biomedical sensors foresight workshop

IFM - Applied PhysicsS 581 83 Linköping, Sweden

Biomedical Sensors Foresight Workshop

with the theme“How do we get there?”

Technology premises and boundariesTechnology driven scenario development:

non invasive monitoring, home tests, early diagnosis,“semicontinuous” health checks, internet based evaluationsand more

Some of the issues: Sensors and instrumentation for primary health care and home based medical tests and diagnosis. De-centralized tests but centralized evaluation.

One interesting question: Dedicated solutions for each parameterof interest or the use of a general platform for all parameters


Suggestion:

Computer screen photo-assisted techniques controlled and evaluated via internet is a promising alternative to a generallyavailable instrumental platform for color based medical tests tobe performed at primary health care units, pharmacies, service houses for elderly and in individual homes


Computer screen photo-assisted techniques (CSPT):

Measuring platform: the use of RGB colors

Light absorption and emission in CSPT

Review of biosensing possibilities with CSPT:Light transmission through melanophores

ELISACell viabilityColorimetry

Difference optical fingerprinting (“CSPT difference spectroscopy”)

CSPT and Google Earth

Ingemar Lundström, 3rd Nordic Workshop on Biomedical SensorsStockholm , March 3, 2006


Measuring platform

Computer Screen Photo-assisted Technique - CSPT

Microtiter plate reading


CSPT reading

D. Filippini, T. Andersson, S. Svensson and I. Lundström,Biosensors & Bioelectronics 19 (2003), 35-41.

each frame is a true color file

rgb

rgb

000000255

000255255

000255000

255255000

255128000

255000000

128000000

097033161

Screen colors through magnitude of intensities of three primaries in 256 levels. Electronically determined through the choice of the three levels (color indices, rgb)


CSPT spectral features

Absorptionsspectroscopy

( ) ( ) ( ) ( )( ) ( ) ( )iIiIiI

iIiIiIiBGR

BGR

000 ++++

=τ

D. Filippini, J. Manzano and I. Lundström, Eurosensors´03, Portugal.

τ(i)


Some examples

1. Microtiter plate with rows of dyes at different concentrations:

AnilineFluoresceinAcridine orangeCy 3RhodamineCy 5


CSPT setup


AnilineFluoresceinAcridineCy 3RhodamineCy 5

Computer light window

Web camera image

1 mM 1µM


Reconstructed assay image


2. COLLAGE OF SINGLE COLOR MICROTITER PLATE RESULTS

1 4

21 24

Light transmission through pigment particle containing cells (melanophores)

ANCA-ELISA test for ulcerative colitis diagnosis (ANCA, Anti-neutrophil cytoplasm antibodies; ELISA, enzyme linked immunosorbent assay)

Cell viability test for antibiotic resistence (yellow salt metabolized into blue product by viable cells)

Melanophoresfrom Xenopuslaevis

Melatonin conc.

Reader 650 nm

CSPT: (255, 000,000)

Reader: 410 nm CSPT: (000, 000,255)


Typical evaluation

salbutamol1 2 3

conc

entra

tion

t = 117 min


Kinetic assay protocolmelatonin


CSPT

eva

luat

ion


Dis

tinct

ive

bioc

hem

ical

imag

es (

usin

g pl

ate

read

er)

Ctrl.


Classification

- 73%, 69%

-17%

, 22%


3. Reflectance fingerprints

( )⎟⎟⎠

⎞⎜⎜⎝

⎛−=

)(log)(

iIiIi

ref

ρ


Colorimetric - 10 parameters in urine


-4 -2 0 2 4-5.5

-5

-4.5

-4

1+

2+ 3+

4+

2nd(

3.39

)Hem

oglo

bin

1st PC (92.3%)-3 -2 -1 0 1 2

-1

0

1

2

neg. 1+

2+ 3+ 4+

2nd(

19.5

)Blo

od

1st PC (71.3%)-1.5 -1 -0.5 0 0.5 1

-1

-0.5

0

0.5

neg.

1+

2+ 3+

2nd(

8.29

)Bilir

ubin

1st PC (82.1%)

-2 -1 0 1 2-2.5

-2

-1.5

-1

normal

1+ 2+ 3+

4+

2nd(

6.02

)Uro

bilin

ogen

1st PC (90.5%)-3 -2 -1 0 1 2 3

-2

-1.5

-1

-0.5

neg. 1+

2+

3+

2nd(

4.84

)Ket

ones

1st PC (90.9%)-3 -2 -1 0 1 2 3

-1

0

1

2normal

1+ 2+

3+ 4+

2nd(

13.4

)Glu

cose

1st PC (82.1%)

-2 -1 0 1 2 3-2

-1.5

-1

-0.5

neg.

1+ 2+

3+

2nd(

6.88

)Pro

tein

s

1st PC (89.8%)-0.2 -0.1 0 0.1 0.2 0.3

-0.2

-0.1

0

0.1

0.2

0.3

neg. pos.

2nd(

11.1

)Nitr

ites

1st PC (13.9%)-1.5 -1 -0.5 0 0.5 1 1.5

-1.5

-1

-0.5

0

neg. 1+

2+

3+

2nd(

5.65

)Leu

kocy

tes

1st PC (90%)

-4 -2 0 2 4-4

-3

-2

-1

0

5

6 7

8 9

2nd(

8.37

)pH

1st PC (89.4%)-4 -2 0 2 4

0

1

2

3

4

1.000 1.005

1.010 1.015 1.020 1.025

1.030

2nd(

6.43

)Den

sity

1st PC (88.8%)0 0.5 1

0

0.5

1

5

10

15

Combur Test classification (under development by RGB Technologies)


MOST “FUNDAMENTAL” APPLICATION SO FAR:Classification of molecules in gas phase with color indicators (with potential applications for breath analysis, food freshness, bacterial classification,…)

“Difference optical fingerprinting”

Arrays of thin films of metallophorphyrins in a PVC matrixOptical properties determined by a sequence of (50) RGB-colors and images stored as individual intensities in the different camera channelsExposure to test molecules (NO, triethylamine, ammonia, CO,…)Difference in intensities in the three channels with and withouttest molecule in the ambient registered for each color index (r,g,b)Each sequence generates 50 data points in each channel of the camera (i.e. 150 points)Classification made by pattern recognition


Illuminating colors

∆ a

bsor

ptio

n∆

emis

sion

red green blue

camera channels

measurementmodel-no emissionmodel-emission

ZnTPP - TEA

ZnTPP I ZnTPP II FeTPP I FeTPP II Biladi I Biladi II

ZnTPP

FeTPP

Biladiene

I II

CSP

T re

spon

se

Illuminating colors

a)

b) c)

1 cm


-10 -5 0 5 10 15 20 25

-10

-5

0

5

10

15

20

25

TEA

NH3

CO

NOx

a)

PC1 (44.2162)

PC2 (24.7038)


-0.5 0 0.5 1-1

-0.5

0

0.5

1

TEA

CO

NOx

NH3

PC1 (55.7881)

PC2

(24.

9305

)

-1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1-0.4

-0.2

0

0.2

0.4

0.6

0.8

1

TEA

CO

NOx NH3

PC2 (24.9305)

PC3

(13.

4139

)

ZnTppFeTpp

Biladieneilluminationcamerachannel

b)

c)


Computers as analytical instrumentsPossibilities:

Light source of any color, intensity and shape through choice ofcolor index

Programmed scanning of colors possible without extra devices

Programmed movement of light spots without extra devices

Chopped light source created by programming

Data collection and evaluation integrated with the light source

Experimental control and data evaluation over internet

RGBTechnologies AB Ongoing commercial development: ”Screenlab”

Target applicationEvaluation of colorimetric assays

PrincipleSpectral fingerprinting with discrimination between absorption and emission signatures

SetupStandard computer set plus a web camera (mobile telephones)

RGBTechnologies AB

One reader for all colorometric testsEnabels multipel test matrixNo expensive equipment (PC and a webcamera) Uses today accepted testschemistry

Multiple tests=>One Multiple tests=>One readerreader


A POSSIBILITY AND A PROBLEM AT THE SAME TIME:

DEVELOP SOFTWARE TO ALLOW AN ARBITRARY SCREEN – CAMERA PAIR TO BE USED, CONTROLLED AND EVALUATED VIA INTERNET


CSPT personal to global monitoring of environmental and sanitary parameters

CSPT spectral fingerprinting Google Earth projected detections

Division of Applied Physics, Department of Physics, Chemistry and Biology, Linköping University

Prof. Ingemar LundströmDr. Daniel Filippini


ACKNOWLEDGMENTS

Daniel Filippini for ideas, models and experimentsCorrado Di Natale, Arnaldo D’Amico, Roberto Paolesse, University of Rome “Tor Vergata” for collaboration on porphyrins and CSPT

RGB Technologies for practical developments of CSPT

VINNOVA, SSF, VR for research grants

For more details see poster by Daniel Filippini


A few references

"Measurement strategy and instrumental performance of a computer screen photo-assisted technique for the evaluation of a multi-parameter colorimetric test strip", D. Filippini, I. Lundström, The Analyst 131 (2006), 111-117.

"Adaptive illumination in computer screen assisted spectral fingerprinting", D. Filippini, I. Lundström, Appl. Phys. Lett. 86 (2005), 084101 1-3. Selected for the Virtual Journal of Biological Physics Research 9 (2005).

"Computer screen photo-assisted detection of complementary DNA strands using a luminescent zwitterionicpolythiophene derivative", D. Filippini, P. Åsberg, P. Nilsson, O. Inganäs, I. Lundström, Sensors and Actuators B (2005), in press

"Generation of biochemical images of different substances using a whole cell assay with multiple signaling pathways",A. Suska, D. Filippini, T. Andersson, I. Lundström, Biosensors and Bioelectronics 21 (2005), 727-734.

"ELISA test for anti-neutrophil cytoplasm antibodies detection evaluated by a computer screen photo assisted technique“D. Filippini, K. Tejle, I. Lundström, Biosensors and Bioelectronics 21 (2005), 266-272.

"Microplate based biosensing with a computer screen aided technique", D. Filippini, T. P. M. Andersson,S. P. S. Svensson, I. Lundström, Biosensors and Bioelectronics 19 (2003), 35-41.

"Computer screen as a programmable light source for visible absorption characterization of (bio)chemical assays",D. Filippini, S. P. S. Svensson, I. Lundström, Chem. Commun. 2 (2003), 240-241.

biomedical sensors foresight workshop

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