Ingestible Micro-Bio-Electronic Sensors

for Diagnosis and Monitoring

Dr. Rabia Tugce Yazicigil

Wireless Integrated Systems and Extreme Circuits

Laboratory

Ingestible Micro-Bio-Electronic Devices

Collaborators

Mark Mimee & Phillip Nadeau

Timothy Lu Anantha P. Chandrakasan Giovanni Traverso

Eugenia Inda

2

Tim Lu Group

Traverso Group

Anantha Group

WISE-Circuits Group

3

Wireless Connected Health Monitoring

Fitbit

Microsoft Band

Apple Watch

Fitness trackers and

vital signs monitors

ClearBridge VitalSigns

Vi+al

Sotera Wireless

Wahoo fitness

Biovation

4 BioRad ELISA Kit

Calpro

PSA (Concile™) Tropinin (Ramp™)

Pregnancy test

• Sample acquisition

• Zero electronics

Biochemical Testing

5 Inda et al. JACI 2019

6

Sensor pill

?

GI tract

Proposed System

Nadeau, MIT PhD Thesis 2016

7

Genetically engineer gut bacteria to

detect biomarkers of inflammation

Inda et al. JACI 2019

Biological Sensors

8

Engineered

bacterial cells

Targets

Sugars

Antibiotics

Biochemical

markers

Heavy metals

Readout

Colorimetric

Electrochemical

Fluorescence

Luminescence

Blood

Nadeau, MIT PhD Thesis 2016

9

Proposed System

Bacterial

biosensors

Electronic

readout

circuits

Semi-permeable

membrane

Sensor pill

Target

biomarker

Nadeau, MIT PhD Thesis 2016

10

Proposed System

Bacterial

biosensors

Electronic

readout

circuits

Semi-permeable

membrane

Sensor pill

Target

biomarker ?

Nadeau, MIT PhD Thesis 2016

11

Cellular Programming for Heme

[Courtesy Mark Mimee, Sean Carim, and Timothy Lu]

400 500 6000

0.2

0.4

0.6

0.8

1

Wavelength (nm)

Lum

inescen

ce

(a.u

.)

Wavelength = 490nm

Induction time = 60 min

ON / OFF ratio = 100⨉

Photon flux = ?

12

Avalanche-based photon

counting detector Simulator

Detector counts 4.0 × 104 counts/s

Photon radiance density 5.4 × 106 ph/s/mm2/str/mm

Night sky 3.4 × 107 ph/s/mm2/str

Darkest sky 1.4 × 107 ph/s/mm2/str

Absolute threshold of vision 3.4 × 104 ph/s/mm2/str

Absolute Quantification

Wikipedia

13

Power level Source

Commercial Watt Wall-plug

Research Milliwatt Battery

Future Nanowatt Harvesting

Objectives

(1) Nanowatt power budget

(2) Single supply operation

(3) Demonstrate full system

Luminescence Readout

Nadeau, MIT PhD Thesis 2016

14

How much power is available from harvesting in the GI tract?

Can we make bioluminescence detection low power?

Proposed Electronic System

Nadeau, MIT PhD Thesis 2016

15

(1) Bacterial sensors (2) Detection (3) Circuits

Micro-Bio-Electronic System

Nadeau et al. ISSCC 2018

16

LO

WAKE AFE DIG

REFs + LDOs

CONF

PA

500 μm

Readout Test Chip

Nadeau et al. ISSCC 2018

Physical Measurement Setup

17

PDMS passivation Detectors

ABS plastic chambers

(15 μL)

Test chip

10 mm

Test chassis

NPN

photo-

transistors

PCB

Nadeau et al. ISSCC 2018

Detector Miniaturization

18

Detector part (encapsulated)

PES

membrane

Well

part

Aluminum die

for heating

Nadeau, MIT PhD Thesis 2016

Ingestible Capsule (IMBED) Prototype

19 Mimee et al. Science 2018

In Vitro Evaluation of IMBED

20 Mimee et al. Science 2018

IMBEDs can rapidly detect porcine gastric bleeding

21 Mimee et al. Science 2018

IMBEDs can offer:

Minimally invasive

Rapid

Cost effective detection

Bacterial Sensors:

Environmental resilience

Natural sensing properties

High specificity and sensitivity

Microelectronics:

Complex data processing

Wireless transmission

Ultra low power

22

How Do We Make IMBEDs Practical?

Buffer

solution

Blood

solution Mimee et al. Science 2018

23 [Courtesy V. Altounian, Science]

Acknowledgments

24

Chip design:

Texas Instruments

Hong Kong Innovation and Technology Fund (ITS/195/14FP)

Qualcomm Innovation Fellowship

NSERC fellowship

TSMC University Shuttle Program

Bacterial cell design:

National Institutes of Health (P30DK043351, P50GM098792),

Office of Naval Research (N000141310424, N0001411110725),

National Science Foundation (MCB- 1350625, 1522074),

The Center for Microbiome Informatics and Therapeutics.

On-going research work: Helmsley Charitable Trust

References

25

“An ingestible bacterial-electronic system to monitor gastrointestinal

health”, Mark Mimee, Phillip Nadeau, Alison Hayward, Sean Carim,

Sarah Flanagan, Logan Jerger, Joy Collins, Shane Mcdonnell,

Richard Swartwout, Robert J. Citorik, Vladimir Bulovic, Robert Langer,

Giovannia Traverso, Anantha P. Chandrakasan, Timothy K. Lu,

Science, 25 May 2018: 915-918.

“21.1 Nanowatt circuit interface to whole-cell bacterial sensors," P.

Nadeau, M. Mimee, S. Carim, T. K. Lu and A. P. Chandrakasan, 2017

IEEE International Solid-State Circuits Conference (ISSCC), San

Francisco, CA, 2017, pp. 352-353.

Back-up Slides

27

WAKE7%

AFE1%

DIG + REF + LDOs

0%

LO + PA65%

CONF27%

Off-state power: 2.38 nW Average power

0.1 1.0 10.0 100.0

1

10

100

Measurement rate [min]P

ow

er

[nW

]

Off-state

System Phases

Off-state Wake-up timer plus all leakage

Measure AFE running

TX Transmitting a packet

(152 bits, +2.74 dBm, 1 Mbps, OOK)

Rate Power

20 s (max) 83 nW

10 min 5 nW

System Power

Nadeau, MIT PhD Thesis 2016