Transcript
Page 1: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Integrated Circuits and Systems for Biomedical Applications

Joonsung Bae

[email protected]

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Agenda

Introduction to IMEC

Wearable Healthcare

Introduction

Analog Sensor Interface

Digital Signal Processing

Implantable Neural Interface

Introduction

ASIC Architecture

Recording / Stimulating Circuits

Spike Sorting

Joonsung Bae 2

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IMEC – Leuven, Belgium

Joonsung Bae 3

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CMOS and beyond CMOS

Joonsung Bae 4

Industry’s partner ecosystem

R&D 300mm cleanroom

Next-generation logic/memory devices

3D system integration

Advanced patterning

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Wearable

Chronic disease management

Lifestyle and preventive care

Bio-medical sensor SoC

Wearable prototypeshadware/firmware/sotware/mechanics

Joonsung Bae 5

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Life Sciences

Personalized medicine

Neuro-Electronics

DNA analysis

Single-molecule interaction

Joonsung Bae 6

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Data Science and Data Security

Data extraction

Data mining

Data visualization

Machine learning

Data security

Joonsung Bae 7

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Wearable Healthcare

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Market Trends

Joonsung Bae 9

1990s:

• PCs

2000s:

• Notebooks

2010s:

• Smartphones/Tablets

2020s:

• Wearable devices

From portable devices to wearable devices

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Growing Industry Interest

Joonsung Bae 10

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Technology Enablers for Intelligence

Joonsung Bae

Cloud computing, Big data analysis

Flexible electronics

Autonomous wireless connectivity

Advanced sensor platform

Software

Material

Protocol

Hardware

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Smart sensor

SensorPhysical property

Quantitative indication

Sensing element

Signal conditioning

Generate response

Signal processing

Electrode

Antenna

Transducer

Microphone

Photo-detector

Wireless data transmission

Actuator response

User feedback

Compression

Feature extraction

Signal analysis

security

Analog interface circuitry

Analog to Digital Conversion

12Joonsung Bae

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Sensor Hardware : SIMBAND

Joonsung Bae 13

Tizen OS

Sensors

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Cloud Sensor Platform : SAMI

Like Apple HealthKit Platform

Open API to analyze the sensed signal

Continuous and Non-invasive

Joonsung Bae 14IT대학 교수 세미나

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Challenges

Joonsung Bae 15

Long Term Battery Autonomy

High Quality and Reliable Data

Low Cost

Desirable form factor

Personalized

Many sensors

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Smart Sensor Devices

Joonsung Bae 16

Sensor interfaces

Local processing

Data collection

Comm. interface

Radio

Storage

Controller

Power management

data stream

Man

y se

nso

rs

µProcessorDSP

Memory

Accelerators

DMA

Local processing Cloud processing

Clocking

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Typical Architecture

Joonsung Bae 17

AHB

Processor

ARM, ARC

Memory

SRAM, Flash

Accelerators

Filters

Sample Rate Conversion

Encryption

Compression

Matrix/Vector calculation

FFT

Timestamp

DMA

ABP

Sensor

read-out

ECG, BioZ,

GSR, PPG, GP

Sensor drivers

LED

CS (BioZ)

Oscillator

CMUPMU

LDO, DC-DC

Interfaces

SPI, I2C, UART, GPIOTimers

RTC

Analog Digital

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Analog Sensor Interface

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Signal Characteristics

19

[Webster1992]

10mV

1mV

100uV

10uV

1uV

100nV

1Hz 10Hz 100Hz 1kHz 10kHz

ECG

Action Potentials

LFP

ECoG

EEG

EMG EMG

ECG

EEG

ECoG&

LFPAP

Joonsung Bae

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Sensing Challenges

Joonsung Bae 20

Cbo

dy-t

o-

main

s

BIASVBZbias

Zelec2

Zelec1

V2

V1

VB

MAINS

Sensor

Interface

DC-offset:

Mains interference (VCM):

Electrode Impedance Mismatch converts VCM

into VDM

21 VVVDC

BIASCCM ZIV

V V CM

ZIN

Z ZIN E2

Inherent CMRR

V V CM

ZIN

Z ZIN E1

DV

VCM=

DZ

ZIN

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General Implementation

Joonsung Bae 21

Filters PGAIA

AA

ADC Filters

sensor

signal Digital samples

#bits@sample rateOther phases / frequencies

DC Control

Application requirements

High input impedance

Low thermal noise

Low 1/f noise

Large dynamic range

Low power

High CMRR

Low offset

Design techniques

Chopper modulation

Correlated double-sampling

DC-servo

Bootstrapping

Design in weak inversion

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Digital Signal Processing

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Accelerators - Motivation

Joonsung Bae 23

A processor (like e.g., ARM Cortex M0) is popular for embedded applications

Ease of programming

Availability of tools and hardware

However:

optimized for controlling tasks.

DSP tasks (like data filters) not well supported needs many more cycles

Latency due to software (Real-time issue)

Might be less accurate

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Accelerators

Joonsung Bae 24

For sensor modules several accelerators might make sense:

Digital filtering (LPF, HPF, CIC)

Sample Rate Conversion

Motion Artefact Reduction

Time-stamping

Encryption

Compression

Vector/Matrix calculations

FFT

....

They off-load the processor and can do the calculations faster, more accurate and with less energy

Page 25: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Motion Induced Signal Artifacts

Joonsung Bae 25

Ambulatory ECG monitoring

Enabling continuous health monitoring under user’s daily routine

Body movement occurs significant Motion Artifacts on ECG signal, which suffers from ..

Poor signal quality

Potentially wrong clinical diagnosis

Steady Motion induced

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PCA Processing for Artifact Reduction

Condense Measured data set into a few “principal components”

Principal components are a linear combination of the data set, with weights chosen so that they are mutually uncorrelated

Joonsung Bae F. Castellas et. al. “Principal Component Analysis in ECG Signal Processing”

8 channelsMeasured ECG Processed ECG

4 principalcomponents

Mutuallyuncorrelated

PCAProcessing

PCA is powerful algorithm for MA reduction Because MA and ECG are uncorrelated

Page 27: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

PCA Algorithm

Measure M-channel ECGs with N-samples

Define the data matrix X

Calculate the covariance matrix Sx

Calculate the Eigenvectors and Eigenvalues of the Sx

Chose feature vector (P) with eigenvectors

Final Data = P ∙ X

Joonsung Bae F. Castellas et. al. “Principal Component Analysis in ECG Signal Processing”

Mch

an

nels

N samples

X∙XT (multiply a large matrix with its transposed matrix)

P∙X (multiply a small matrix with a large matrix)

X-E (column-wise subtraction for eigenvalue calculation)

Huge matrix operations

H/W accelerator for vector / matrix operations is needed to

reduce the burden on M0

Page 28: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Vector / Matrix Operations

Principal Component Analysis (PCA) and Independent Component Analysis (ICA) to separate any noise from ECG signal by making use of N-channel ECG signal

Joonsung Bae 28

▸ Transposed

multiplication

▸ Matrix

multiplication

▸ Matrix row

summation

Rnn = Anm . AT

mn

n = 1..4, m = 1 ... 5120

Rm =

Processor

Memory MAU accelerator

AHB

Page 29: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Matrix Processor Kernel

Joonsung Bae 29

Matrix to Matrix multiplication

Accumulator in the inner loop

Define ResultR[COUNT_2][COUNT_1];

For INDEX_1=0 to COUNT_1 -1 { // for each col (B)

For INDEX_2=0 to COUNT_2 -1 { // for each row (A)

Rval=0;

For INDEX_3=0 to COUNT_3 -1 {

Rval = Rval + (operandA[INDEX_2][INDEX_3] *

operandB[INDEX_3][INDEX_1]);

} // for each col(A) & row(B)

ResultR[INDEX_2][INDEX_1] = Rval

}

}

Pseudo code

CO

UN

T_

2

COUNT_3 COUNT_1

CO

UN

T_

3

CO

UN

T_

2

COUNT_1

Page 30: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Benefits

Joonsung Bae 30

Perform X*XT

Software realization running on the Cortex M0 vs. Matrix Processor

Page 31: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

ECG with Motion Artifact Reduction

Joonsung Bae

PCA processing with concurrent 3-lead ECG signal

3-channel ECG (512 S/s)

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SoC Implementation

Joonsung Bae 32

0.18mm CMOS

7.2 mm x 8mm

10.4MHz core clock

On-chip 192kB SRAM

Continuous data collection with analog and digital

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Future Direction

ISSCC 2017

Joonsung Bae 33

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EEG Artifact Reduction in Analog

Joonsung Bae 34

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Analog Signal Processing

Joonsung Bae 35

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Linear Transforms

Joonsung Bae 36

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Dot Product Unit

Joonsung Bae 37

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Fully Autonomous System

Acoustic Sensing and Object Recognition System

Joonsung Bae 38

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Future Directions

Joonsung Bae 39

Machine learning!! Context-aware sensing, Motion artifact, Personalization

Dedicated Hardware with M0 or

Software Implementation with upgraded core like M4

Page 40: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Implantable Neural Interface

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Central Nervous System

Joonsung Bae 41

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Neural Interface – Closed Loop

Joonsung Bae 42

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Peripheral Nervous System

Joonsung Bae 43

Sensory perception

Motor functionality

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CMOS Chip in the Nerve

Joonsung Bae 44IT대학 교수 세미나

x8 Readout Channels

x8 Readout Channels

x16 Stimulation Units

x32 Recording Pixels

Switch Matrix

x32 Recording Pixels

Dig

ita

l U

nit

500 μm

Time [ms]

Delicate surgery procedure

MultidisciplinaryCooperation

Chip designer

Processing engineer

Neural scientist

Neural surgeon

Page 45: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Where to sense in Vivo

Joonsung Bae 45

45

Electrode

Skull

Stratum Corneum

SubcutaneousLayers

Brain

Electrode

Electrode

Skin

EEGSubcutaneous

Scalp

EEG ECoG LFPAction

Potentials

Non-Invasive Invasive

Macroscopic

Microscopic

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ASIC Architectures

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System Architecture

Joonsung Bae 47

Ele

ctr

odes

Analog amplification

& filtering

A/D Signal processing

Data transmission

Data

analy

sis

Stimulation circuitry

D/A Digital control

Data transmission

How to partition the system

Page 48: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Signal Processing and Integration

Joonsung Bae 48

What to do with all

that data??

Local signal processing

Data reduction/compaction

Feature extraction

Reduced output data rate and consequently reduces TX power

But, algorithms can be easily computationally-intensive

Need trade-off between TX power vs processing power

Algorithm and hardware optimization is required

Transmission Data

Processing Power

Page 49: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Passive Arrays

Joonsung Bae 49

Integrated External

Ele

ctr

odes Analog

ampl.A/D Signal

processingData

transmission

Data

analy

sis

Stimulation circuitry

D/A Digital control

Data transmission

[Campbell et. al. 1991]

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Active Arrays

Joonsung Bae 50

[Lopez et. al. 2013, Lopez et. al. 2016, Raducanu et. al. 2016]

Integrated External

Ele

ctr

odes Analog

ampl.A/D Signal

processingData

transmission

Data

analy

sis

Stimulation circuitry

D/A Digital control

Data transmission

Page 51: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Active Arrays

Joonsung Bae 51

Target: reduce output data rates and power

Spike detection => only transmit spike data and timestamps

Spike sorting => only transmit cluster information

Lossless data compression

Other advantages:

Simple close-loop functionality

Increased number of readout channels (> 1000)

Integrated External

Ele

ctr

odes Analog

ampl.A/D Signal

processingData

transmission

Data

analy

sis

Stimulation circuitry

D/A Digital control

Data transmission

Page 52: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Wireless Active Probes

Joonsung Bae 52

Advantages:

Autonomous system => no cables

Reduced packaging effort

Reduced tissue damaged => untethered probe

Versatile freely-moving animal experiments

Challenges:

Power required for wireless transmission

Bandwidth

Integrated External

Ele

ctr

odes Analog

ampl.A/D Signal

processingData

transmission

Data

analy

sis

Stimulation circuitry

D/A Digital control

Data transmission

Page 53: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Fully Autonomous Active Probes

Joonsung Bae 53

Dream solution:

On-chip data analysis for advanced close-loop applications

Minimum data transmission: only configuration or status

Challenges:

Design of machine learning algorithms

Minimize size of integrated system

Integrated

Ele

ctr

odes Analog

ampl.A/D Signal

processing

Data

analy

sis

Stimulation circuitry

D/A Digital control

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Recording / Stimulating Circuits

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Neural Recording Circuits

Joonsung Bae 55

How to design a good neural amplifier

Recording

Electrode

Reference

Electrode

Low-Noise

Neural

Amplifier Filter

Programmable

Gain Amplifier ADC

Page 56: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Neural Amplifier Specs

Joonsung Bae 56

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Neuro-modulation

Joonsung Bae 57

Non-invasive

E.g. tENS (Transcranial Electrical Nerve Stim.)

E.g tMS (Transcranial Magnetic Stimulation)

Invasive

E.g cochlear implants

E.g. Deep Brain Stimulation

Various stimulation methods

Electrical

Optical

Chemical

Ultrasound

Page 58: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Electrical Stimulation

Joonsung Bae 58

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Electrical Stimulation

Joonsung Bae 59

IStim

Tissue

WE

CEIStim

IStimIStim

S1

S1

S2

S2

S3 S3

VSS

VDD VDD

VSS(b)

ON OFFS1

S2

S3

IStim

Tissue

WE CE

IStim

IStimIStim

S1

S1

S2

S2

VSS

VDD VDD

VSS(a)

ON OFFS1

S2

Passive charge balancing

Series capacitor to block DC current into the tissue (avoid charge buildup)

Short to ground (usually limits stimulation frequency)

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Spike Detection & Sorting

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Neural Probe Data Bottleneck

Joonsung Bae 61

Upscaling will generate ever more data.

Example:

Sampling Rate = 30kSps

Resolution = 10bits

Number of Channels = 1000

Total Data Rate = 300Mbps

What to do with all that data??

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Neural Systems

Joonsung Bae 62

Transmitting raw data over wireless is too power hungry!

Mostly wired solutions are used today

Bulky and unreliable

Impose serious limits on the experiments that can be performed

7.2 mm

20 mm

3 mm

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Spike detection

63

Raw signal

Filtering

Emphasis

Threshold

Window

Goal:

Find the regions in the raw signal

where a spike is present and

discard the rest.

Joonsung Bae

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Spike detection

64

Raw signal

Filtering

Emphasis

Threshold

Window

BPF removes undesired signals:

baseline wander

LFP

High-frequency noise

[S. Gibson 2012]

Joonsung Bae

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Spike detection

65

Raw signal

Filtering

Emphasis

Threshold

Window

Filtered data

NEO

Amplify spike for more reliable thresholding

Avoid erroneous spike detection

Several methods

Non-linear energy operator

Template matching

[S. Gibson 2012]

Joonsung Bae

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Spike detection

66

Raw signal

Filtering

Emphasis

Threshold

Window

Retain only spike signals

Significant data reduction

NEO

[S. Gibson 2012]

Joonsung Bae

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Spike alignment

Threshold crossings are typically noisy

Need to find a better way to properly align the detected spikes for efficient feature extraction and spike clustering.

Align based on local maximum

Align based on maxim slope

67

After spike detection After spike alignment

[S. Gibson 2012]

Joonsung Bae

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Spike Sorting

Joonsung Bae 68

Recorded signal = superposition of signals originating from various neurons close to the recording site.

Which neuron fires when?

Different neurons generate different spike shapes

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Spike Sorting

Joonsung Bae 69

Spike sorting:

identify spike times of individual neurons

“which neuron fires when”

Obviously reduces data rate significantly

But is also often the first step required for proper data interpretation

Neuron A

Neuron B

Neuron C

Spike sorting

Page 70: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Feature extraction

Map time-domain waveform onto multi-dimensional feature space

Simple example:

Peak-to-peak amplitude

Spike width

More complex algorithms extract much more features:

Principle Component Analysis (PCA)

Discrete Wavelet Transform (DWT)

70

AmplitudeW

idth

Joonsung Bae

Page 71: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Clustering

Identify clusters in the multi-dimensional feature space

Clusters indicate similar spikes spikes originating from the

same neuron

Very active field of ongoing research (cfr. machine learning)

71

NEURON A spikes

NEURON B spikes

NEURON C spikes

Joonsung Bae

Page 72: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Neural Signal Processing

Joonsung Bae 72

[Gibson 2012]

Page 73: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Future Directions

Joonsung Bae 73

Incredible progress, yet still such a long way to go

High-density analog

Digital signal processing

Material science & processing technology

Wireless power and data

Algorithm for efficient spike

sorting

Protocol for autonomous connectivity

Page 74: Integrated Circuits and Systems for Biomedical Applicationsysmoon/courses/2017_1/grad/12.pdf · 2017-05-30 · Integrated Circuits and Systems for Biomedical Applications ... GSR,

Any Suggestions?

배준성 (裵俊盛)

[email protected]

http://sites.google.com/view/kwbics


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