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Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis, Ph.D. Associate Professor Dept. of Mechanical Engineering and Dept. of Biomedical Engineering, University of Michigan Visiting Professor at ‘ Demokritos

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Page 1: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

Implantable Biosensors for

Chronic Diseases & Conditions

Nikos Chronis, Ph.D.

Associate Professor Dept. of Mechanical Engineering and

Dept. of Biomedical Engineering,

University of Michigan

Visiting Professor at ‘Demokritos’

Page 2: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

Implantable Biosensors & Actuators

Image taken from : http://mems.colorado.edu/c1.res.ppt/ppt/g.tutorial/ppt.htm

In vivo…

Page 3: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

Measure IntraCranial Pressure (ICP)?

1. Needed after a Traumatic Brain Injury (TBI)

In sports In car accidents

1,5 million cases of TBI every year in the US…

50,000 deaths…

Page 5: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

How ICP is measured?

You need a microsensor…

…a readout system

…A drill and a surgeon

Page 6: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

It is working?

It DOES work for TBI

cases, BUT:

1. The sensor has to be

removed after 5-6 days

2. The patient cannot

move

-Not a solution for long

term monitoring

It does NOT work for

Hydrocephalus cases…

Page 7: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

The Sensor

The

excitation/collection

Head

Filling the gap…

Page 8: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

The Near Infrared (NI) Optical

Window in the Human Body

• HHb (deoxy

hemoglobin) = Hb not

bound to O2

• O2Hb (oxy-

hemoglobin) = Hb bound to O2

• H2O (water), unbound

to proteins

• Bulk Lipid, e.g., oils

There is an optical window between 700-900 nm

when light absorption is MINIMUM !!

Page 9: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

The Implementation

Page 10: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

Architecture of the NiFO MicroSensor

The NiFO (Near-Infrared Fluorescent Optomechanical)

sensor is:

Small, powerless and electronic-free!!!

Page 11: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

The Working Principle of the

NiFO Sensor Human

Tissue

Page 12: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

It does work (ex vivo)!

Normal ICP: 5-15 mmHg

High ICP : > 15 mmHg

The Sensor has a dynamic range that is clinically relevant!

Page 13: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

…and it is also very stable

good for long-term monitoring

Minimum drift over

a 3.5 week period The QDs are extremely stable!

Page 14: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

In vivo ICP monitoring in Sheep

The gold-standard sensor

(the Codman sensor)

The NiFO sensor

Page 15: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

First In-vivo Study: Monitor ICP

fluctuations in an anesthetized animal

Gree Line = Breathing Rate (BR)

Red Line = Oxygen Level

Blue Line = ICP level from the NiFO sensor

Page 16: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

DAY 5

Third In-vivo Study:

Long-term monitoring…in progress

Page 17: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

Other Applications?

Image taken from : http://mems.colorado.edu/c1.res.ppt/ppt/g.tutorial/ppt.htm

In vivo…

Page 18: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

IntraOcular Pressure (IOP) Sensor

- High IOP is a risk factor for developing Glaucoma

Eye Anatomy

- Glaucoma is a chronic disease and the leading

cause of blindness

Page 19: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

The NiFO Sensor for IOP monitoring

Page 20: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

Same working principle,

different microfabrication process

Page 21: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

First study: Cadaver eyes

0

10

20

30

40

50

0 20 40 60

mm

Hg

(Op

tic

al)

mmHg (M)

Day 0

0

10

20

30

40

50

60

70

0 20 40 60 80

mm

Hg

(Op

tic

al)

mmHg (M)

Day 14

1. We integrated the sensor into a

Keratoprosthetic device

2. and implant it into cadaver eyes

Page 22: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

NiFO technology for in vivo pressure

monitoring

Image taken from : http://mems.colorado.edu/c1.res.ppt/ppt/g.tutorial/ppt.htm

In vivo…

Page 23: Implantable Biosensors for Chronic Diseases & Conditionsimel.demokritos.gr/minasens/presentations/N.Chronis.pdf · Implantable Biosensors for Chronic Diseases & Conditions Nikos Chronis,

Behind the scene…

Funding Support:

• National Institute of Neurological Disorders & Stroke (NINDS)

• National Eye Institute

• 2009 NIH Director’s New Innovator Award

• Medical Innovation Center at the University of Michigan

Mostafa Rezaie

Ph.D. Student

Lynda Yang, M.D.,Ph.D.

Department of Neurosurgery

Keith Cook, Ph.D.

Department of Surgery

Shahzad Mian, M.D.

Kellog Eye Center