The LacriPen™ – A Handheld Portable Ophthalmic

Osmometer and Diagnostic Instrument

…a portable laboratory in the palm of your hand

Presented by:Dr Chris D. Geddes, Ph.D., FRSC Professor, University of Maryland

(UMBC) forLacriScience LLC, Paul T. Gavaris MD

Managing Member

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Osmolarity… Dry Eye… LacriPen™

• Normal homeostasis and clarity of the cornea requires regulated tear flow, the primary driver of which is osmolarity. Therefore, osmolarity is the single biophysical measurement that captures the balance of inputs and outputs within the tear film dynamics. As such it can reliably diagnose dry eye initially and follow the therapeutic response to treatment secondarily. The LacriPen™

© Copyright 2016, LacriScience, LLC Slide LacriScience

Tear Osmolarity and Dry Eye

Tomlinson, et. al.2 - 2006Metadata analysis of peer reviewed measurements for tear samples from normal eyes and subtypes of dry eyes.

Established an osmolarity threshold of 316 mOsm for dry eye diagnosis.

260 280 300 320 340 360 380 4000

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OsmolarityAll Studies 1978-2005

Osmolarity

Pro

babi

lity

Dry EyesMean = 326.9 mOsmS.D. = 22.1 mOsm

Normal EyesMean = 302.2 mOsmS.D. = 9.7 mOsm

315.6 mOsm

2) Tomlinson A, Khanal S, Ramaesh K, Diaper C, and McFadyen A. “Tear Film Osmolarity: Determination of a Referent for Dry Eye Diagnosis”, Investigative Ophthalmology & Visual Science, October 2006, Vol. 47, No. 10

Farris1 - 1994 Suggested that tear osmolarity measurement offers a possible gold standard for the diagnosis of dry eye disease.

1) Farris RL. “Tear osmolarity: a new gold standard?” AEMB. 1994;506: 495–503.

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Point of CareOsmolarity Gold Standard for Dry Eye Stages

Normal 293 to 304 mOsm/L

Mildly dry 305 to 316 mOsm/L

Moderately dry 317 to 328 mOsm/L

Severely dry 329 to 340 mOsm/L

Within a range of only 12 mOsm/L defining the stages, any instrument with a standard deviation above +/- 6 mOsm/L, has no validity for diagnosis and utility in dry eye patient management.

LacriPen™

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© Copyright 2016, LacriScience, LLC Slide LacriScience

Surface Plasmon Resonance:How it Works

Typical SPR ImageThe location of the central minima of the SPR curve is proportional to the refractive index of the tear fluid in

contact with the gold sensing surface.

Light Source

Image Sensor

Tear Fluid

SPRPrism

Gold Film Sensing Surface

SPR “Line”

The Surface Plasmon Resonance Techniquefor Tear Osmolarity Measurement

and more !R

elat

ive

Res

pons

e

SPR Angle (pixels)

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Surface Plasmon Resonance

“Truly rocket science!”

LacriPen™

From bench top…………… to the eye

Rapid Measurements < 1 sec

Disposable – one time use Sensor

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LacriPen™ response to Contrived Tears

280 290 300 310 320 330 340 3508081828384858687888990

855 nm ChannelLinear (855 nm Channel)

Tear Osmolarity, mOsms/L

Pixe

l Num

ber

Linear Response over Dry Eye Range

Instant read-out on Contact with tears

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Rapidly Responds – Large Dynamic SensingRange

250 270 290 310 330 350 37050556065707580859095

100

855 nm Channel

855 nm Channel

Linear (855 nm Channel)

Osmolarity, mOsms/L

Pixe

l Num

ber

• Rapid Measurement < 1 Sec

• Large Pixel Sensing Range 260 – 360 mOsms/L

• Sensitivity +/- 2 mOsms/L

• Highly Sensitive on both Optical Channels

• LacriPen Self-Calibrates

Data recorded on our 3rd Generation prototype

Large Sensing Range

250 270 290 310 330 350 37030

40

50

60

70

80 950 nm Channel

950 nm C...

Osmolarity, mOsms/LPi

xel N

umbe

r

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© Copyright 2016, LacriScience, LLC Slide LacriScience

Patient Response with LacriPen™

Measurement time < 1 sec

Simply touch the tearsthe Pen does the rest !

0 20 40 60 80 100 120 1400500

10001500200025003000350040004500

Pixel Number

Rel.

Inte

nsity

Patient 1

water eye Dry eye

0 20 40 60 80 100 120 140010002000300040005000

Patient 2

Pixel Number

Rel I

nten

sity

water eye Mildly Dry eye

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© Copyright 2016, LacriScience, LLC Slide LacriScience

Point of CareAdjunctive Dry Eye Diagnostics

MMP-91. Identify MMP-9 as low as 5 ng/mL

2. Quantify MMP-9 to monitor treatment

3. No Anesthesia Simply touch tear filmfor instant readout

4. No scraping of eyelid

LacriPen™

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Robust use of Antibodies on Smart Sensors

Antibody, Ab(anti-MMP-9)

Antigen (MMP-9) CM-Dextran Coated Gold slides

Top of sensor prism, gold film

Anti-Fouling coating

Plastic CapGold Film

CM-Dextran CoatingAntibody for analyte, MMP-9, MRSA etc

Surface Blocking, reduce non-specific absorption

Layering of smart sensors

NHS-ester coupling

The Dextran coating is used to routinely anchor surface antibodies or DNA usingwell-known amine Chemistries.

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DiagnosticsA veritable laboratory for real-time patient management

MRSA1. Immediate Diagnosis2. No waiting for cultures3. No need for MRIs4. No need for expensive broad-spectrum antibiotics5. Huge savings in patient care

LacriPen™

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© Copyright 2016, LacriScience, LLC Slide LacriScience

LacriPen™ Diagnostics A veritable laboratory for real time diagnosis and medical management

using – Smart Sensors

Adenovirus No anesthesia, no scrapping of lid especially in children

Bacteria Gram-neg

Biomarkers May detect early cancerEnzymesChemicals

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Q & A

Changing the Way we Thinkabout and Use Ophthalmic Diagnostics

Today

The Lacripen™

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