amplitude, width, and inter-phase intervals. Figure12.1.4 shows a microphotograph and the specifications of amicrostimulator (Retina- 3.55) which is one of the ICs designedby this group for this application. It is used for the second gener-ation of chronic retinal implant. It has 60 independent channelseach fed by two current mode DACs and is capable of generatinga variety of bi-phasic waveforms via eight profile generators forstimulus patterns. Figure 12.1.2 shows the various measuredstimulus waveforms with an amplitude of 600uA passingthrough a 10kΩ, the nominal impedance of the implant elec-trode. The current mode DACs are replaced by a multi-bias DACoccupying lesser area [4]. Several features have been added inthe latest test chip, Retina-5. The output driver circuitry isshown in Fig. 12.1.5 and uses active feedback current mirrors(A1, A2) operating with a low headroom of 0.5V to reduce thesupply voltage. Thus, the device reliability is likely increased. Byusing 1:8 demultiplexing embedded in the output stage (SW1-SW16), one driver stimulates eight electrodes. Individual driversare programmable using the gain control (M1-M60) to meet thedifferent stimulation requirements for different patients andregions of the retina.

Over a decade, in the operating room, acute tests of pattern elec-trical stimulation of retinas with a 25 element electrode array inhuman volunteers, blind due to photoreceptor loss has resultedin the volunteers able to recognize letters and crude forms suchas a box [1]. Three permanent implants, each with a first gener-ation 4x4 electrode prosthetic device (Fig.12.1. 6), conducted atthe Doheny Eye Institute in 2002-2003, indicate great promise inachieving useful vision for RP/AMD patients [5]. The patientsare able to read a large letter, count objects, recognize and differ-entiate objects such as cup from plate. Many insights inimplantable microelectronics are gained through experiments onanimal and human subjects. Given the rapidly growingmicro/nanotechnology, low power SoC, packaging and the sym-biosis between engineering and medicine, the development of thenext generation of fully integrated, but miniaturizedimplantable retinal prosthetic systems is very promising.

Acknowledgements:The authors acknowledge the contributions of the Retinal Prosthesis teamat UCSC, NCSU, and USC. This work was partially supported by NSF,NIH, and DOE.

References:[1] M. S. Humayun, E. de Juan, J. Weiland, et al., “Pattern ElectricalStimulation of the Human Retina,” Vision Research, pp. 2569-2576, 1999.[2] E. Zrenner et al., “Can Subretinal Microphotodiodes SuccessfullyReplace Degenerated Photoreceptors?” Vision Research, pp. 2555-2567,1999.[3] M. Ghovanloo, K. Beach, K. D. Wise, K. Najafi, “A BiCMOS WirelessInterface Chip for Micromachined Stimulating Microprobes,” 2nd AnnualInt. IEEE-EMB Special Topic Conf. on Microtechnologies in Medicine AndBiology, May 2002.[4] S. C. DeMarco, W. Liu, M. Humayun, and J. Weiland, “A Multi-BiasDAC for Use in Neuro-Stimulators,” IEEE J. Solid State Circuits, vol. 38,pp. 1679-1690, Oct. 2003.[5] M. Humayun et al., “Chronically Implanted Intraocular RetinalProsthesis in Two Blind Subjects,” ARVO Annual Meeting, April 2003.[6] W. Liu et al., “A Neuro-Stimulus Chip with Telemetry Unit for RetinalProsthetic Device,” IEEE J. Solid State Circuits, vol. 35, pp. 1487-1497,Oct. 2000.

• 2004 IEEE International Solid-State Circuits Conference 0-7803-8267-6/04 ©2004 IEEE

ISSCC 2004 / February 17, 2004 / Salon 1-6 / 1:30 PM

Figure 12.1.1: Conceptual diagram of the retinal prosthesis. Figure 12.1.2: Biphasic stimulus patterns.

Figure 12.1.3: System architecture of telemetry unit.

Figure 12.1.5: Output driver circuitry of retina-5.

Figure 12.1.4: Retina 3.55.

9.33%Supply sensitivity

7.24%Anodic / Cathodic tracking

0.8085Cathodic current nonlinearity (INL)

0.8224Anodic current nonlinearity (INL)

50mWPower consumption

4clock cycles (1/256 of frame time)

Timing resolution

4-bits, 3 full scale settingsAmplitude Resolution

1024 bitsFrame size

1465 frames/secMaximum frame rate

1.5MHzMaximum clock rate

60Number of channels

60Number of current generators

5.5mm x 5.25mmDie Size

1.2um CMOSTechnology

Figure 3: Retina 3.55

_+

DAC

gnd

Vss

Vnbias

Output1

+ _

Vdd

Vpbias

Anodic section

Cathodic section

Vss

Output 2 Output 8

AnodicCtrl

CathodicCtrl

A2

A1

SW9 SW10 SW16

SW8SW2SW1

M1 M30

M31 M60

Figure 12.1.6: Prosthesis with an implanted 4x4 electrode array (theprototype photo is provided by Second Sight LLC).

• 2004 IEEE International Solid-State Circuits Conference 0-7803-8267-6/04 ©2004 IEEE

• 2004 IEEE International Solid-State Circuits Conference 0-7803-8267-6/04 ©2004 IEEE

Figure 12.1.1: Conceptual diagram of the retinal prosthesis.

• 2004 IEEE International Solid-State Circuits Conference 0-7803-8267-6/04 ©2004 IEEE

Figure 12.1.2: Biphasic stimulus patterns.

• 2004 IEEE International Solid-State Circuits Conference 0-7803-8267-6/04 ©2004 IEEE

Figure 12.1.3: System architecture of telemetry unit.

• 2004 IEEE International Solid-State Circuits Conference 0-7803-8267-6/04 ©2004 IEEE

Figure 12.1.4: Retina 3.55.

9.33%Supply sensitivity

7.24%Anodic / Cathodic tracking

0.8085Cathodic current nonlinearity (INL)

0.8224Anodic current nonlinearity (INL)

50mWPower consumption

4clock cycles (1/256 of frame time)

Timing resolution

4-bits, 3 full scale settingsAmplitude Resolution

1024 bitsFrame size

1465 frames/secMaximum frame rate

1.5MHzMaximum clock rate

60Number of channels

60Number of current generators

5.5mm x 5.25mmDie Size

1.2um CMOSTechnology

Figure 3: Retina 3.55

• 2004 IEEE International Solid-State Circuits Conference 0-7803-8267-6/04 ©2004 IEEE

Figure 12.1.5: Output driver circuitry of retina-5.

_+

DAC

gnd

Vss

Vnbias

Output1

+ _

Vdd

Vpbias

Anodic section

Cathodic section

Vss

Output 2 Output 8

AnodicCtrl

CathodicCtrl

A2

A1

SW9 SW10 SW16

SW8SW2SW1

M1 M30

M31 M60

• 2004 IEEE International Solid-State Circuits Conference 0-7803-8267-6/04 ©2004 IEEE

Figure 12.1.6: Prosthesis with an implanted 4x4 electrode array (the prototype photo is provided by Second Sight LLC).