Nano-Tera 2016 - FlusiTex

7/26/2019 Nano-Tera 2016 - FlusiTex

http://slidepdf.com/reader/full/nano-tera-2016-flusitex 1/30

FlusiTexFluorescence sensing integrated into medical textiles



Full or partial removal of wound pad

Visual Observation

Skin Irritation

Increased chances of infection

Only qualitative information

Current Wound onitoring

Collecting biochemical information

!ighly invasive

"#pensive

Current Methods

Benefits in sensing the wound include $educe hospitali%ation time &rovide better treatment &revents amputation

Wound healing involves a comple# series of biochemical events' (hough ourunderstanding of the healing process has improved) we still use low tech dressings'



*+,bn worldwide market aimed solely at wound care

Wound monitoring consists less than +- of this industry

Frost and Sullivan) edtech insights ,../

0 weeks treatment of a chronical wound 12)... C!F

(he 3usiness Case



Wound

Sensing layer

One fluorescence signalper sensing parameter per wound area

4on5invasive(OF camera

p!)metabolites)o#ygen)6

Working &rinciple

We want to build a wound healing system that can monitor the healingprocess and providing quantitative data'



metabolites and enzymes,

H+, O

!roteins and enzymes

material

""

&ad Structure

Several detection spots on the pad 7microfabricated89

: p!: O#ygen: Various metabolites ; en%ymes: etc'



(he functional pad

<lginate pad with sensor units =elatin) chitosan)Sol5gel matrices

(e#tile wound5pad



Sensing chemistry and matri# development

"n%yme engineering and coupling

Fluorescent lifetime camera development

Coating;microfabrication of wound pad

In vivo evaluation of wound pad

(he (eam

#r$ %uciano Boesel

#r$ &reta Faccio

'rof$ Brigitte (on )echenberg

'rof$ Bradley *elson

#r$ tefano Cattaneo



Wound

Sensing layer

One fluorescence signalper sensing parameter

per wound area


!H

p! Sensing


http://slidepdf.com/reader/full/nano-tera-2016-flusitex 9/30>argaville) (' $'? Farrugia) 3' @'? 3roadbent) A' <'? &ace) S'? Bpton) '? Voelcker) 4' !') Biosens. Bioelectron. ,.+1) D+) 1.5D,'

Healing !rocess acute wound

!ontaneous

ree!ithelisation&ranulationnflammation

n-ury

! H

. ( a l u e s o f w o u n d

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0

1

2Time

p! Senors

Chronic !hase3cute

!hase

! H . ( a l u e s o f w o u n d

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0

1

2Time

n-ury

Chronic wound



p! E p! EG'Gp! EG'1

p! E Gp! E0'G

p! E0'1

p! E 0

p! E2'2p! E 2

Fluorescent p!5marker

27085Carbo#ynaphthofluorescein



: Covalent attachment of transducer to the matrix

Chitosan Fluorescein isothiocyanate (FIT-C)

p! sensing systems

FITC-chitosan



Wound

Sensing layer

One fluorescence signalper sensing parameter

per wound area


Metabolites,

"nzymes,$$

3iomarker Sensing



Fluorescence lifetime imaging

+odulated liht source (<5&)

Phase sensitive detector (T#F

Imaer)

Fre8uency domain

Test taret

5mission 1lter(<on-7ass 1lter)

T#F Imaer (camera)

<5&

5 x c i t a t i o n 5 m i s s i o n

Its di=cult to cali4rate the sensin mechanism 4ased on intensity only,

relia4le results can 4e o4tained 4y measurin the /uorescence life time'



Fluorescence lifetime imaging

We have developed a handheld and e#tremelyportable (OF camera'

We shrink the bulky setup into a handheld device



Sample easurements



<(@<3 =BI Software



Controlling sensors positions

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ensors

)eflector

Currently we are also working on how to precisely position the sensors in thegel matri#'We also want to make sure the sensors donJt leach into the wound



AinKie Shi) >aniel <hmed) Liaole ao) S%5Chin Steven @in) <itan @awit and (ony Aun !uang) <coustic twee%ers9 patterning cells and microparticles using standing surface acoustic waves) %ab onChi!) Vol' /) pp' ,/.5,/2) ,../'

<coustic based particle trapping



(esting in <nimal odels

Pig: Aim 1 testin fresh .ounds

: Feasi4ility for .ound sensor7ad

: Feasi4ility of 7arameters

Pig: Aim 2 testin infected .ounds

: Feasi4ility of 7rimary closure: +onitorin over time

Wound model: Aim 1 >tandardi?ed .ound on

dorsum of 7i@ si?e % x %cm@com7arison .ound 7ad tostandard .ound 4andae,histoloy of .ound healin

Wound model: Aim 2 >tandardi?ed .ound on

ti4ia directly a4ove 4one@ si?e % x%cm@ infection .ith >' aureus@com7arison .ound 7ad tostandard .ound 4andae

<actate7HHistamine"lucoseCyto;ines (I<, TAF)9ric acid

#%

htt7sBB...'e8alix'comBtechnoloy-and-7



<chievements and Future "fforts

: >evelopment of9o p! sensor o biomarker sensorso o#ygen sensor

: Coupling or integration of the sensor systems to;into the coating matri#

: >evelopment of optical setup for fluorescence lifetime imaging in the nanosecondrange

Achievements

Future Efforts

: icrofabrication of the functional matri# on a wound pad

: In vitro and in vivo analysis of the monitor pads

: @ifetime imaging of p! values) biomarker concentrations and o#ygen content with the lifetime camera



&rof' 3rigitte von $echenberg>r' Salim >arwiche

>r' =reta Faccio>r' arkus $ottmar >r' >agmara Aankowska

>r' Stefano CattaneoChristoph !ofer

>r' @uciano 3oesel>r' Claudio (oncelli

>r' <lina Osypova>r' =uido &an%arasa

&rof' 3radley 4elson>r' >aniel <hmed>r' Chen Liang%hong

Than7s8



&evelo7ment of a ratiometric textile sensor for 7H

: 2ased on Flusitex, 4ut concentratin on one 7arameter andusin a sim7ler setu7 closer to industrialisation

: Industrial 7artners

Flusite# =ateway



"antt Chart



"valuation meeting9 4ovember 2) ,.+1

>eliverables

>eliverables for W&+

!onth "eli#erables

$ >esign of the chemical sensing systems

% Surface5functionali%ed nanoparticles

12 Chemical sensors coupled to nanoparticles and silicate matrices

2& Study chemical sensing using nano5sensors and matrices

$% >esign of coating containing nano5sensors and;or silicate matrices

ilestones for W&+

!onth !ilestones

$ &rotocol established for successfully for nanoparticle surface functionali%ation

' &rotocol finali%ed for silicate matri# synthesis

1( Flourescence properties of optical matrices quantified

$) Flourescence properties of optical matrices studied in vitro

>eliverables for W&,

!onth "eli#erables

$ Sensing proteins selected) , en%ymes cloned

% "n%ymes purified and activity tested in vitro

12 , en%ymes coupled to polymeric surfaces 7spheres) gels8) activity tested

2& Study chemo5en%ymatic sensing using nano5sensors and matrices$% >esign and functional coatings containing nano5sensors and;or silicate matrices tested

7e#pansion of the studies to binding proteins) e'g' antibodies8

ilestones for W&,

!onth !ilestones

' Cloned en%ymes biochemically characteri%ed

1( aintaining en%yme activity intact after immobili%ation on polymer surfaces

2% Successful integration of en%yme5polymer matrices onto wound pad

$) In vitro tests of en%yme polymer matrices




>eliverables

>eliverables for W&1

!onth "eli#erables

12 3oard camera prototype with F@I capability

2& Complete) tested F@I camera prototype

$% Improved version of F@I camera prototype

ilestones for W&1

!onth !ilestones

' Solid state modulated light source module

1( Optical setup for fluorescence imaging

>eliverables for W&D

!onth "eli#erables

$ Identification of commercial wound pad

12 4anofabrication of the sensing matrices

1( uantifying and optimi%ing the optical properties of the sensing elements

2& Integrating the sensing elements on the wound pad and measuring their performance

$) Characteri%ing bioadhesion and sensing performance on tissue models

$% easuring the performance of the optimi%ed wound pad design in vivo

ilestones for W&D

!onth "eli#erables

% Surface modification of substrates for nanofabrication

' 4anofabrication of first en%yme5polymer sensing element

2) 3ioadhesive material identified

2% First prototype of wound pad with sensing elements fabricated

$) Final configuration of optical setup and wound pad design




>eliverables

>eliverables for W&2

!onth "eli#erables

12 (wo different wound parameters monitored in vitro with wound liquid from non5infected

and infected wounds

2& (wo different 7p!) and !,O,8 wound parameters monitored in vivo with the demonstrator

of the wound pad

$% $eport on the correlation of the monitored wound parameters to the wound healingprocess

ilestones for W&2

!onth !ilestones

12 Completion of first set of animal e#periments 7>+,8

2& Completion of second set of animal e#periments

$% Completion of pilot human trial



Fa4rication of Aano7article-containin "el Pad

Pt#5PU5CAPs

&is7ersions

>odium

6linate

Aano7article-containin"el Pad

+old Cast Crosslin; .ith CaCl%

>tirrin

Crosslin; .ithCaCl%

6linate "el Pad &is7ersed APs

1 cm



3

Tuneable nanosensors in the dressings

L' >ing et al' Cell se!aration using tilted.angle standing surface acoustic wa(es ) (PNAS)) Vol'+++) pp' +,//,5+,//G) ,.+D'

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ensors



FlusiTex Reader dra.ins



: Covalent attachment of transducer to the matrix

: Physical transducer enca7sulation in hydro7ho4ic matrix

Chitosan Fluorescein isothiocyanate (FIT-C)

Pyranine-CT62 ion 7air com7lex

+T5>

&+&5>

p! sensing systems

Nano-Tera 2016 - FlusiTex

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