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Wearable Biosensors for Personalized Health Monitoring Wei Gao Assistant Professor of Medical Engineering Division of Engineering & Applied Science California Institute of Technology

Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

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Page 1: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Wearable Biosensors for Personalized Health Monitoring

Wei Gao

Assistant Professor of Medical EngineeringDivision of Engineering & Applied Science

California Institute of Technology

Page 2: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Wearable Biosensors for Personalized Medicine

Commercial health monitors can mainly trackphysical activities and vital signs

Challenges and opportunities: physiological monitoring at molecular levels

Page 3: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Human Sweat

Electrolytes• Na+, Cl-, K+, NH4+, Ca2+, H+

Metabolites• Lactate, glucose, urea, uric acid,creatinine

Small Molecules• Amino acids, cortisol, DHEA

Proteins & Peptides• Interleukins, tumor necrosis factor,neuropeptides

Xenobiotics• Heavy metals such as Cu, Hg, Cd,Zn, Pb, As, Ni

• Ethanol• Drugs• Cosmetics

Page 4: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

The Current Healthcare Applications of Sweat Test

Current sweat test cannot provide real time information and requires extensive laboratory analysis

Page 5: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Wearable Sweat Analysis

Nature electronics, 2018

Real time, non-invasive, continuous health monitoring

Page 6: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Fully Integrated Wearable Sensors or Perspiration Analysis

Gao et al. Nature, 2016, 529, 509.

• Real time in situ monitoring:• Metabolites (glucose, lactate)• Electrolytes (Na+,K+)• Skin temperature.

• On site signal conditioning,processing, wireless transmission.

• Real time sensor reading calibration.

• Data display on cell phone.

• Data aggregation on cloud server.

‘Smart Wristband’

wireless flexible PCB

flexible sensor array

Page 7: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Wearable Sweat Biosensors: System Level Integration

The platform consists of disposable sensor patch and reusable flexible printed circuit board.

Gao et al. Nature, 2016, 529, 509.

The selection of targeted biomarkers• Metabolites (glucose, lactate)• Electrolytes (Na+,K+)• Skin temperature.

Page 8: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

System Level Technology Development - I Flexible Sensors – Enzymatic Sensors (Glucose and Lactate Sensing)

Lactate Sensors

Reference & Counter

CNT+Chitosan

Au

Ag/AgCl

Prussian Blue

CNT+ChitosanLactate Oxidase

e-

Electrode

PB (OX)PB (Red)

GOx (OX)GOx (Red)

Gluconic AcidGlucose

Electrode

PB (OX)PB (Red)

LOx (OX)LOx (Red)

PyruvateLactate

Glucose Sensors

AuPrussian Blue

GOx+CNT+Chitosan

e-

PETPET

Prussian Blue is used as mediator to lower the operation potential(from 0.6~0.7 V to ~0 V) and minimize the interferences.

Page 9: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

System Level Technology Development - I Flexible Sensors – Ion Selective Sensors (Na+ and K+ Sensing)

Valinomycin - K ionophore

Metal ion is encapsulated in a molecular cavity whose size is matched to the ion size

According to Nernst Equation:

charge of ion Ion activity/concentration

Na ISE

K ISE

RPVB

Na ionophore X+NaTFPB+DOS+PVCPEDOT:PSS

Au

Valinomycin+NaTPB+DOS+PVCPEDOT:PSS

Au

PVB+NaCl+CNT HydrophobicAg/AgCl

Page 10: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

System Level Technology Development - IIFlexible Printed Circuit Board

ADC (built-in)

Phone User Interface

Differential Amplifier (6)

Voltage Buffer (5)

Differential Amplifier (6)

Voltage Buffer (8)

Low-Pass Filter (7)

Low-Pass Filter (9)

Microcontroller (10)

Cloud Servers

Transimpedance Amplifier (1)

Transimpedance Amplifier (3)

Inverter (1) Inverter (3)

Low-Pass Filter (2)

Low-Pass Filter (4)

Voltage Divider

Bluetooth Transceiver (11)

IGlucose ILactate RTemperature VSodium VRef VPotassiumAg/AgCl

Page 11: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Fabrication process flow for the flexible sensors

PETAu

AgAgCl

a Au patterningb

Parylene depositioncO2 plasma etchingd

Ag patterninge Ag chloridationf

gh Flexible arraySensors modification

PET cleaning

Parylene

Nature, 2016, 529, 509.

Page 12: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Characterization of the sensors

All the sensors show linear response vs concentration or logarithm of concentration

0.16

0.18

0.20

0.22

0.24

0.26

0.28

0 15 30 45 60 75 90

Pote

ntia

l (V)

Time (s)

32 mM

16 mM

8 mM

4 mM

2 mM

1 mM

150200250300

0 0.5 1 1.5 2Pote

ntia

l(m

V)

log10([K+], (mM))

[K+]

0.15

0.2

0.25

0.3

0 0.5 1 1.5 2

Pot

entia

l (V

)

log10([K+], (mM))

0.24

0.26

0.28

0.30

0.32

0.34

0 15 30 45 60 75

Pote

ntia

l (V)

Time (s)

160 mM

80 mM

40 mM

20 mM

10 mM[Na+]

210260310360

1 1.5 2 2.5Pot

entia

l(m

V)

log10([Na+], (mM))

0.21

0.26

0.31

0.36

1 1.5 2 2.5

Pot

entia

l (V

)

log10([Na+], (mM))

-6.0

-5.0

-4.0

-3.0

-2.0

-1.0

0 30 60 90 120 150

Cur

rent

(μA)

Time (s)

-6-4-2

0 10 20 30Cur

rent

(µA

)

[lactate] (mM)

[lactate]

5 mM

10 mM

15 mM

20 mM

25 mM

-600

-500

-400

-300

-200

-100

0

100

0 60 120 180 240 300

Cur

rent

(nA)

Time (s)

-600-400-200

0

0 100 200 300Cur

rent

(nA

)

[glucose] (µM)

[glucose]

100 μM

150 μM

200 μM

50 μM

0 μM

Page 13: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

System Level Interference & Temperature Compensation

Gao et al. Nature, 2016, 529, 509.

Temperature dependence

a c d b

e g h f

-600

-500

-400

-300

-200

-100

0

100

0 60 120 180 240 300

Cur

rent

(nA

)

Time (s)

-600 -400 -200

0

0 100 200 300 Cur

rent

(nA

)

[glucose] (µM)

[glucose]

100 µM

150 µM

200 µM

50 µM

0 µM

-6.0

-5.0

-4.0

-3.0

-2.0

-1.0

0 30 60 90 120 150

Cur

rent

(µA

)

Time (s)

-6

-4

-2

0 10 20 30 Cur

rent

(µA

)

[lactate] (mM)

[lactate]

5 mM

10 mM

15 mM

20 mM

25 mM

1.90

1.92

1.94

1.96

1.98

2.00

2.02

0 60 120 180 240 300

Res

ista

nce

(kΩ

)

Time (s)

1.90

1.95

2.00

2.05

20 30 40 50 Res

ista

nce

(kΩ

)

Temperature (°C )

temperature 20 °C

25 °C

30 °C

35 °C

40 °C

50

150

250

350

450

550

650

0 240 480 720 960 1,200

Out

put o

f sen

sors

(mV

)

Time (s)

temperature 22 °C

lactate

5 mM

7.5 mM

10 mM

Na+ 20 mM 40 mM 80 mM

K+ 4 mM 8 mM 16 mM

glucose

40 µM 60 µM

80 µM

1.5

1.9

2.3

2.7

20 24 28 32 36 40

Cur

rent

(µA

)

Temperature (°C)

200

300

400

500

Cur

rent

(nA

) 100 µM glucose

5 mM lactate

50

100

150

200

[glu

cose

] (µM

)

0

2.5

5

7.5

10

0 300 600 900 1,200

[lact

ate]

(mM

)

Time (s)

50

75

100

125

150

175

200

0 200 400 600 800 1000 1200 1400

Glucose(Co

ncen

tra.

on(((

no compensation with T compensation

0"

1"

2"

3"

4"

5"

6"

7"

0" 0.5" 1" 1.5" 2" 2.5" 3" 3.5"

Series1"

22 °C 27 °C 32 °C 37 °C

22 °C 27 °C 32 °C 37 °C

50

75

100

125

150

175

200

0 200 400 600 800 1000 1200 1400

Glucose(Co

ncen

tra.

on(((

no compensation with T compensation

0"

1"

2"

3"

4"

5"

6"

7"

0" 0.5" 1" 1.5" 2" 2.5" 3" 3.5"

Series1"

0.24

0.26

0.28

0.30

0.32

0.34

0 15 30 45 60 75

Pot

entia

l (V

)

Time (s)

160 mM

80 mM

40 mM

20 mM

10 mM

[Na+]

210

260

310

360

1 1.5 2 2.5 Pot

entia

l (m

V)

log10([Na+], (mM))

0.21

0.26

0.31

0.36

1 1.5 2 2.5

Pot

entia

l (V

)

log10([Na+], (mM))

0.16

0.18

0.20

0.22

0.24

0.26

0.28

0 15 30 45 60 75 90

Pot

entia

l (V

)

Time (s)

32 mM

16 mM

8 mM

4 mM

2 mM

1 mM

150

200

250

300

0 0.5 1 1.5 2

Pot

entia

l (m

V)

log10([K+], (mM))

[K+]

0.15

0.2

0.25

0.3

0 0.5 1 1.5 2

Pot

entia

l (V

)

log10([K+], (mM))

Interference study

a c d b

e g h f

-600

-500

-400

-300

-200

-100

0

100

0 60 120 180 240 300

Cur

rent

(nA

)

Time (s)

-600 -400 -200

0

0 100 200 300 Cur

rent

(nA

)

[glucose] (µM)

[glucose]

100 µM

150 µM

200 µM

50 µM

0 µM

-6.0

-5.0

-4.0

-3.0

-2.0

-1.0

0 30 60 90 120 150

Cur

rent

(µA

)

Time (s)

-6

-4

-2

0 10 20 30 Cur

rent

(µA

)

[lactate] (mM)

[lactate]

5 mM

10 mM

15 mM

20 mM

25 mM

1.90

1.92

1.94

1.96

1.98

2.00

2.02

0 60 120 180 240 300

Res

ista

nce

(kΩ

)

Time (s)

1.90

1.95

2.00

2.05

20 30 40 50 Res

ista

nce

(kΩ

)

Temperature (°C )

temperature 20 °C

25 °C

30 °C

35 °C

40 °C

50

150

250

350

450

550

650

0 240 480 720 960 1,200

Out

put o

f sen

sors

(mV

)

Time (s)

temperature 22 °C

lactate

5 mM

7.5 mM

10 mM

Na+ 20 mM 40 mM 80 mM

K+ 4 mM 8 mM 16 mM

glucose

40 µM 60 µM

80 µM

1.5

1.9

2.3

2.7

20 24 28 32 36 40 C

urre

nt (µ

A)

Temperature (°C)

200

300

400

500

Cur

rent

(nA

) 100 µM glucose

5 mM lactate

50

100

150

200

[glu

cose

] (µM

)

0

2.5

5

7.5

10

0 300 600 900 1,200

[lact

ate]

(mM

)

Time (s)

50

75

100

125

150

175

200

0 200 400 600 800 1000 1200 1400

Glucose(Co

ncen

tra.

on(((

no compensation with T compensation

0"

1"

2"

3"

4"

5"

6"

7"

0" 0.5" 1" 1.5" 2" 2.5" 3" 3.5"

Series1"

22 °C 27 °C 32 °C 37 °C

22 °C 27 °C 32 °C 37 °C

50

75

100

125

150

175

200

0 200 400 600 800 1000 1200 1400

Glucose(Co

ncen

tra.

on(((

no compensation with T compensation

0"

1"

2"

3"

4"

5"

6"

7"

0" 0.5" 1" 1.5" 2" 2.5" 3" 3.5"

Series1"

0.24

0.26

0.28

0.30

0.32

0.34

0 15 30 45 60 75

Pot

entia

l (V

)

Time (s)

160 mM

80 mM

40 mM

20 mM

10 mM

[Na+]

210

260

310

360

1 1.5 2 2.5 Pot

entia

l (m

V)

log10([Na+], (mM))

0.21

0.26

0.31

0.36

1 1.5 2 2.5

Pot

entia

l (V

)

log10([Na+], (mM))

0.16

0.18

0.20

0.22

0.24

0.26

0.28

0 15 30 45 60 75 90

Pot

entia

l (V

)

Time (s)

32 mM

16 mM

8 mM

4 mM

2 mM

1 mM

150

200

250

300

0 0.5 1 1.5 2

Pot

entia

l (m

V)

log10([K+], (mM))

[K+]

0.15

0.2

0.25

0.3

0 0.5 1 1.5 2

Pot

entia

l (V

)

log10([K+], (mM))

Interference Study

The chemical sensors have good selectivity. Real time temperature compensation is necessary.

Page 14: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Repeatability, Stability and Calibration of the Sensors

For Na and K sensors, one-point calibration is needed.

Na+ and K+ sensors: 1% relative standard deviation in sensitivity Glucose and lactate sensors: 5% relative standard deviation in sensitivity

Na+ Sensors K+ Sensors20

30

40

50

60

70

80

-1 0 1 2 3 4 5

Sen

sitiv

ity (m

v/de

c)

Weeks

20

30

40

50

60

70

80

-1 0 1 2 3 4 5

Sen

sitiv

ity (m

V/d

ec)

Weeks

-400

-350

-300

-250

-200

-150

-100

-1 0 1 2 3 4 5C

urre

nt (n

A)

Weeks

-3

-2.6

-2.2

-1.8

-1.4

-1

-1 0 1 2 3 4 5

Cur

rent

(μA

)

Weeks

Na+ Sensors K+ Sensors

Glucose Sensors Lactate Sensors Glucose Sensors Lactate Sensors-4

-3.5

-3

-2.5

-2

-1.5

-1

0 5 10 15 20

Cur

rent

(μA

)

[Lactate] (mM)

-400

-300

-200

-100

0

0 50 100 150 200

Cur

rent

(nA

)

[Glucose] (μM)

150

200

250

300

350

400

0 1 2 3 4

Pot

entia

l (m

V)

Log10([Na+], (mM))

100

150

200

250

300

350

-1 0 1 2 3

Pot

entia

l (m

V)

Log10([K+], (mM))

Sensor-sensor variations Long term stability

Page 15: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Real time on body sweat analysis

Gao et al. Nature, 2016, 529, 509.

a b c d

‘Smart Wristband’ and ‘Smart Headband’ On Body Validation using Collected Sweat

The Custom-Developed Mobile App

0306090

120

900 1,200 1,500 1,800 2,100 2,400

[Glu

cose

] (μ

M)

Time (s)

20

50

80

110

900 1,200 1,500 1,800 2,100 2,400

[Na+

] (m

M)

Time (s)

ex-situon-body

ex-situon-body

Page 16: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Real time multiplexed sweat analysis during indoor cycling

Gao et al. Nature, 2016, 529, 509.

33 34 35 36 37

T (°

C)

2

5

8

11

[L a

ctat

e]

(mM

)

0 30 60 90

[Glu

cose

] (µ

M)

20

50

80

110

[Na+

] (m

M)

2 5 8

11 14

0 600 1,200 1,800 2,400 3,000

[K+ ]

(mM

)

Time (s)

0

100

200

300

Power(W)

The device can be used to measure detailed sweat profiles and to collect big data.

Sweat starts

Page 17: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Example Application: Dehydration Monitoring toward Sport Medicine

Gao et al. Nature, 2016, 529, 509.

20

30

40

50

60

70

80

0 1,000 2,000 3,000 4,000 5,000 6,000 7,000

[Na+ ]

(mM

)

Time (s)

20

30

40

50

60

70

80

0 1,000 2,000 3,000 4,000 5,000 6,000 7,000

[Na+ ]

(mM

)

Time (s)

dehydration

dehydration

10

20

30

40

50

60

70

80

0 1000 2000 3000 4000 5000 6000 7000

Na+

(mM

)

Time (s)

Subject 1; Water

Subject 2; Water

subject 1; water intakesubject 2; water intake

10

20

30

40

50

60

70

80

0 1000 2000 3000 4000 5000 6000 7000

Na+

(mM

)

Time (s)

Subject 1; Water

Subject 2; Water

subject 3; no water intakesubject 4; no water intake

Sweat sodium can potentially serve as a biomarker for dehydration monitoring.

Page 18: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Wearable Sensors for Ca2+ and pH Monitoring

Nyein, Gao et al. ACS Nano, 2016, 10, 7216.

Kidney function monitoring

Simultaneous monitoring of Ca and pH is essential for accurate Ca analysis.

30

32

34

T (�

C)

Serie…

5.5

6.5

7.5

pH

On-BodypHsensorCommercialpHmeter

00.751.5

2.25

0 5 10 15 20 25 30

[Ca2

+ ] (m

M)

Time (min)

On-bodyCa2+sensorICP-MS

050

100150200

Pow

er O

utpu

t (W

)

pH sensorCommercial pH meter

Ca2+ sensorICP-MS

Temperature

pH selectiveelectrode

Ca2+ selectiveelectrode Temperature

sensor

To FPCB

PVB Reference

Flexible PET

PVB+NaClAg/AgCl Polyaniline

Au

Ca2+H+

Ca2+ sensor pH sensorReference

AuPEDOT:PSS

AuPET PET PET

ETH1001

Ca2+ level in body fluids is dependent on pH

Page 19: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Wearable Sensors for Heavy Metal Monitoring

Gao et al. ACS Sensors, 2016, 1, 866.

Anodic stripping voltammetry for trace level heavy metal analysis

Heavy metal levels in body fluids are extremely low.

Page 20: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Characterization of the Microsensor ArraysAu for Pb, Cu, Hg detection Bi for Zn, Cd, Pb detection

Gao et al. ACS Sensors, 2016, 1, 866.

The microsensor array (Au and Bi) can selectively detect 5 heavy metals.

Page 21: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Heavy Metal Monitoring of Body Fluids

SampleMeasurements from the microsensors (μg/L)

Measurements from ICP-MS (μg/L)

Sweat Cu 249 267Sweat Zn 274 290Urine Cu 571 601Urine Zn 624 634

Zinc detection in human sweat Zinc detection in human urine

Gao et al. ACS Sensors, 2016, 1, 866.

The wearable sensors can accurately measure heavy metals in body fluids.

Page 22: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

How to Access Sweat Sample Without Exercise?

Beyond physical exercise: iontophoresis based sweat extraction

Sweat can be induced on demand through iontophoresis.

Page 23: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

A Wearable Platform for Sweat Extraction & Sensing

a b

Current

Mode 1: Iontophoresis Mode 2: Sensing

Agonist agent sweat

Sensors CathodeAnodeHydrogelHydrogel

Sensor 1 Sensor 2I1 or V1 I2 or V2

Bluetooth transceiver

Phone user interface

Microcontroller

DAC ADC

Low-pass filter

Analog frontend

Sensor A

Low-pass filter

Analog frontend

Sensor B

Current source

Protection circuit

Electrodes/Hydrogel

Mode 1: Iontophoresis Mode 2: Sensing

c

d

Skin Skin

Na ISE

Iontophoresis electrodes

Cl ISE

PVB Reference1 cm

Beyond physical exercise: accessing sweat samples on demand using iontophoresis

Current

Mode 1: Iontophoresis

Mode 2: Sensing

Agonist agent

sweat

Sensors CathodeAnodeHydrogelHydrogel

Sensor 1 Sensor 2I1 or V1 I2 or V2

PNAS, 2017, 114, 4625

Page 24: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Iontophoresis based Sweat Extraction

97

35

284

7.25

1

52 45

354

5.25

9.5

389

60

230.

8

24 35

162

60

252.

4

20

35

111

60

198

23 20

240

60

210

39 30

97

35

284

7.25

1

52 45

354

5.25 9.5

389

60

230.

8

24

35

162

60

252.

4

20

35

111

60

198

23 20

240

60

210

39

30

R ESPON SE LATEN C Y

( SEC ON D S)

R ESPON SE D U R AT ION ( M IN U TES)

PEAK SW EAT R ATE

( N L/M IN /C M 2)

T IM E TO PEAK ( M IN U TES)

T IM E AT PEAK R ATE ( M IN U TES)

Acetylcholine 1% Acetylcholine 10% Methacholine 1%Methacholine 10% Pilocarpine 0.5% Pilocarpine 5%

97

35

284

7.25

1

52 45

354

5.25 9.5

389

60

230.

8

24

35

162

60

252.

4

20

35

111

60

198

23 20

240

60

210

39

30

R ESPON SE LATEN C Y

( SEC ON D S)

R ESPON SE D U R AT ION ( M IN U TES)

PEAK SW EAT R ATE

( N L/M IN /C M 2)

T IM E TO PEAK ( M IN U TES)

T IM E AT PEAK R ATE ( M IN U TES)

Acetylcholine 1% Acetylcholine 10% Methacholine 1%Methacholine 10% Pilocarpine 0.5% Pilocarpine 5%

97

35

284

7.25

1

52 45

354

5.25 9.5

389

60

230.

8

24

35

162

60

252.

4

20

35

111

60

198

23 20

240

60

210

39

30

R ESPON SE LATEN C Y

( SEC ON D S)

R ESPON SE D U R AT ION ( M IN U TES)

PEAK SW EAT R ATE

( N L/M IN /C M 2)

T IM E TO PEAK ( M IN U TES)

T IM E AT PEAK R ATE ( M IN U TES)

Acetylcholine 1% Acetylcholine 10% Methacholine 1%Methacholine 10% Pilocarpine 0.5% Pilocarpine 5%

97

35

284

7.25

1

52 45

354

5.25 9.5

389

60

230.

8

24

35

162

60

252.

4

20

35

111

60

198

23 20

240

60

210

39

30

R ESPON SE LATEN C Y

( SEC ON D S)

R ESPON SE D U R AT ION ( M IN U TES)

PEAK SW EAT R AT E

( N L/M IN /C M 2)

T IM E TO PEAK ( M IN U T ES)

T IM E AT PEAK R ATE ( M IN U TES)

Acetylcholine 1% Acetylcholine 10% Methacholine 1%Methacholine 10% Pilocarpine 0.5% Pilocarpine 5%

97

35

284

7.25

1

52 45

354

5.25 9.5

389

60

230.

8

24

35

162

60

252.

4

20

35

111

60

198

23 20

240

60

210

39

30

R ESPON SE LATEN C Y

( SEC ON D S)

R ESPON SE D U R AT ION ( M IN U TES)

PEAK SW EAT R ATE

( N L/M IN /C M 2)

T IM E TO PEAK ( M IN U TES)

T IM E AT PEAK R ATE ( M IN U TES)

Acetylcholine 1% Acetylcholine 10% Methacholine 1%Methacholine 10% Pilocarpine 0.5% Pilocarpine 5%

97

35

284

7.25

1

52 45

354

5.25 9.5

389

60

230.

8

24

35

162

60

252.

4

20

35

111

60

198

23 20

240

60

210

39

30

R ESPON SE LATEN C Y

( SEC ON D S)

R ESPON SE D U R AT ION ( M IN U TES)

PEAK SW EAT R ATE

( N L/M IN /C M 2)

T IM E TO PEAK ( M IN U TES)

T IM E AT PEAK R ATE ( M IN U TES)

Acetylcholine 1% Acetylcholine 10% Methacholine 1%Methacholine 10% Pilocarpine 0.5% Pilocarpine 5%

Pilocarpine 0.5%Pilocarpine 5%

Methacholine 1%Methacholine 10%Acetylcholine 10%

Acetylcholine 1%

ResponseLatency (s)

ResponseDuration (min)

Time toPeak (min)

Peak SweatRate

(nL/min/cm2)

Time atPeak rate

(min)

Sweat extraction can be controlled by type of drugs and the drug dosage. PNAS, 2017, 114, 4625

Page 25: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Periodical Sweat Extraction using the Wearable Platform

Sweat can be induced periodically.

10 s

300 s

PNAS, 2017, 114, 4625

Page 26: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Example Applications of Wearable Sweat Biosensors

Non-Invasive Glucose MonitoringMedical monitoring and diagnosis without accessing blood

0

30

60

90

120

150

Con

cent

ratio

n(m

M)

Cl- Na+ Na+Cl-

Healthy subjects

Cystic FibrosisPatients

Swea

tglu

cose

(nA)

0

40

80

120

160

Bloo

dgl

ucos

e(m

g/dL

) Fasting After glucose intake

Blood glucose Sweat glucose20

30

40

50

60

70

80

0 1500 3000 4500 6000 7500

[Na+

] (m

M)

Time (s)

dehydration

dehydration10

20

30

40

50

60

70

80

0 1000 2000 3000 4000 5000 6000 7000

Na+ (

mM

)

Time (s)

Subject 1; Water

Subject 2; Water

subject 1subject 2

Wearable sweat sensors enable the correlation studies between sweat biomarkers and blood biomarkers

PNAS, 2017, 114, 4625

Page 27: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Example applications of wearable sweat biosensors

Cystic Fibrosis Diagnosis

Medical monitoring and diagnosis without accessing blood

PNAS, 2017, 114, 4625

Page 28: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Example applications of wearable sweat biosensors

Cystic Fibrosis Diagnosis

Medical monitoring and diagnosis without accessing blood

Wearable sweat sensors can be used for Cystic Fibrosis screening and diagnosis.

0

30

60

90

120

150

Con

cent

ratio

n(m

M)

Cl- Na+ Na+Cl-

Healthy subjects

Cystic FibrosisPatients

Swea

tglu

cose

(nA)

0

40

80

120

160

Bloo

dgl

ucos

e(m

g/dL

) Fasting After glucose intake

Blood glucose Sweat glucose20

30

40

50

60

70

80

0 1500 3000 4500 6000 7500

[Na+

] (m

M)

Time (s)

dehydration

dehydration10

20

30

40

50

60

70

80

0 1000 2000 3000 4000 5000 6000 7000

Na+ (

mM

)

Time (s)

Subject 1; Water

Subject 2; Water

subject 1subject 2

PNAS, 2017, 114, 4625

Page 29: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Drug Monitoring with Wearable Sweat Sensors

Adv. Mater. 2018, 1707442

Page 30: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Methylxanthine Drug Monitoring with Wearable Sweat Sensors

Adv. Mater. 2018, 1707442

Characterization of caffeine sensor

Sweat caffeine vs caffeine dosage (through iontophoresis sweat)

Page 31: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Methylxanthine Drug Monitoring with Wearable Sweat Sensors

Adv. Mater. 2018, 1707442

Dynamic drug metabolism monitoring

Promising use in clinical pharmacology and precision medicine, such as therapeutic drug monitoring, drug abuse intervention, and other aspects of the drug-related healthcare system.

Page 32: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Microfluidic based Sweat Sampling and Sweat Rate Monitoring

ACS Sensors 2018

Sweat composition concentrations and sweat rate are inextricably linked.

Page 33: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Roll-to-Roll Gravure Printing – Mass Production of Sensors at Ultralow Cost

ACS Nano 2018, 10.1021/acsnano.8b02505

This development of robust and versatile R2R gravure printed electrodes represents a key translational step in enabling large-scale, low-cost fabrication of disposable wearable sensors for personalized medicine.

Page 34: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Other promising applications

Exp. Physiol. 84, 401–404 (1999).

Biol Psychiatry. 2008, 64, 907-911

Metabolomics (2016) 12:166

Lung cancer screening

Major depressive disordersSubstance abuse

Page 35: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Nature Electronics, 2018

Bio-Integrated Lab on the Skin

Page 36: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

Wearable/point-of-care devices

• Body fluid analysis – sweat, ISF, plasma, saliva

• Label free protein/hormone analysis

• EEG• ECG• Blood pulse pressure (HR, HRV)• Skin temperature

Machine Learning

Vital sign sensors

Molecular sensors

Page 37: Wearable Biosensors for Personalized Health …...Wearable Sweat Biosensors: System Level Integration The platform consists of disposable sensor patch and reusable flexible printed

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