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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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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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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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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