1. Photonic Remote and Continuous
Biomedical Diagnostics
Zeev Zalevsky 1,2
1
Faculty of Engineering, Bar-Ilan University, Israel
2
SAOT, Friedrich-Alexander Universität Erlangen-Nürnberg,
Germany
1

2. Main collaborators:
Yevgeny Beiderman 1
Javier Garcia 2
Vicente Mico 2
Israel Margelith 1
Asaf Shahmoon 1
Alexander Douplik 3
Dan Cojoc 4
1
Faculty of Engineering, Bar-Ilan University, Israel
2
Departamento de Óptica, Universitat de València,
Spain
3
Ryerson University, Toronto, Canada
4
Trieste, Italy 2

3. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
3

4. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
4

5. Opto-Phone: Hearing with Light
Imaging
module
Camera
Sensor
Invisible L
aser Laser
projection
Any visible distance
5

6. Opto-Phone: Hearing with Light
Hearing with Light: Features
•The ultimate voice recognition system compatible to
“hear” human speech from any point of view (even from
behind).
•There is no restriction on the position of the system in
regards to the position of the sound source.
•Capable of hearing heart beats and knowing physical
conditions without physical contact for measuring.
6

7. Opto-Phone: Hearing with Light
Features- cont.
•Works clearly in noisy surroundings and even through
vacuum.
•Allows separation between plurality of speakers and
sounds sources.
•Works through glass window.
•Simple and robust system (does not include interferometer
in the detection phase).
7

8. Let ’s listen …from 80m
Cell phone Back part of neck
Counting…1,2,3,4,5,6
Counting…5,6,7
X - movement
1
0.5
0
-0.5
(Face (profile
-1
120 140 160 180 200 220 240 260 280 300 320
Heart beat pulse
Counting…5,6
taken from a throat
All recordings were done in a very noisy constriction site at distance of more
than 80m.
8

9. Results: Detection of
occluded objects I
(a). (b). (c).
(a). Camouflaged object. (b). Camouflage without the object. (c). The object (upper left part) and the low
resolution camouflaged scenery.
Spectrogram Spectrogram Spectrogram
0 0 0
2000 900
50 50 50
1800 12
800
100 100 100
1600
700 10
150 150 150
1400
Frequency [Hz]
Frequency [Hz]
Frequency [Hz]
600 200
200 200
1200 8
250 250 500 250
1000
6
300 300 400 300
800
350 350 300 350
600 4
400 400 400 200 400
2
450 200 450 100 450
500 500 500
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
(d). Time [sec]
(e). Time [sec]
(f). Time [sec]
(d). The spectrogram of the camouflaged object with its engine turned on. (e). The spectrogram
of the object with its engine turned on and without the camouflage. (f). The spectrogram of the
camouflaged object without turning on its engine.
9

10. Results: Detection of
occluded objects II
(a). (b).
0 1 2 3 4 5 6 7 [sec]
(a). The scenario of the experiment. (b). Experimental results: upper recording is of the
camouflaged subject. Lower recording is the same subject without the camouflage.
10

11. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
11

12. Technological Description
•Unique technological platform allows remote
and continuous wearable monitoring of many
biomedical parameters simultaneously.
•It is based upon inspection of secondary
speckle pattern back reflected from skin near
main blood artery, after properly adjusting the
imaging optics.
•The biomedical monitoring capabilities include:
heart beats, breathing, blood pulse pressure,
glucose concentration, alcohol level, IOP, blood
coagulation (INR), oximetry, ICP etc.
•Unique patented IP and know how.
•Part of the applications have already been
commercialized. 12

13. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
13

14. Measuring of breathing from rat’s
cornea reflections
Detected rat’s breathing beating at
Noise level
frequency around 1.87Hz.
Reflected speckle pattern.
14

15. Measuring of heart beating from
human’s cornea reflections
(Abs) Spectrum (Abs) Spectrum (Abs) Spectrum
35 25 12
X: 1.502 X: 3.078
X: 1.522 Y: 11.68
30 Y: 33.65
Y: 19.96
10
20
25
8
15
Amplitude
Amplitude
Noise level
Amplitude
20
6
15
Noise level 10
4
10
5
2
5
0 0 0
-20 -15 -10 -5 0 5 10 15 20 -20 -15 -10 -5 0 5 10 15 20 -20 -15 -10 -5 0 5 10 15 20
Frequency [Hz] Frequency [Hz] Frequency [Hz]
Subject #1 (measurement taken while Subject #2 (measurement taken while Reference noise level (detected
subject was holding his breath) subject was holding his breath) reflection from a wall)
Detected heart beating of humans at frequency of around 1.5Hz.
10
20
30
40
Reflected speckles pattern.
50
60
10 20 30 40 50 60
15

16. Measuring breathing of pigs
The swine's
location
25
Breath Breath measured
20 The non-visible
40 m
laser system
15
10
m
B
u
n
p
h
e
a
s
r
t
i
5
Laser beam
0
1 2 3 4 5 6 7 8 9
Experiment
Statistical breathing experiment
16

17. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
17

18. Remote heart beats monitoring
The implemented optical configuration for
remote measuring of heart beats and blood
pulse pressure from subject’s hand
Laser
Camera
50 cm
Hand
3
2
Temporal plot of the outcome from the
2.5
0
system used in the clinical trials for two
2
different participants.
Amplitude [pix]
Amplitude [pix]
1.5 -2
1 -4
0.5
-6
0
-8
-0.5
-10
-1
0 1 2 3 4 0 1 2 3 4
Time [sec] Time [sec]
18

19. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
19

20. Glucose level monitoring
Temporal plot of the outcome from the system used in the clinical tests with the graphical description of the observed
parameters.
20

21. Glucose level monitoring
40 210
35 190
Glucose [mg/dl]
30 170
25 150
20 Glucose /10 130
,
15 Param.6 110
10 90
m
G
m
d
o
u
A
0
1
e
s
c
d
u
p
a
s
e
]
[
/
l
;
]
[
t
i
l
5 70
0 50
0 5 10 15 20 25 30 0 5 10 15 20 25 30
Time [min] time [minutes]
Stability of the system: constant glucose level in blood (denoted Data of subject #1: Glucose level in blood and amplitude
by blue line with triangles) and the estimated parameter 6 of positive peak (parameter #1). Glucose level is denoted
(denoted by magenta line with rectangles). Glucose level is by blue line with triangles and the optically measured
given in units of 0.1[ml/dl] (representing a constant level of 100 parameter is denoted by magenta line with rectangles.
[ml/dl), while the estimated optical values are given in pixels.
21

22. Glucose level monitoring
210 210
190 190
Glucose [mg/dL]
Glucose [mg/dl]
170 170
150 150
130 130
,
110 110
90 90
70 70
50 50
0 10 20 30 40 0 5 10 15 20 25 30
time [minutes] time [minutes]
22
Data of subject #3: Glucose level in blood and amplitude of positive peak Data of subject #1: Glucose level in blood and
(parameter #1). Glucose level is denoted by blue line with triangles and the amplitude of positive peak (parameter #1). Glucose
optically measured parameter is denoted by magenta line with rectangles. level is denoted by blue line with triangles and the
optically measured parameter is denoted by magenta
190 line with rectangles.
170
Glucose [mg/dl]
150
130
110
90 Data of subject #4: Glucose level in blood and amplitude of
70 positive peak (parameter #1). Glucose level is denoted by blue
50 line with triangles and the optically measured parameter is
0 5 10 15 20 25 30 denoted by magenta line with rectangles.
time [minutes]
22

23. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
23

24. Blood pulse pressure
measurement
M , Corr(M , ∆) = 0.99507
140
Systolic
Diastolic
120 ∆ = S-D
Amplitude [mmHg]
100
80
60
40
20
-50 0 50 100 150 200 250 300 350 400
Time [sec]
An example of the obtained remote blood pulse pressure measurement using the proposed device for one subject
participating in the clinical test group. The reference pulse pressure is shown by the green curve (denoted as ∆) was
obtained using manual sleeve based reference measurement device. The blue curve (denoted as M) is the measurement
obtained using the proposed optical technique. The time duration of the measurement was 350sec. The sampling of the
camera was performed at 300Hz. One may see that strong correlation exists between the green (reference) curve and the
blue curve obtained by the developed approach.
24

25. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
25

26. Remote IOP monitoring
The proposed experimental configuration for
remote continuous monitoring of the IOP.
Changing IOP via applying mechanical pressure
on the sclera.
Changing IOP via modifying the height of an
infusion bug.
26

27. Remote IOP monitoring
Data amplitude:
8.02 10.7 11.27 11.6 9.35 7.26 7.22 6.46
With infusion bag
With applied pressure
Experimentally extracted readout compared to
absolute reference IOP measurement obtained
Experimentally extracted readout with Goldmann tonometer.
obtained when changing the height of
the infusion bag every 500 samples.
27

28. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
28

29. Detection of malaria
An example of one out of the 20 relevant inspected parameters. Left: Healthy RBC. Right: Infected RBC.
29

30. Detection of malaria
Separation between infected and
healthy cells. Plotting the length of the
vectors versus cells’ index.
30

31. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
31

32. Remote alcohol level monitoring
(a). (b).
(a). The side (left) and top (right) view of the experimental setup. (b). Typical temporal beating signals extracted
using the proposed remote optical sensing device, before (left) and after (right) the effect of alcohol obtained
over the same subject.
32

33. Remote alcohol level monitoring
Definition of the Ratio wid (through the ratio between the main STD of background noises: long duration test with
and the secondary negative peak’s temporal positions), Main error bars representing the std values of the
sec peak ratio (through the ratio between the main negative measured data.
peak amplitude and the secondary positive peak’s amplitude),
and Standard deviation of background noise (STD) parameters.
33

34. Remote alcohol level monitoring
(a). (b). Summary:
(a). Pulse size, (b). Positive pulse
size, (c). Peakdis, (d). Ratio_wid,
(e). Main_sec_peak ratio, (f). Std
of background noises.
(c). (d).
(e). (f).
34

35. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
35

36. Oximetry and coagulation of blood
Oxygen INR
3.5 3
2.8
3
2.6
2.4
Normilized INR
2.5
Amplitude [pix]
2.2
2 2
1.8
1.5
1.6
1.4
1
1.2
0.5 1
0 2 4 6 8 10 12 0 2 4 6 8 10 12 14 16 18
Test # Exp #
Oximetry experiment Blood coagulation experiment
36

37. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
37

38. Multi-Functional Probe
The edge of the fabricated micro
probe having approximately 5,000
cores while each one of them is
being used as light transmitting
channel (each core is a single
pixel in the formed image). In this
image each core transmits red
channel of light at wavelength of
632nm.
50µm
Laser (632nm) Beam Expander Mirror Laser Controller Camera
Input plane Output plane
Multi core probe F Image
Object
Sample
Location
U1 U2 V
Beam Splitter
Probe Location
1 1 1
+ = Objective Lens
U1 + U 2 V F
38

39. Multi-Functional Probe-
experiments
Experimental results of images transmitted backwards by the proposed micro probe. The scanned objects are as follows;
From left to right: black vertical lines, black rectangles, horizontal black lines, black lines and black rectangle appearing
in the left side of the backwards transmitted image.
5µm
2µm
Experimental results of images with Fe beads having diameter of 1µm imaged
through an agar solution.
39

40. Phantom fabrication
(a) (b) (c)
(a) Fabricated phantom. (b) shows a 3D view sketch of the phantom having two drilled channels with diameter of
400µm each. One longitudinal channel (along the x axis) while another angled channel was made making both
channel crossed inside the phantom. The openings indicated as “in” and “out” enable the connection of microfluidic
system. (c) shows a cross-sectional schematic view of the fabricated phantom.
40

41. Experimental results with
phantom
Experimental results of Fe micro
particles imaged inside a drilled
phantom
Imaging of a manipulated micro wire (indicated by
the solid arrows) inside an hemoglobin mixture.
(a) Top view microscope image of the resolution target. (b) imaging
Imaging of fluorescence protein. HEK 293 cells transfected of the resolution target using the microendoscope device. Inset.
with pEGFP-N3. Left: Top view microscope image. Right: Zoom image of the encompass area. Scales bar of (a) and (b) are 10
Imaging using the microendoscope device. Scales bar of left µm and 20 µm, respectively.
and right image are 50 and 20 µm, respectively.
41

42. Experimental results with
phantom
Monitoring different hemoglobin concentrations inside the phantom.
42

43. In-vivo experimental results
Imaging along a blood vein
of a chicken wing. The solid
arrows indicate the blood
vein, while the dashed arrows
as well as the labeling letter
indicate the cascading point
between the images for
constructing an image with a
larger field of view
43

44. In-vivo experimental results
Imaging of blood vessel inside the rat’s brain using the micro endoscope
44

45. In-vivo experimental results
45

46. Outline
•“Hearing” with light – Introduction
•Biomedical monitoring:
•Introduction
•Measuring of breathing
•Heart beats monitoring
•Glucose level monitoring
•Blood pulse pressure monitoring
•IOP monitoring
•Malaria detection
•Alcohol detection
•Oximetry and coagulation of blood
•Micro endoscope
•Conclusions
46

47. Conclusions:
• A new technology for accurate remote and continuous sensing of
movements was developed.
• The technique is based upon processing of back reflected
secondary speckles statistics.
• We demonstrated remote estimation of breathing, heart beating,
blood pulse pressure, alcohol and glucose concentration in the
blood stream, intra-ocular pressure measurement, oximetry,
coagulation of blood etc.
• To extract precise absolute value for the measured biomedical
parameters periodic personalized calibration is needed every 2-3
years.
• Ultra thin and multi-functional micro endoscope for minimally 47
invasive medical treatment and diagnostics was presented