Thrust III: Low-Power Wearable NanosensorsÖmer OralkanDepartment of Electrical and Computer EngineeringNorth Carolina State University

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ASSIST Sensors OverviewBiochemical sensing

Cortisol, electrolytes/hydration(glucose, lactate, alcohol)

Gas/particulate sensing

Ozone, NOx, H2S, VOCs (indoor), particulate matter

Bioelectrical sensingExG, hydration

Biophotonic sensingPulse oximetry (blood pressure) Acoustic sensing

Body sounds

Nano-structured

MOx

Polymer coated MEMS

Hydrogel skin interface

Polymer coated sdAb, MIP, enzymes

COTS microphone

Optical particulate sensing

AgNWelectrodes

Hydrogels/liquid metal

Optical TX/RX

Low-power controller/radi

o

Asthma, cardiovascular health

Cardiovascular health Asthma

Stress, cardiovascular health, (tracking glucose, alcohol,

lactate; compliance monitoring)

Hydration, cardiovascular health

Future directions: Continuous glucose tracking in sweat (possibly in ISF), pharmaceutical compounds for compliance monitoring, cuffless blood pressure monitoring 3

Team and ProjectsTASK TESTBED PROJECT PI

Environmental sensing

HET 1.+/SAP 2.0 Low-Power Unheated Ozone Sensors Jackson

HET 1.+/SAP 2.0 Cross-Reactive Metal-Oxide Nanowire Sensor Array Integrated on Si CMOS using Deterministic Assembly

Mayer

HET 1.0/SAP 2.0 Design and Fabrication of Ultra-Low-Power Gas Sensors Misra/Lee

HET/SAP 2.0 Compact Particulate Sensor Muth

HET 1.+/SAP 2.0 Mechanically Resonant Chemical Sensor Arrays Based on CMUTs Oralkan

Biochemical/Bioelectric/Biophotonic

sensing

HET/SAP 2.0 Optical Methods for Biosensing Bozkurt

HET 2.0/3.0 Nano-Science and Nanotechnology Approaches for Continuous Sensing of Cortisol

Bhansali

HET 2.0/3.0 Soft Human-Device Interfaces: Flexible Hydrogel EKG Electrodes and Capillary-Osmotic Sweat Sampling

Dickey/Velev

HET 1.0/SAP 2.0 Silver Nanowire Based Wearable Sensor Systems for Skin Hydration Monitoring

Zhu

Bhansali DickeyLee Mayer Misra Muth Oralkan Velev ZhuJacksonEnvironmental Sensing Biophotonic/Biochemical/Bioelectrical Sensing

Bozkurt4

Major Accomplishments in Thrust III Demonstrated selective gas sensors based on ALD-

MOx operating at room temperature. Integrated metal-oxide coated silicon nanowires with

standard CMOS frontend circuits. Demonstrated low-power VOC sensing using CMUT

arrays with polymer functionalization. Demonstrated continuous non-invasive sweat

sampling using a hydrogel-based capillary-osmotic pump with embedded microfluidic channels.

Demonstrated multiple-use cortisol sensing using MIP-based functionalization layers.

Demonstrated skin hydration sensing using AgNW-based soft electrodes.

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Key Challenges and ASSIST Strategies in Environmental Sensing

Minimize power consumption

Isolated nanowires that can be self-heated

Room temperature sensing with MOx

Power cycling in accordance with sampling rates

Achieve required selectivity

Multidimensional functionalization

Polymers on resonator arrays

Package-level and sensor-level filters

Multiple MOx nanowires

Achieve required accuracy/reliability

Pre-calibrate sensors

Correct for long-term drift

Use differential sensing to reject CM variations

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Key Challenges and ASSIST Strategies in Biochemical/Bioelectric/Biophotonic Sensing

Minimize power consumption

Low-power custom AFEs/electro-optics

Achieve noninvasive/continuous

biosampling

Hydrogel microfluidics to transport sweat

Ensure biocompatibility

Testing at the material level

Achieve required accuracy/reliability

Standard calibration, e.g., Franz diffusion cell, moisture meter

Multiple-use cortisol (model biomarker)

sensing

Gradually exposed sdAbs and scFv

Molecularly imprinted polymers

Target a model biomarker that can be

enzymatically detected for platform

demo 7

ALD-MOx-based gas sensors operating at room temperature can selectively sense ozone

10 nm ALD SnO2

0 1000 200020000

20200

20400

20600

20800

21000

24% RH

Resis

tanc

e (Ω

)

Time (s)

Room Temperature Response to O3

0

50

100

O3 ConcentrationO

3 Con

cent

ratio

n (p

pb)

• Sensing power consumption <50 nW

• Sensor reset by UV exposure

• Projected power with 2% UV duty cycle and optimized packaging ~100 µW

0 1000 20000.0

0.2

0.4

0.6

0.8

dR/d

t (Ω

/s)

Time (s)

Rate of Resistance Change for Room Temperature O3 Exposures

0

50

100

24% RH

O3 Concentration

O3 C

once

ntra

tion

(ppb

)

O3:NO2selectivity >3:1

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Organic molecular layers can filter interfering gases at the sensor level

Glass or SiO2

GateAl2O3

ZnO

Al2O3

Glass or SiO2

GateAl2O3

ZnO

Al2O3

Indigo dye

75 nm of a thin film of Indigo dye is deposited over the ZnO TFT based sensor.

Exposed open active area: no filter

Indigo film filters O3 before reaching the ZnOinterface

180 200 220 240 260 280 300

0.970

0.975

0.980

0.985

0.990

0.995

1.000

1.005

110 ppb 170 ppb 370 ppb 550 ppb 1000 ppb

∆ I =

I D /I D0

(% C

hang

e)

VGS = 0 V, VDS = 0.5 V

Time (s)

Sensors with Indigo thin film

0 100 200 300 400 500 600 700 8000.0000

0.0001

0.0002

0.0003

0.0004

0.0005

Chan

ge in

Slo

pe -

Diffe

rent

ial

Slope Integral Fit Line

VGS = 0 V, VDS = 2 V

Ozone Content (ppb)

• Average power consumption <1 µW. • Sensor reset by UV exposure. Compatible with filter layers.• Other organic molecular layers are available. Phthalocyanine reactivity with nitrogen

dioxide is reported (Brunet J. et al, Thin Solid Films (490) 1 2005 pp.28). 9

Electric-field assisted directed assembly enables integration of MOx-NWs with CMOS

Si coreALD MOx shell

Localized regions of highest field intensity within patterned depressions provide high-yield nanowire assembly with registration to predefined features on the CMOS chip

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CMUT resonator arrays with polymer coatings can achieve low-power VOC sensing

Surface functionalization

Mechanical resonator

Electrical oscillator

Startup circuit

Nanoengineeredpolymers

Main processor

Frequency counter

Capacitive Micromachined Ultrasonic Transducer (CMUT)

10% duty cycle

Digital data

Target analyte: VOCs

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7-300

-250

-200

-150

-100

-50

0

50

Time(ms)

Am

plitu

de (m

V)

600 600.5 601 601.5 602-40

-30

-20

-10

0

10

20

30

40

Time (µs)

Am

plitu

de (m

V)

Startup time

2 3 4 5 60

1

2

3

4

5

Frequency (MHz)

Mag

nitu

de (k

Ω)

20 V20 V (Best Fit)16 V

• Vacuum Cavity: Higher Q than cantilever with an equivalent area.Easier functionalization using polymers.

• Parallelism: Multiple resonating cells in an element (Robustness)Low motional impedance.

• Array Structure: Multiple elements per array(Multi-channel capability)

77 μW when operated with 10% duty cycle from a 1.5-V supply

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0 0.5 1 1.5 2 2.5 3-4

-3

-2

-1

0

1

2

3

4

Time (mins)

Freq

uenc

y sh

ift (k

Hz)

10 ppm12 ppm14 ppm16 ppm18 ppm20 ppm

clean air toluene clean air

Gaps as small as 50 nm

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CMUT arrays with orthogonal functionalization layers and a custom AFE provide selectivity

0 0.5 1 1.5 2 2.5 3-4

-3

-2

-1

0

1

2

3

4

Time (mins)

Freq

uenc

y sh

ift (k

Hz)

10 ppm12 ppm14 ppm16 ppm18 ppm20 ppm

clean air toluene clean air

10-2 10-1 100 10110-1

100

101

102

103

104

τ (sec)

σ y(τ)

1.05 Hz

Achieved figures for toluene with PIB functionalization:Sensitivity: 270 Hz/ppm; Resolution: 10 ppb

Initially six channels: Unfunctionalized (ref.) Polyisobutylene (PIB) Polyvinyl alcohol (PVA) Polyethylene glycol (PEG) Poly allylamine hydrochloride (PAAM) Polyetherurethane (PEUT)

OSC2

AMP

FreqCounter

OSC1

MU

X

MU

X

FCLK

READ

MU

X

FCO

UNT_

TEST

CLK_

TEST

OSC

_SEL

OSC

_OUT

OSC_IN

OUT

_SER

IAL

CLK_

OUT

Parallelto

Serial

ASSIST VOC AFE IBM 0.18-μm

BiCMOSprocess.

expected < 50 μW with 10% power cycling

Digital output

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Hydrogel-based microfluidic skin interfaces can sample sweat non-invasively and continuously

This can be achieved through doping the hydrogels with electrolytic species to: Create osmotic pressure differences with the body to drive fluid flow.

Goal: Continual sweat intake for 12 hoursDrive fluid flow based on concentration gradients

created by hydrogels

Hydrogel – Osmotic and capillary forces; Ionic conduction

EGaIn – Flexible metal electrode Electrode Arrays - Sensing Reservoir- Collect fluid in hydrogel and evaporate

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Hydrogel-based microfluidic skin interfaces can sample sweat continuously

0 5 10 15 20 25 30 350

5

10

15

20

25

Length Traveled Rate

Time (Minutes)

Leng

th T

rave

led

(mm

)

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Rat

e (m

m/m

in)

Motivation

Gel 1 – Interfaces Body

Gel 2 – Absorbs Fluid at End

Rate and Distance over Time

Intake Demo

Sped up 600x

Gels with have increasing ionic strength to create a pressure difference across whole system

Microfluidic Design

Π = 𝑖𝑖𝑖𝑖𝑖𝑖Δ𝐶𝐶

Gel 1Gel 2

40-200 nL/min

Successfully used hydrogels to draw fluid through a membrane and microfluidic network

Using osmotic principles to create a pressure difference with the body to drive fluid flow into our device

Osmotic and capillary forces will drive fluid from the skin through our hydrogels and microfluidic network

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Molecularly imprinted polymer layers enable multiple-use cortisol sensors

Objective: Construction of reliable and stable biosensor for continuous monitoring of cortisol (model biomarker)

Three approaches: 1)sdAb and scFv as an alternate to conventional monoclonal antibody. 2) Increase the stability of antibodies by specific polymer coating. 3) MIP as a reusable sensing layer.

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Down to 10-pM detection demonstrated for cortisol using MIP functionalization.

Selectivity over similar competing biomolecules. Improve the stability of electrode by exploring alternative

polymers to polyimide. Copper nanoparticle synthesis for electrode improvement in

progress.

… as well as low detection limits and high selectivity

100 µM of various physiological interferents 16

This versatile biochemical sensor platform can be used to sense glucose, lactate, alcohol and other biomarkers of interest in sweat and ISF

Enzymatic reactions (glucose, lactate)

MIP (cortisol) sdAb, scFv (cortisol) Ionselective electrodes (Na, K)

Hydrogel (sweat) Microneedles + hydrogel (ISF) US xducer + hydrogel (ISF through

sonophoresis)

Sweat is easy to access and significantly correlated with blood for many target analytes of interest. 17

Self-powered pulse oximetry is feasible in wearable form factors

Pulse Oximeter (Gen-0)

Includes ASSIST supercaps

5 s every minute Continuous recording

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This approach can be implemented at lower power and be extended to blood pressure measurements

tissue-device coupling modelling

multi-junction

photodiodes

anti-reflective coating

wavelength selection

monolithic TIA

compressed sensing

Tissue LEDPhotodiode

Micro Controller

BlueTooth LE

WiFi

Accelerometer

EnergyHarvester

AFE

Visualization

Processing

Recording

System on

Chip

ECG

Pulse Ox

Chest Patch

System on Chip

Accelerometer

PulseOx Wrist Band

Accelerometer

ECG

PeripheralPulseWave

R-peak

pulse transit time

Note: Actual ASSIST gen-0 data 19

BenchmarkingSensor/Key Specifications Literature/Commercial Data ASSIST Demonstration

MOx gas sensor(temperature, sensitivity, resolution, power)

Previous thin film sensors showed detection of 50-ppb O3 with 10 mWpower consumption at 200°C [1].

Demonstrated <50-ppb resolution for O3 with 50 nW power consumption at room temperature (100 μW with UV).

Polymer coated CMUT resonatorbased gas sensor (power)

Previously 18-MHz CMUT based resonant sensor w/PIB showed 100 ppb – 1 ppm level detection limit for DMMP. Power ~80 mW [2].

Demonstrated a 4.5-MHz CMUT based sensor with 77 μW power consumption (10% duty cycle). Toluene sensingw/10-ppb resolution.

Biochemical cortisol sensor Previously electrochemical immunosensors demonstrated a LOD as low as 3.5 pg/ml for cortisol [3].

Demonstrated a LOD of 0.64 pM with Ag@ AgO–polyaniline HNC [4] and 10 pM with MIP with 6 mW power.

Skin interface Other similar devices were demonstrated for color based ion testing only [5].

First of its kind as a noninvasivepassive continuous sampling device on skin.

Pulse oximeter(Power)

Previously a thermoelectric powered 89 μW (26% duty cycle) wireless pulse ox was demonstrated [6].

Solar powered ~800 μW PPG (5 μW for optics) (8% duty cycle). With custom ASIC and SoC integration <100 μW.

Bioelectrical hydration sensor A skin patch previously showed 89%impedance change at 15 kHz for hydrated vs. dehydrated skin [7].

The AgNW electrode based sensor demonstrated 95% at 15 kHz.

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Summary of Future Directions in Thrust III

Multi-channel gas sensors combined with pattern recognition for improved selectivity.

Custom AFE integration for all sensors. Develop a complete biochemical sensing platform with sweat

as the bio-sample and glucose, lactate, and alcohol as target analytes.

Explore noninvasive sampling of subcutaneous ISF using techniques such as sonophoresis.

Multiplexed assays for multiple biomarkers. Sensing pharmaceutical compounds or added markers for

medication compliance monitoring. Custom biophotonic sensors with lower power.

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Thank you.Questions?

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References

[1] Th. Becker, L. Tomasi, Chr. Bosch-v.Braunmuhl, G. Muller, G. Sberveglieri, G. Fagli, E. Comini, “Ozone detection using low-power-consumption metal–oxide gas sensors,” Sensors and Actuators A, 74, 1999, 229–232 [2] Park, Kwan Kyu, Hyunjoo Lee, Mario Kupnik, Ömer Oralkan, Jean-Pierre Ramseyer, Hans Peter Lang, Martin Hegner, Christoph Gerber, and Butrus T. Khuri-Yakub. "Capacitive micromachined ultrasonic transducer (CMUT) as a chemical sensor for DMMP detection." Sensors and Actuators B: Chemical 160, no. 1 (2011): 1120-1127.[3] Moreno-Guzmán, María, Marcos Eguílaz, Susana Campuzano, Araceli González-Cortés, Paloma Yáñez-Sedeño, and José M. Pingarrón. "Disposable immunosensor for cortisol using functionalized magnetic particles." Analyst 135, no. 8 (2010): 1926-1933.[4] Kaushik, Ajeet, Abhay Vasudev, Sunil K. Arya, and Shekhar Bhansali. "Mediator and label free estimation of stress biomarker using electrophoretically deposited Ag@ AgO–polyaniline hybrid nanocomposite." Biosensors and Bioelectronics 50 (2013): 35-41.[5] Huang, Xian, Yuhao Liu, Kaile Chen, Woo‐Jung Shin, Ching‐Jui Lu, Gil‐Woo Kong, Dwipayan Patnaik, Sang‐Heon Lee, Jonathan Fajardo Cortes, and John A. Rogers. "Stretchable, Wireless Sensors and Functional Substrates for Epidermal Characterization of Sweat." Small (2014).[6] Torfs, Tom, Vladimir Leonov, Chris Van Hoof, and Bert Gyselinckx. "Body-heat powered autonomous pulse oximeter." In Sensors, 2006. 5th IEEE Conference on, pp. 427-430. IEEE, 2006.[7] Huang, Xian, Woon-Hong Yeo, Yuhao Liu, and John A. Rogers. "Epidermal differential impedance sensor for conformal skin hydration monitoring." Biointerphases 7, no. 1-4 (2012): 1-9.

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Literature data shows glucose levels in sweat track blood glucose levels

Epidermal contamination Evaporation of the sweat Desquamation of stratum corneum vs.

glucose in sweat.

T. C. Boysen, S. Yanagawa, F. Sato, and K. Sato, “A modified anaerobic method of sweat collection,” J. Appl. Physiol.,56:1302-1307, 1984.

J. Moyer, D. Wilson, I. Finkelshtein, B. Wong, and R. Potts “Correlation between sweat glucose and blood glucose in subjects with diabetes,” Diabetes Tech. Therap., 14:398-402, 2012.

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ISF Extraction by Sonophoresis

J. Kost, S. Mitragotri, R. A. Gabbay, M. Pishko, and R. Langer, “Transdermal monitoring of glucose and other analytes using ultrasound,” Nature Medicine, 6:347-350, 2000.

15 hours of high skin permeability after single 2-min 10-W/cm2 US application

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