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PROJECT FINAL REPORT Grant Agreement number: 606100 Project acronym: DIMIDPLUS Project title: Commercialization of an Innovative Microfluidic Impedancebased Device for Multiparametric Cell Analysis Funding Scheme: Demonstration Activity Period covered: from 01/10/2013 to 31/03/2015 Name of the scientific representative of the project's coordinator 1 , Title and Organisation: Adrian Messmer, VP R&D Zurich Instruments AG Tel: +41 44 5150 123 Fax: +41 44 5150 419 Email: [email protected] Project website address: http://www.dimidproject.eu/ 1 Usually the contact person of the coordinator as specified in Art. 8.1. of the Grant Agreement.

PROJECT FINAL REPORT - CORDIS · 2016-08-18 · 4.1 Final&publishable&summaryreport& 4.1.1Executivesummary& 0 Based on the0 scientific0 results0of0 its0 predecessor0 project0 DIMID0GAo286692,

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Page 1: PROJECT FINAL REPORT - CORDIS · 2016-08-18 · 4.1 Final&publishable&summaryreport& 4.1.1Executivesummary& 0 Based on the0 scientific0 results0of0 its0 predecessor0 project0 DIMID0GAo286692,

PROJECT FINAL REPORT Grant  Agreement  number:  606100  

Project  acronym:  DIMIDPLUS  

Project  title:  Commercialization  of  an  Innovative  Microfluidic  Impedance-­‐based  Device  

for  Multi-­‐parametric  Cell  Analysis  

Funding  Scheme:  Demonstration  Activity  

Period  covered:       from     01/10/2013   to     31/03/2015  

Name  of  the  scientific  representative  of  the  project's  co-­‐ordinator1,  Title  and  Organisation:  

 Adrian  Messmer,  VP  R&D  Zurich  Instruments  AG  

 

Tel:  +41  44  5150  123  

Fax:  +41  44  5150  419  

 

E-­‐mail:  [email protected]  

 

Project  website  address:  http://www.dimid-­‐project.eu/

                                                                                                                         1 Usually the contact person of the coordinator as specified in Art. 8.1. of the Grant Agreement.

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4.1 Final  publishable  summary  report  

4.1.1  Executive  summary    Based   on   the   scientific   results   of   its   predecessor   project   DIMID   GAo286692,   the   DIMIDplus   project  GAo606100  has  successfully  commercialized  a  novel,  highly  innovative  technology  for  multi-­‐parametric  single  cell  analysis  based  on  impedance  flow  cytometry.    While  this  new  methodology  was  already  scope  of  researchers  for  several  years,  the  DIMIDplus  project  could  demonstrate   for   the   first   time   the   successful   transfer   of   this   innovation   to   the  markets.   The   competitive  advantages  compared  to  traditional  approaches  like  fluorescence  based  flow  cytometry  could  be  shown  for  several  applications.    

Haematology                                              Milk  Analysis                      Pollen  Analysis    

     

   

Haematology   Milk  Analysis   Pollen  Analysis  

• Reduced  complexity  and  cost  for  diagnostic  applications  

• Reduced   footprint   to   enable  point-­‐of-­‐care  applications  

• Portable   devices   enabling   to  be   used   for   emergency  applications  

• 100%  label  free  

• Reduced  complexity  • No  sample  preparation  • Analysis  of   raw  milk  directly  at  

the  farm    • Footprint  and  portability  

• Today,  the  only  reliable  and  the   most   cost   efficient  methodology   available   to  measure  pollen  viability  

• Footprint  and  portability  

 Besides  the  commercialization  of  three  specific  applications,  the  project  produced  a  new,  highly  innovative  measurement  instrument,  the  MFLI.  This  instrument  is  a  versatile  lock-­‐in  amplifier  and  impedance  analyser,  which   serves   typical   physics   and   biology   applications   like   optical   chopper   and   pulsed   laser   applications,  scanning   microscopy,   material   research   and   impedance   spectroscopy   for   single   cell   analysis.   The  measurement   instrument   is   sold   as   a   bench-­‐top,   stand-­‐alone   product   on   the   one   hand   or   for   integrated  applications  as  an  OEM  version  on  the  other  hand.  

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4.1.2  Summary  Description  of  Project  Context  and  Objectives  

Cell   analysis   has   become   an   important   technique   and  represents  a  fast  growing  market  for  a  wealth  of  applications  in   the   fields   of   life   sciences,  medicine,   environmental,   dairy  and   greenhouse   analytics.   Clinical   (diagnostic)   and   research  applications   in   the   healthcare   and   drug   discovery   markets  demand   rather   complex   analyses   at   the   single   cell   level,  whereas   routine   and   quality   control   applications   in  bioprocess   monitoring   must   presently   content   themselves  with  simpler,  quicker  and  cheaper  analyses.  

What  these  markets  are  calling  for  is  a  device  comparable  to  the   high-­‐end   solutions,   allowing   faster   and   less   expensive  analyses  and  therefore  offering  a  valuable  alternative  for  the  more  price-­‐sensitive  applications,  or  for  real-­‐time  cell  culture  monitoring,   for   which   high-­‐content   analyses   are   presently  not  available.  

In  the  context  of  the  DIMID  project  GAo286692,  the  technology  to  build  such  a  device  has  been  developed  by  a  highly  specialized  Consortium  consisting  of  both  RTD  and  SME  performers.  At  the  end  of  the  project,  a  prototype   has   been   produced   which   has   been   successfully   tested   for   selected   applications   like  haematology  and  dairy  food  quality  analysis.  The  results  obtained  have  carefully  been  analysed  and  were  benchmarked  against  competing  technologies.  Finally,  a  business  plan  was  developed  depicting  a  roadmap  how  to  commercialize  the  DIMID  prototype  and  some  of  its  sub-­‐components.  Under  GAo  606100,  a  follow-­‐up   project   proposal   called  DIMIDplus   has   been   submitted.   This   report   details   the   results   of   the   last   12  months  of  this  demonstration  activity  project.  

The  consortium  of  the  DIMIDplus  project  consists  of  all  formerly  involved  SMEs  (ZURICH,  CELLIX,  CYTOGNOS)  and   is   complemented  by   LABS64   (IT  provider,   specialized   in   software  quality,   verification  and   testing)   and  AMPHASYS  (single-­‐cell  electrical   impedance  technology  leader  and  IPR  holder)  to  commercialize  the  DIMID  device  and  the  electronic  unit  by  verifying  their  performance,  further  testing  to  increase  reliability,  checking  CE  conformity  and  product  packaging.    

An   important   concept   of   the  DIMIDplus   project   is   to  manage   risks   for   the   SMEs   involved.   As   usual  when  working  on  high-­‐potential,  high-­‐tech  products  there  is  a  significant  risk  attached  to  each  application.  For  this  reason   the  DIMIDplus   project   aims   at   exploiting   the  developed   technologies   for  multiple   applications   and  markets.  This  is  happening  at  multiple  levels.  First  ZURICH,  a  supplier  of  technology  for  the  DIMID  device,  will  not   only   deliver   the   electronics   to   the   end   integrator   CELLIX   but   ZURICH  will   also  market   the   technology  directly.   This   significantly   reduces   the   risk   for   ZURICH.   Secondly,   AMPHASYS   and   CELLIX   are   targeting  multiple   applications   like   haematology   assays,   dairy   quality   control   and   pollen   quality   control.   This   again  spreads  the  risk  over  several  fields  of  applications.    

 

 

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Following  on  the  DIMID  project,  the  commercial  objectives  of  the  DIMIDplus  project  are  set  out  as  follows:    

 

                 

 

In  order  to  reach  those  objectives,  a  step-­‐by-­‐step  plan  consisting  of  12  strategic  goals  have  been  defined:  

 

 

Specific  activities  devised   into  five  work  packages  were  carried  out   in  order  to  obtain  the  goals  mentioned  above.  Two  work  packages  (WP  1  &  WP  2)  were  dedicated  to  technical  work,  two  work  packages  (WP  3  &  WP  4)   had   commercial   focus   and  one  work  package   (WP5)  was  dedicated   to  project  management.   In   the  following,  for  each  of  the  work  packages  WP  1  –  WP  4,  the  specific  sub-­‐goals  as  initially  defined  along  with  the  project  plan  are  shown.  

   

1. The update of the suitable business scenarios for the DIMIDplus commercialization and exploitation in line with the interest of the SMEs resulting into various exploitation agreements;

2. Completion of the DIMIDplus portable device for haematology for demonstration purposes towards OEM partners;

3. Completion of the DIMIDsoft impedance flow cytometry software; 4. The execution of the validation plan for the target DIMIDplus haematology, pollen and dairy assays as

defined in period one; 5. Commercialization and market launch of the DIMIDplus portable device for pollen analysis and dairy food

applications under the brand name AMPHA Z30; 6. Commercialization and market launch of the ETZEL lock-in amplifier and impedance analyzer under the

brand name MFLI; 7. The creation of DIMIDplus product folders and training materials and update of the DIMIDplus website; 8. Demonstration of the DIMIDplus products in front of potential customers; 9. Preparation for the scale-up and supply chain of all DIMIDplus products; 10. Creation of a project plan on how to achieve IVDD certification for the DIMIDplus haematology device; 11. The implementation of a Web Shop for the ETZEL for ZURICH;

12. The completion of the plan for using and disseminating knowledge among the SMEs;

The commercial objectives of the DIMIDplus project consist of:

ü Commercialization of multiple high-tech products for multiple fields of applications

ü A DIMIDplus portable device for haematology applications by CELLIX

ü A DIMIDplus portable device for pollen analysis and dairy food applications by AMPHASYS

ü A lock-in amplifier and impedance analyser by ZURICH, here code named “ETZEL”

ü A software for sorting impedance spectroscopic events by CYTOGNOS

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Objectives  and  plan  for  WP1  –  Industrialization  of  “ETZEL”  

• Increasing  stability  and  usability  of  the  software  in  line  with  commercial  requirements  • Set  up  SW  verification  and  regression  environment  • Validating  the  final  hardware  of  ETZEL  • Set  up  calibration  environment  and  implement  calibration  and  burn-­‐in  tests  • Submit  deliverables  D1.1  “ETZEL  Device”  and  D1.2  “ETZEL  Documentation”  

 

 Objectives  and  plan  for  WP2  –  Preparation  for  Market  “DIMID”  

• Execution  of  the  RBC  and  WBC  assay  according  to  deliverable  D2.1  “Validation  Plan”    • Execution  of  the  greenhouse  and  milk  assay  according  to  the  validation  plan  • Finalization  of  the  DIMID  haematology  device  to  achieve  demonstration  level  • Finalization  of  the  DIMID  pollen  analysis  and  dairy  device  in  line  with  commercial  requirements  • Integration  of  additional  SW  requirements  into  DIMIDSoft  for  the  DIMID  greenhouse  and  dairy  device  • Submit  deliverables  D2.2  “DIMID  Device”  and  D2.3  “DIMID  Documentation”  

 

M0 M3 M6 M9 M12 M15 M18

Period  P1 Period  P2

01/10/2013 31/03/201531/03/2014

WP1:  Industrialization  of    -­‐ “ETZEL”      

D1.1

ETZEL  Device  (35.0)

D1.2ETZEL  (2.0)Documentation

(17.0) (20.0)

T1.1.2:  SW  Regression T1.1.3:  SW  Pack

T1.2.1:  HW  Performance  Optimization

T1.3:  Documentation

T1.1.1:  SW  Optimization  &  Verification

T1.2.2:  HW  Casing T1.2.2:  CE  Conformity  Testing

M0 M3 M6 M9 M12 M15 M18

Period  P1 Period  P2

01/10/2013 31/03/201531/03/2014

WP2:  Preparation  for  Market  – “DIMID” (28.0) (8.5) (12.0) (23.0)

D2.1

Validation  Plan  (2.5)

T2.2.2:  Assay  ValidationT2.2.1:  Assay

T2.3.1:  SW  Event  Clustering

T2.5:  Documentation

T2.4.1:  HW  Casing T2.4.2:  CE  Conformity

D2.2

DIMID  Device  (65.0)

D2.3DIMID  (4.0)DocumentationT2.1:  Chip  optimization  &  Fluidics  handling

T2.3.2:  SW  Integration  /  UI   T2.3.3:  SW  Pack

T2.0  (new):  DIMIDSoft  Adaption  for  AMPHASYS  

(Evaluation)

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Objectives  and  plan  for  WP3  –  “DIMID”  Commercialization  and  Marketing  

• Define  and  submit  the  business  plan  D3.1  “Business  Plan”.  • Deliver  D3.2  “Patent  Search”:  Carefully  monitor  the  risk  of  patent  infringements.  • Submit  deliverable  D3.3  “Report  on  Scale-­‐up  and  Supply  Chain  Management”:  The  DIMID  and  ETZEL  

contain  several  critical  components,  which  require  careful  risk  management  of  the  supply  chain.  • Submit  deliverable  D3.4  “Product  Folder”:  all  marketing  material  need  to  be  ready  for  the  respective  

product  launches,  namely  leaflets,  brochures,  specifications,  advertisements  and  product  web  sites.  • Implement,  test  and  document  the  web  shop,  submit  deliverable  D3.5  “Web  Shop”.  

Objectives  and  plan  for  WP4  –  Trainings  and  Customer  Demos  

• Prepare  training  material  and  perform  customer  demonstrations  • Submit  the  deliverables  D4.1  “Training  Material”  and  D4.2  “Report  on  Customer  Demos”  

 

M0 M3 M6 M9 M12 M15 M18

Period  P1 Period  P2

01/10/2013 31/03/201531/03/2014

WP3:  Commercialization  and  Marketing

D3.3Report  on  Scale  up&  SCM  Status  (3.0)

D3.4ProductFolder  (10.5)

(11.0) (13.0) (3.5) (6.0)

D3.1

Business  Plan  (6.0)

D3.2

Patent  Search  (1.0)

D3.5WebShop  (13.0)

T3.3:  Business  Plan

T3.1:  Market  Study

T3.4:  Development  of  Scale  Up  &  SC

T3.2:  Patent  Search

T3.5:  Marketing  Material

T3.6:  Development  of  Web  shop

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4.1.3  Main  Results  

Results  achieved  under  WP1  –  Industrialization  of  “ETZEL”  

Main   focus  of   this  work  package  was  on   the  preparation  of   the  market   launch  of   the  ETZEL  measurement  instrument.  A  major  part  of   the   staff   of   Zurich   Instruments  was  working   in  parallel   on   creating  marketing  material,  commercial  ads,  product  user  and  programmers  manuals  and  product  videos.  In  parallel,  the  ETZEL  hardware   and   software   validation   tasks   were   taking   most   of   the   attention.   On   the   hardware   side,   two  further   design   spins   were   required   mainly   with   the   focus   on   noise   performance   improvements.   On   the  software   side,   there   were   three   areas   of   focus,   which   were   executed   in   close   collaboration   with   the  consortium  partner   LABS64:   functional   verification   including   setup  of   a   complete   regression   environment,  increased  stability  and   improved  usability.  For   the   latter  one,  a  graphical  view  of   the  main   lock-­‐in   tab  was  added   to   the   LabOne   measurement   software   package.   Other   activities   focused   on   the   scale-­‐up   of   the  manufacturing   and   warehousing   processes.   The   anticipated   sales   volume   of   the   MFLI   required   the  introduction  of  a  company  wide  ERP  system  including  the  setup  of  a  web  shop.  Both  systems  were  defined,  implemented  and  verified  during  the  second  period  of  the  project.  On  January  30th,  2015,  Zurich  Instruments  launched  the  ETZEL  under  the  brand  name  MFLI  to  the  market.  All  product  is  found  under:  

http://www.zhinst.com/products/mfli.  

All  deliverables  of  this  work  package  were  submitted  on  time,  namely  the  ETZEL  device  and  documentation.  

D1.1  “ETZEL  Device”:  

       

 

For  more  information  on  the  product,  a  short  video  is  available  under:  

https://www.youtube.com/watch?feature=player_embedded&v=5ihQH0hCmr4    

The  new  product  is  intended  to  become  the  new  standard  for  lock-­‐in  amplifiers  in  the  frequency  range  of  up  to  500  kHz  challenging  the  current  market  leader,  the  SRS  830:  

 

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The  MFLI  product  comes  along  with  an  outstanding  tool  set:  LabOne.  

 

 

D1.2:  “ETZEL  Documentation”  

The  MFLI  comes  with  a  detailed  set  of  user  documentation.  For  detailed  information,  please  refer  to:  

http://www.zhinst.com/products/mfli.  

 

 

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Results  achieved  under  WP2  –  Preparation  for  Market  “DIMID”  

In  work  package  two,  the  consortium  partners  CELLIX,  AMPHASYS  and  CYTOGNOS  worked  in  parallel  on  the  market  preparation  for  their  products.  

D2.1  “Assay  Validation”  

The  main  focus  on  CELLIX  side  was  on  the  RBC  and  WBC  haematology  assay  validation  including  creation  of  a  draft  project  plan  on  how  to  achieve  IVDD  certification:  

 

 

In   parallel,   the   portable   DIMIDplus   haematology   analyser   was   further   integrated   and   brought   to   a   stage  where   it   can   be   deployed   to   potential   OEM   partners.   First   clinical   tests   with   volunteers   were   setup.   On  January  29,  CELLIX  successfully  demonstrated  the  DIMIDplus  haematology  device  at  the  premises  of  Zurich  Instruments   in  the  context  of  a  F2F  consortium  meeting.  Blood  of  several  volunteers  of  Zurich  Instruments  was   measured   demonstrating   the   performance   of   the   device   and   assay   including   the   analysis   of   cell  populations  with  the  DIMIDsoft  provided  by  CYTOGNOS.  

 

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On  the  side  of  AMPHASYS,  the  key  activities  were  related  to  the  validation  of  the  assays  for  pollen  analysis  and  dairy  food  applications.  

The  first  priority  was  on  the  successful   launch  of  the  pollen  analysis  assay.  For  the  determination  of  pollen  viability  no  standard  method  exists.  Individual  seed  companies  have  developed  their  own  protocols  that  rely  basically   on   some   published   data   and   depend,   of   course,   on   the   sort   of   pollen   to   analyse.   Most   seed  companies  have  validated   the  AMPHASYS   technology  with   their  methods,  but  do  not  want   to  disclose   the  data.  

However,   analyses   were   performed   at   0.5   and   12   MHz   and   compared   with   pollen   stained   with   FDA/PI  (Fluorescein  Diacetate   /   Propidium   Iodide),   a   fluorescence   dye  mixture   that   selectively   reveals   viable   and  dead  cells  by   fluorescence  microscopy.  Pictures  of   the  stained  samples  are   taken,   the  green   (DAPI,  viable)  and   red   (PI,   dead)   cell   counted   and   the   obtained   ratios   compared  with   the   analyses   performed  with   the  DIMIDplus  device.  A  very  high  correlation  between  both  methods  could  be  demonstrated.    

 

 

Based  on   the  excellent   results,  AMPHASYS   successfully   launched   the  DIMIDplus  device   for  pollen  analysis,  named  as  AMPHA  Z30  to  the  market  in  April  2014.  

 

 

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During   the   last   6   months   of   the   project,   AMPHASYS   increased   its   focus   on   the   milk   assay.   Several  laboratories  were  contacted  and  the  device  was  demonstrated  to  customers  in  Switzerland  and  France.  The  performance   of   the   assay   continuously   improved   and  was   finally   benchmarked   against   traditional,   optical  based  technologies.  An  evaluation  of  the  technology  was  done  with  a  prototype  of  the  AMPHA  Z30.  Samples  were  measured  at  the  facility  of  Amphasys  and  at  Swissmilk  (Zollikofen,  CH).  The  data  provided  evidence  of  a  good   correlation   between   the   DIMIDplus   for   somatic   cell   count   on   raw  milk   and   the   Fossomatic   device,  which  is  considered  to  be  the  gold  standard.  

 

 

 

y  =  0.8942x  +  36807  R²  =  0.98525  

0  

500000  

1000000  

1500000  

2000000  

0   200000   400000   600000   800000   1000000   1200000   1400000   1600000   1800000  

Amphasys  cells/m

l  

Fossomatic  cells/ml  

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D2.2  “DIMID  Device”  

During  the  DIMIDplus  project,  both  CELLIX  and  AMPHASYS  further  improved  their  DIMID  devices.  Below  the  pictures  are  shown  for  the  portable  DIMID  haematology  analyser  that  is  used  as  a  demonstrator  for  potential  OEM  partners  and  the  DIMID  device  for  pollen  analysis  and  dairy  food  applications.  

 

                                             

 

 

 

 

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D2.3  “DIMID  Documentation”  

This   document   was   written   in   tight   collaboration   with   CELLIX,   AMPHASYS,   ZURICH   and   CYTOGNOS.   It  contains  three  main  sections,  which  are  related  to  the  DIMID  device  for  haematology,  the  DIMID  device  for  pollen  and  milk  analysis  and  the  DIMIDSoft  impedance  flow  cytometry  analysis  software.  

a)  DIMIDplus  Portable  Device  for  Haematology  

The  documentation  part   for   the  DIMIDplus  portable  device   for  haematology  has  been  made  available  and  serves   as   a   base   for   further   steps   towards   final   commercialization   in   collaboration  with   a   potential   OEM  partner.  In  particular,  it  contains  all   information  about  the  sub-­‐systems  of  the  device,  the  validation  results  of  the  RBC  and  WBC  assays  and  a  roadmap  towards  IVDD  certification.  

b)  DIMIDplus  Device  for  Pollen  Analysis  and  Dairy  Food  Applications  

The  documentation  part   for   the  DIMIDplus  device   for  pollen  analysis  and  dairy   food  applications  has  been  made  available  and  serves  as  a  base   for  manufacturing.   In  particular,   it   contains  all   information  about   the  sub-­‐systems  of  the  device  and  the  validation  results  of  the  pollen  and  milk  assays.  

c)  DIMIDSoft  Analysis  Software  for  Impedance  Flow  Cytometry  Data  

The  documentation  part   for   the  DIMIDSoft  analysis  software   for   impedance  flow  cytometry  data  has  been  made   available.   It   describes   an   overview   of   the   software   architecture.   Even   if   DIMIDSoft   scope   was   not  foreseen   to  pass  a  potential   IVD  certification  audit,   the   ISO:  13485  and  UNE:  62304  SOPs   implemented  at  CYTOGNOS   for   software   design   and   development   would   allow   complying   with   IVD   requirements   rather  straightforward.    

 

           

   

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Results  achieved  under  WP3  –  Commercialization  and  Marketing  

The   work   performed   in   work   package   three   included   mainly   the   study   of   the   relevant   markets   and   the  preparation  of  marketing  material  like  product  folders  and  videos  and  the  scale-­‐up  for  production  ramp-­‐up  of  the  various  devices.  

All  deliverables  of  this  work  package  were  submitted  on  time  or  with  a  minor  delay.  

D3.1  “Business  Plan”  

A  detailed  business  plan  was  defined  based  on  several  market  studies  performed.  A  lot  of  emphasis  was  put  on  understanding  the  competitor  landscape  for  the  various  technology  offerings:  

Competitive  comparison  haematology  analyser  market:  

Company   Cellix   Samsung   Abbott   Horiba   Sysmex  Device   DIMIDplus  

 

   

LabGeo  HC10    

 

Cell-­‐Dyn  Emerald  

 

HHi  2K,en  Derzlic    

 

pocH-­‐100i    

 

Dimensions  (HxWxD)  

10.6”  x  11.8”  x5.9”  27  x  30  x  15(cm)  

14.5”  x  13.5”  x  11.5”  39  x  34.4  x  29.3  (cm)  

13.8”  x  9.8”  x  13.8”  13  x  25  x  35(cm)  

16.5”  x  14”  x  12.5”  41.9  x  35.6  x  31.8  (cm)  

7.3”  x  13.8”  x18.1”  18.5  x  35  x  46  

Weight  (lbs/kg)  

5.5lbs  /  2.5kg   28lbs  /  12.8kg   20lbs  /  9kg   31lbs  /  14kg   30.8lbs  /  14kg  

List  Price   €6,000  /  $8,000   €2,800  /  $4,841  *Source:  http://www.medicalequipmentcentre.com/  

€22,000  /  $30,000   €16,500  /  $22,500   €13,200  /  $18,000  

Used   N/A   Unknown   €3,700  –  5,900  /  $5,000  

€4,400  /  $6,000   €1,800  /  $2,500  

Parameters   RBC,  WBC  &  WBC-­‐3  diff.    

18  parameters:  WBC-­‐3  diff,  WBC,  LYM,  MON,  GRA,  LYM%,  MON%,  GRA%,  Hb,  HCT,  RBC,  MCV,  MCH,  RDW,  MCHC,  PLT,  PCT,  MPV,  PDW  

18  parameters:  WBC,  RBC,  Hb,  Hct,  MCV,  MCH,  MCHC,  PLT,  %&#  neut,  mono,  lymph,  eos,  baso    

CBC  Mode  (16  parameters):  WBC,  RBC,  HGB,  HCT,  MCV,  RDW,  MCH,  MCHC,  PLT,  MPV,*PCT,*PDW,  %  and  #  of  LYM,  MON  and  GRA    

Whole  blood  mode:  17  parameters  with  3-­‐part  Differential  Pre-­‐dilute  mode:  8  Parameters,  which  includes  WBC,  RBC,  HGB,  HCT,  MCV,  MCH,  MCHC,  PLT  

CV     3%  WBC  count  3%  RBC  count  

1.6%  WBC  count  1.3%  RBC  count  0.8%Hb  3.3%  platelet  

3.5%  WBC  count  2.0%  RBC  count  2.1%Hb  6.1%  platelet  1.7%  Hct    0.8%  MCV    

2.5%  WBC  count  2.0%  RBC  count  1.5%Hb  5%  platelet  (WB  or  PLT  concentrate)  2%  Hct    

 

Min  Volume    

25  µL   25  µL   9.8  µL   10  µL   15  µL  

Time  to  result    

~60  seconds     45  seconds          

Sample  type    

EDTA  whole  blood     EDTA  whole  blood       WB,  PRP     WB  and  pre-­‐dilute    

Throughput     Unknown     80  samples  /  hr     60  samples  /  hr     60  samples  /  hr     25  samples  /  hr    

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The  demand  for  haematology  analysers  is  influenced  by  the  development  of  alternative  technologies  such  as  point-­‐of-­‐care  (POC)   instruments  and  integrated  analysers,  advancements   in  product  automation  and  highly  streamlined   lab  processes.    Cell  analysers  presently  available   for   lab  purpose  are  multi-­‐channelled,  as  they  analyse  various  haematology  measurements  utilizing  diverse  techniques.    A  number  of  patients  prefer  home  monitoring  devices.        

Developing   products   by   integrating   complementary   technologies   such   as   imaging,   software,   HT   and  multiplexing  in  compact  bench  top  flow  cytometers,  which  may  target  POC  markets  can  help  market  players  gain   a   substantial   boost   in   sales.     Existing   players   have   already   started   considering   the   importance   of  automation   and   sample   handling;   however,   there   is   still   a   lot   of   scope   in   this   space,   as   developing   flow  cytometers   with   integrated   sample   automation   can   save   costs   significantly   by   reducing   the   amount   of  sample  volume  and  offering  HT.    Also,  automation  can  enable  rapid  data  exchange  across  different  systems.    With  increasing  focus  on  the  need  for  HT,  there  would  also  be  a  continuous  need  for  advanced  software  that  can   analyse   and   manage   the   large   amount   of   data   generated.     Thus   the   market   players   can   tap   this  opportunity.     The   DIMIDplus   haematology   device   is   a   small,   portable,   low-­‐cost   system,   which   can   target  applications  in  point-­‐of-­‐care  settings  such  as:  

• Emergency  rooms  where  devices  may  need  to  be  moved  to  the  patient  bed-­‐site  • Mobile  first  responders  including  air  and  ground  ambulances  • Remote  medical  centres  or  satellite  hospitals.  • Doctor’s  office  

The  attractiveness  of  the  compact  footprint  of  the  DIMIDplus  device  was  echoed  during  interviews  with  key  stakeholders.   Further   benefits   of   the   DIMIDplus   haematology   device   include   leveraging   the   microfluidic  nature  of  the  device  thereby  enabling  the  targeting  of  specific  patients  such  as  neonates  and  children  where  typical  blood  volumes  are  in  the  region  of  1-­‐4mL.    

Going   forward,   the   global  market   for   in   vitro   diagnostic   products  will   remain   captive   to   the   growing   and  significant   financial   challenges   facing   health   care   delivery   systems   as   population   age   and   underserved  populations   demand   improved   care.     The   advent   of   Obamacare   in   the   US   is   expected   to   particularly  constrain   service   and   product   pricing   in   that   nation   as   the   delivery   system   attempts   to   accommodate  significantly  more  patients,  many  of  whom  have  the  expensive  “triad”  of  diseases  –  obesity,  diabetes,  and  hypertension.     Other   developed   nations   will   also   be   coping   with   aging,   sicker   populations,   pushing   their  health   delivery   systems   to   the   limits.     For   these   reasons,   health   care   systems   and   players   are   looking   for  disruptive   technologies   that   significantly   reduce   costs,   significantly   improve   health   care   or   preferably   do  both.     This  will   raise   the  bar   for   companies   seeking   to  develop  blockbuster  products,   as   technologies   that  offer  incremental  improvements  will  not  see  broad  application.  

On  the  risk  side  to  enter  these  markets,  the  regulatory  constraints  need  to  be  well  understood.   In  Europe,  the   Directive   98/79/EC   of   the   European   Parliament   and   of   the   Council   of   27   October   1998   on   in   vitro  diagnostic  medical  devices  and  successive  amendments  and  corrections,  aims  at  creating  a  single  market  and  reducing  technical  barriers  to  trade  for  medical  devices.  It   introduces  common  regulatory  requirements  for  IVDs  across  Europe,  bringing  IVDs  in   line  with  other  medical  devices.    The  Directive  lays  down  harmonising  rules  designed  on  the  safety,  quality  and  performance  of  IVDs.  In  the  USA,  the  procedure  on  how  to  market  a  diagnostic  device  is  well  explained  on  the  FDA  website:  

http://www.fda.gov/medicaldevices/deviceregulationandguidance/howtomarketyourdevice/default.htm  

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Comparative  comparison  milk  analysis:    

The  quality  of  milk  is  among  others  assessed  by  counting  the  number  of  bacterial  and  somatic  cells.  Current  analytical   instruments   are   too   complex   and   expensive   (instruments   and   assay   costs)   for   most   dairy   food  producers.   Therefore,   thousands   of   samples   are   screened   daily   by   simple   qualitative   tests,   which  occasionally  fail  causing  costly  production  losses.  

Ampha  Z30   represents  a   low-­‐cost,  easy-­‐to-­‐use  device   that  can  be  used   for  both  bacterial  and  somatic   cell  counting.  So  far,  there  is  no  solution  on  the  market  for  a  simultaneous  count  of  bacterial  and  somatic  cells.  Amphasys’   technology   could   fill   that   gap   and   achieve   a   comfortable   position   if   the   analysis   is   possible  directly  on  raw  milk.  In  the  course  of  the  DIMIDplus  project,  this  was  successfully  demonstrated.  

 

In  contrast   to   the  haematology  market  described  above,  somatic  and  bacterial  cell  counting  of   raw  milk   is  not   subjected   to   severe   regulatory   norms.   The   qualification   of   the   product   quality,   however,   is   clearly  defined   and   regulated,   which  means   that   cell   counters   do   need   to   fulfil   counting   precision   and   accuracy  criteria   for   being   used   in   the   qualification   process.   The   technology   must   therefore   prove   to   meet   the  specifications   of   the   established   and   accepted   analysers   (from   FOSS   or   Bentley   Instruments),   which   will  require  regular  calibrations  and  validations  of  the  systems.  

The  development  of  a  specific  sales  force  for  the  milk  analysis  application  seems  not  to  be  the  optimal  choice  for   penetrating   the  market.   Partnering  with   one   of   the   larger   companies   (FOSS,   for   example)   as   an  OEM  supplier  would  provide  a  much  faster  access  to  this  large  market.  

 

 

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Comparative  comparison  pollen  analysis:  

Presently,  the  only  alternative  to  determine  pollen  viability  is  either  using  fluorescent  dyes  and  counting  the  cells   with   microscopes,   or   performing   germination   assays,   which   however   take   a   lot   of   time.   Amphasys’  impedance  flow  cytometer  will  clearly  fill   this  technological  gap.  The  table  below  lists  current  technologies  used  and  compares  it  with  Amphasys’  solution.  

Technology Impedance Flow Cytometry

Fluorescence microscopy In vitro germination

Device   Ampha  Z30  Fluorescence  Microscope  

Petri  dish  

Throughput   20  analyses  /  h   6  analyses  /  h   100  analyses  /  day  

Reproducibility   High   Low   Low  

Analysed  cells  /  test   10’000-­‐50’000   <  50   <  50  

Reliability   High   Low   Low  

Specificity  towards  pollen  types    

Low   High   High  

Suitability  for  greenhouse   Yes   No   Not  effective  

Portability   Yes   No   Yes  

.

 

 

(A)  Pollination  results  expectedly  in  no  fruits  at  all.  (B)  Correlation  between  measured  pollen  viability  and  production  of  embryos,  which  generate  new  plants.  (C)  Typical  seed  setting  curve  for  tomato  resulting  from  pollen  viability  analysis  with  Amphasys’  device.    

C  

Pollinated  with  31%  viability

Pollinated  with  3%  viability

Pollinated  with  0.1%  viability

A   B  

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D3.2  “Paten  Search”  

The  patent  search  was  executed  by  CELLIX  with  support  of  AMPHASYS.  The  study  was  executed  taking  into  account   the   key   objectives   of   the   DIMIDplus   project   and   subsequently   distributed   to   the   DIMIDplus  consortium   in   order   to   avoid   possible   patent   infringements.     This   study   acted   as   well   as   an   aid   for   the  consortium  to  define  an  appropriate  IPR  protection  strategy.  

D3.3  “Report  on  Scale-­‐Up  and  Supply  Chain  Management”  

The  work  on  a  scale  up  concepts  and  basic  supply  chains  for  all  three  products  resulting  out  of  DIMIDplus  has  been   reported   in   D3.3   “Report   on   Scale   Up   and   SC   Status”.   The   DIMIDplus   Consortium   has   a   highly  interlinked  supply  chain  strategy  with  strong  mutual  dependencies.  

 

All   partners   have   performed   a   detailed   risk   assessment   creating   awareness   of   their   supply   chain  dependencies  and  how  this  might  impact  their  ramp-­‐up  schedule.  Where  possible,  a  second  source  supplier  has  been  defined.  However,  this  was  not  feasible  for  all  critical  parts  of  the  respective  products.    

In  order  to  mitigate  those  risks,  the  partners  are  currently  negotiating  OEM  respectively  license  agreements  for  critical  parts  that  have  no  obvious  alternative  for  second  source  supply.  

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D3.4  “Product  Folder”  

All   partners   developed   marketing   material   for   their   respective   products.   Below   a   small   excerpt   of   the  respective  product  folders:  

Product  Folder  MFLI:  

 

     

 

Product  Folder  DIMID  device  for  haematology:  

 

         

 

 

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Product  Folder  AMPHA  Z30:  

 

         

 

Product  Folder  DIMIDSoft:  

 

         

 

For  further  information,  please  refer  to  the  relevant  product  pages:  

• http://www.zhinst.com/products/mfli  • http://cellixltd.com/products  • http://www.amphasys.com/impedance-­‐flow-­‐cytometry  • http://www.cytognos.com/dimidsoft  

Page 21: PROJECT FINAL REPORT - CORDIS · 2016-08-18 · 4.1 Final&publishable&summaryreport& 4.1.1Executivesummary& 0 Based on the0 scientific0 results0of0 its0 predecessor0 project0 DIMID0GAo286692,

D3.5  “Web  Shop”  

The  MFLI  is  the  third  product  platform  of  ZURICH  and  covers  the  frequency  range  of  50  kHz  to  5  MHz.  It  has  been   launched   to   the  market   January  30th,  2015  under   the  brand  name  MFLI.  The  MFLI  platform  has   the  potential  to  reach  a  sales  volume  of  1000  units  per  year  by  end  of  2018.  

This  strong  growth  requires  dedicated  strategies,  which  target  on:  

•   Efficiency  of  the  pre-­‐sales,  sales  and  post-­‐sales  processes  including  provision  of  a  webshop  

•   Efficiency  and  scale-­‐up  of  the  supply  chain  including  manufacturing  and  warehousing  

As  a  consequence,  ZURICH  decided  to  define  an  IT  Integration  strategy,  which  has  been  implemented  and  is  reflected  in  the  deliverables  D3.3  “Report  on  Scale-­‐Up  and  SCM”  and  D3.5  “Webshop”.  

At  the  end  of  the  DIMIDplus  project,  two  essential  elements  of  this  strategy  are  now  available:  the  Webshop  and  the  ERP  manufacturing  and  warehouse  modules.  

With   those   two   elements   in   place,   ZURICH   is   prepared   to   successfully   execute   the   manufacturing,  warehousing  and  sales  processes  for  up  to  1000  MFLI  units  per  year.  

 

 

At   the   time   of   taking   the   screen   shots,   the  webshop  was   still   undergoing   tests   and  was   hosted   on   a   test  environment:  ziweb2/deploy/droducts/mfli  (the  test  environment  is  not  visible  to  the  outside  world)  

 

   

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Results  achieved  under  WP4  –  Training  and  Customer  Demos  

This  work  package  only  started  in  project  period  two.  Apart  from  LABS64,  who  are  not  planning  to  deploy  a  commercial  product  within  the  scope  of  DIMIDplus,  all  consortium  partners  prepared  and  executed  several  trainings  and  customer  demos.  

This   work   is   documented   in   detail   within   the   deliverables   “Training   Material”   and   “Report   on   Customer  Demos”.  Leaflets,  user  manuals  and  application  notes  can  be  found  as  well  on  the  respective  home  pages  of  the  partners.  Both  deliverables  of  this  work  package  were  submitted  on  time  or  with  a  minor  delay.  

D4.1  “Training  Material”  

All  training  material  required  to  conduct  trainings  and  to  perform  customer  demos  has  been  made  available.  The   deliverable   D4.1   “Training   Material”   has   been   submitted   in   Month   16   with   a   delay   of   one   month.  Although  this  deliverable  has  been  submitted,  new  training  material  is  constantly  being  generated.    The  table  bellows  shows  a  summary  of  the  training  material  that  has  been  made  available:    

ZURICH   CELLIX   AMPHASYS   CYTOGNOS  

Technical  Specifications   Technical  Specifications   AmphaZ30  User  Manual   Technical  Specifications  Quick  Start  Guide   Videos   AmphSoft  User  Manual   User  Manual  Tutorials       Quick  Start  Guide  Functional  Description       Webinars  Programmer  Manual        Application  Notes        Videos          

D4.2  “Report  on  Customer  Demos”  

The  product   launches   of   the   ETZEL   under   the   brand  name  MFLI   and   the  DIMID  device   for   pollen   analysis  under  the  brand  name  AMPHA  Z30  occurred  in  January  2015  and  April  2014,  respectively.  For  both  products,  ZURICH  and  AMPHASYS  did  numerous  customer  demonstrations,  either  during  product  fairs  or  directly  on-­‐site  with  customers.  For  the  DIMID  device  for  milk  analysis,  AMPHASYS  did  so  far  one  demonstration.  More  customer   demonstrations  will   follow   in   the   second   half   of   2015.   On   CELLIX   side,   the   focus   in   the   second  period  was   still  on  assay  validation.  Results  of   the  validation   stage  were  presented   to  numerous  potential  OEM  partners,  but  so  far  on  slides  only.  Demonstrations  with  the  actual  device  are  planned  to  occur  in  the  second  half  of  2015.  CYTOGNOS  demonstrated  DIMIDSoft  so  far  only  to  Consortium  internal  stakeholders.  

                               

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Results  achieved  under  WP5  –  Project  Management  

The  project  management  main  focus  was  on  tracking  the  overall  progress  of  the  project  towards  the  end  of  the  period.  The  critical  path  towards  the  end  goals  of  the  project  was  constantly  monitored  and  optimized  by  frequent   Skype   calls,   and   where   required,   by   F2F   meetings.   On   top   of   this,   a   common   platform   for  information   sharing   was   installed   (Confluence).   Work   shared   between   partners   was   tracked   and  documented  there.    While   some   of   the   project   tasks   could   be   executed   quite   independently   by   the   individual   partners   some  other  tasks  required  very  close  alignment  and  task  interfaces  between  partners  had  to  be  carefully  reviewed  and  constantly  optimized.  Most  challenging  was  the  final  integration  of  the  product  components  provided  by  ZURICH,  AMPHASYS  and  CYTOGNOS  into  the  final  version  of  the  DIMIDplus  haematology  of  CELLIX.  For  this  reasons,  dedicated  handover  Skype  calls  were  organized,   in  particular  between  CELLIX  and  ZURICH.  A   final  handover   of   the   ETZEL   electronic   unit   to  CELLIX  was   successfully   performed  beginning  of  November   2014  during  a  handover  and  training  session  taking  place  in  Dublin.    During  the  second  period  of  the  project,  more  and  more  focus  was  put  on  exploitation  and  on  dissemination,  which  is  reflected  in  the  list  of  deliverables  below.  All  deliverables  of  this  work  package  were  submitted  on  time  without  any  delay.  

D5.1  “Consortium  Agreement”    The  Consortium  Agreement  was  negotiated  at  the  very  beginning  of  the  DIMIDplus  project  and  signed  by  all  partners  in  December  2013.    D5.2  “Draft  PUDK  and  D5.3  Final  PUDK”  

Dissemination  of  knowledge  of  projects   funded  under  the  FP  7   is  an  obligation,  but  also  an  opportunity  to  increase   the   expected   impact   and   visibility   of   the   project   outcome.   For   a   demonstration   project   such   as  DIMIDplus,  where   final  products   ready  to  be  marketed  are  the  expected  outcome,  dissemination  activities  are  even  more   important   than   in  R&D  projects.  WP3  Commercialization  and  Marketing   and  WP4  Training  and   Customer   demos   of   the   present   project   are   already   including  major   dissemination   activities   and   are  therefore   just   briefly  mentioned   in   this   deliverable.   Besides   those,   the   deliverable   contains   an   IP   strategy  followed  in  this  project.  

D5.4  “Exploitation  Agreement”    One  of  the  key  deliverables  of  project  management  during  the  second  period  of  the  project  was  to  negotiate  and   finalize   the   exploitation   agreements   among   all   partners.   IP   and   OEM   partnership   agreements   not  detailed   in   the   Consortium   Agreement   had   to   be   clarified   and   resulted   in   complementing   exploitation  agreements.      

   

Page 24: PROJECT FINAL REPORT - CORDIS · 2016-08-18 · 4.1 Final&publishable&summaryreport& 4.1.1Executivesummary& 0 Based on the0 scientific0 results0of0 its0 predecessor0 project0 DIMID0GAo286692,

4.1.4  Potential  Impact  

The  DIMIDplus  project  has  bridged  the  gap  between  research  and  market  by  investing  a  joint  effort  of  five  SMEs  to  commercialize  a  high-­‐tech,  high-­‐potential   technology.    The  consortium  has  formed  a  highly   linked  business  model  focussing  on  six  business  opportunities:  

During  the  DIMIDplus  project,  the  five  partners  have  further  built  and  strengthened  their  core  competences:  

 

In  the  following  section,  the  achieved  commercial  results  of  all  SME  and  the  wider  impact  are  summarized:  

End  User  Markets

Potential

Zurich  Instruments

Impedance  Analyzer

EIS  Clustering  Software

Amphasys

Biology  Eng.Research

Lock-­‐in  Amplifier

Partner

AdditionalAssays

Seed    &PollenQuality

Physics  Research

Licensing/OEM

Cytognos

Cellix

Cellix ImmunoAssays

Dairy

Labs64

DIMIDplusGreenhouse  &Dairy  Device

DIMIDplusHaematologyDevice

1 2 3 4 5 6

Cellix Ltd., Unit 1, Longmile Business Park, Longmile Road, Dublin 12, Ireland

Tel: +353-1-4500-155 Fax: +353-1-4500-158 URL: www.cellixltd.com Email: [email protected]

- Page 1 -

Product Code 10 Pack: V8EP-800-120-02P10 Vena8 Endothelial+TM Biochip Updated Product Code 5 Pack: V8EP-800-120-02P5 Technical Note June 2011

Vena8 Endothelial+TM Biochip: For Cell - Primary Endothelial cell studies and

mimicking physiological flow

Features x 20x, 40x, 60x long working distance magnification microscopy.

x Wider channels for easy seeding of cells.

x Primary Endothelial cell monolayer obtained in 3 hours.

x Brightfield / Phase contrast / Fluorescent microscopy.

x Suitable for culturing wide range of Primary Endothelial cells.

x Suitable for whole blood and blood cells analysis (e.g. Leukocytes, platelets)

x Biochip plastic is optically clear permitting detailed microscopy studies.

x 0.05 – 200 dyne/cm2 shear stresses / shear flow rates easily obtained and controlled by the

MirusTM Nanopump and FlowAssayTM software.

x Shear stress / Shear flow rate may be preset to be incrementally increased during an assay.

x Real time imaging under flow conditions.

Vena8 Endothelial+TM Biochip

Vena8 Endothelial+TM Biochips contain 8 parallel enclosed microcapillaries for culturing Primary endothelial cells and continuous flow cell based assays. Primary endothelial cells are cultured and cell suspensions may then be injected using the MirusTM Nanopump which supports a range of shear stresses / shear flow rates for dynamic flow based assays. Vena8 Endothelial+TM Biochips are supplied in packs of 10, facilitating 80 experiments per pack.

Example:

Primary HUVECs cultured in Vena8 Endothelial+TM Biochip

Example: Adhesion of THP-1 monocytes at a shear stress of 0.5

dyne/cm2 to Primary HUVEC cultured in channel.

Illustration close-up: Cell-cell adhesion inside

Vena8 Endothelial+TM Biochip

Lock-in Amplifiers

Software & Signal

Processing

Microfluidic Chips

Pumps Applications

Cellix Ltd., Unit 1, Longmile Business Park, Longmile Road, Dublin 12, Ireland

Tel: +353-1-4500-155 Fax: +353-1-4500-158 URL: www.cellixltd.com Email: [email protected]

- Page 1 -

Product Code 10 Pack: V8EP-800-120-02P10 Vena8 Endothelial+TM Biochip Updated Product Code 5 Pack: V8EP-800-120-02P5 Technical Note June 2011

Vena8 Endothelial+TM Biochip: For Cell - Primary Endothelial cell studies and

mimicking physiological flow

Features x 20x, 40x, 60x long working distance magnification microscopy.

x Wider channels for easy seeding of cells.

x Primary Endothelial cell monolayer obtained in 3 hours.

x Brightfield / Phase contrast / Fluorescent microscopy.

x Suitable for culturing wide range of Primary Endothelial cells.

x Suitable for whole blood and blood cells analysis (e.g. Leukocytes, platelets)

x Biochip plastic is optically clear permitting detailed microscopy studies.

x 0.05 – 200 dyne/cm2 shear stresses / shear flow rates easily obtained and controlled by the

MirusTM Nanopump and FlowAssayTM software.

x Shear stress / Shear flow rate may be preset to be incrementally increased during an assay.

x Real time imaging under flow conditions.

Vena8 Endothelial+TM Biochip

Vena8 Endothelial+TM Biochips contain 8 parallel enclosed microcapillaries for culturing Primary endothelial cells and continuous flow cell based assays. Primary endothelial cells are cultured and cell suspensions may then be injected using the MirusTM Nanopump which supports a range of shear stresses / shear flow rates for dynamic flow based assays. Vena8 Endothelial+TM Biochips are supplied in packs of 10, facilitating 80 experiments per pack.

Example:

Primary HUVECs cultured in Vena8 Endothelial+TM Biochip

Example: Adhesion of THP-1 monocytes at a shear stress of 0.5

dyne/cm2 to Primary HUVEC cultured in channel.

Illustration close-up: Cell-cell adhesion inside

Vena8 Endothelial+TM Biochip

Cellix Ltd., Unit 1, Longmile Business Park, Longmile Road, Dublin 12, Ireland

Tel: +353-1-4500-155 Fax: +353-1-4500-158 URL: www.cellixltd.com Email: [email protected]

- Page 1 -

Product Code 10 Pack: V8EP-800-120-02P10 Vena8 Endothelial+TM Biochip Updated Product Code 5 Pack: V8EP-800-120-02P5 Technical Note June 2011

Vena8 Endothelial+TM Biochip: For Cell - Primary Endothelial cell studies and

mimicking physiological flow

Features x 20x, 40x, 60x long working distance magnification microscopy.

x Wider channels for easy seeding of cells.

x Primary Endothelial cell monolayer obtained in 3 hours.

x Brightfield / Phase contrast / Fluorescent microscopy.

x Suitable for culturing wide range of Primary Endothelial cells.

x Suitable for whole blood and blood cells analysis (e.g. Leukocytes, platelets)

x Biochip plastic is optically clear permitting detailed microscopy studies.

x 0.05 – 200 dyne/cm2 shear stresses / shear flow rates easily obtained and controlled by the

MirusTM Nanopump and FlowAssayTM software.

x Shear stress / Shear flow rate may be preset to be incrementally increased during an assay.

x Real time imaging under flow conditions.

Vena8 Endothelial+TM Biochip

Vena8 Endothelial+TM Biochips contain 8 parallel enclosed microcapillaries for culturing Primary endothelial cells and continuous flow cell based assays. Primary endothelial cells are cultured and cell suspensions may then be injected using the MirusTM Nanopump which supports a range of shear stresses / shear flow rates for dynamic flow based assays. Vena8 Endothelial+TM Biochips are supplied in packs of 10, facilitating 80 experiments per pack.

Example:

Primary HUVECs cultured in Vena8 Endothelial+TM Biochip

Example: Adhesion of THP-1 monocytes at a shear stress of 0.5

dyne/cm2 to Primary HUVEC cultured in channel.

Illustration close-up: Cell-cell adhesion inside

Vena8 Endothelial+TM Biochip

Cellix Ltd., Unit 1, Longmile Business Park, Longmile Road, Dublin 12, Ireland

Tel: +353-1-4500-155 Fax: +353-1-4500-158 URL: www.cellixltd.com Email: [email protected]

- Page 1 -

Product Code 10 Pack: V8EP-800-120-02P10 Vena8 Endothelial+TM Biochip Updated Product Code 5 Pack: V8EP-800-120-02P5 Technical Note June 2011

Vena8 Endothelial+TM Biochip: For Cell - Primary Endothelial cell studies and

mimicking physiological flow

Features x 20x, 40x, 60x long working distance magnification microscopy.

x Wider channels for easy seeding of cells.

x Primary Endothelial cell monolayer obtained in 3 hours.

x Brightfield / Phase contrast / Fluorescent microscopy.

x Suitable for culturing wide range of Primary Endothelial cells.

x Suitable for whole blood and blood cells analysis (e.g. Leukocytes, platelets)

x Biochip plastic is optically clear permitting detailed microscopy studies.

x 0.05 – 200 dyne/cm2 shear stresses / shear flow rates easily obtained and controlled by the

MirusTM Nanopump and FlowAssayTM software.

x Shear stress / Shear flow rate may be preset to be incrementally increased during an assay.

x Real time imaging under flow conditions.

Vena8 Endothelial+TM Biochip

Vena8 Endothelial+TM Biochips contain 8 parallel enclosed microcapillaries for culturing Primary endothelial cells and continuous flow cell based assays. Primary endothelial cells are cultured and cell suspensions may then be injected using the MirusTM Nanopump which supports a range of shear stresses / shear flow rates for dynamic flow based assays. Vena8 Endothelial+TM Biochips are supplied in packs of 10, facilitating 80 experiments per pack.

Example:

Primary HUVECs cultured in Vena8 Endothelial+TM Biochip

Example: Adhesion of THP-1 monocytes at a shear stress of 0.5

dyne/cm2 to Primary HUVEC cultured in channel.

Illustration close-up: Cell-cell adhesion inside

Vena8 Endothelial+TM Biochip

IVD Regulations

DIMID!–!GA!n°!606100! ! D1.1!!

! 4!

2. ETZEL%Device%Demonstration!

!

2.1! ETZEL!Product!Pictures!

!Figure!1:!MFLI!Product!

2.2! ETZEL!Demonstration!Protocol!

This!protocol!describes!the!demonstration!of!the!ETZEL!standPalone!version.!The!ETZEL!OEM!version!will!be!demonstrated!as!part!of!the!DIMIDplus!device!for!haematology.!!The! demonstration! will! focus! on! a! typical! measurement! application.! The! impedance! characteristic! of! a!resonator! is!shown!for!the!frequency!range!from!100!Hz!to!5!MHz.!The!sweeper! function!of! the!ETZEL! is!used!for!this.!The!entire!demonstration!will!be!shown!on!an!iPad!directly!connected!to!the!ETZEL!via!WLAN.!!Protocol!Step1:!The!ETZEL!(commercial!name!MFLI)!is!taken!out!of!its!package!!Protocol!Step!2:!The!ETZEL!is!connected!to!power!!Protocol!Step!3:!The!USB!WLAN!dongle!is!inserted!into!the!USB!Host!connector!!Protocol!Step!4:!The!iPad!is!turned!on!and!its!Web!Browser!is!started!!Protocol!Step!5:!The!browser!connects!to!ETZEL,!which!is!configured!as!a!WLAN!hotspot!!Protocol!Step!6:!The!measurement!software!LabOne!is!started!and!opened!in!a!browser!window!!Protocol!Step!7:!The!device!under!test!(DUT)!is!connected!to!the!ETZEL!(a!resonator)!!Protocol!Step!8:!Current!input!and!voltage!output!of!the!ETZEL!are!configured!!Protocol!Step!9:!The!Sweeper!Tab!of!the!LabOne!UI!is!launched!!Protocol!Step!10:!The!impedance!characteristic!of!the!resonator!is!plotted!!The!demonstration!itself!will!take!place!at!the!final!DIMIDplus!review!in!Dublin,!May!28,!2015.!

Cellix Ltd., Unit 1, Longmile Business Park, Longmile Road, Dublin 12, Ireland

Tel: +353-1-4500-155 Fax: +353-1-4500-158 URL: www.cellixltd.com Email: [email protected]

- Page 1 -

Product Code 10 Pack: V8EP-800-120-02P10 Vena8 Endothelial+TM Biochip Updated Product Code 5 Pack: V8EP-800-120-02P5 Technical Note June 2011

Vena8 Endothelial+TM Biochip: For Cell - Primary Endothelial cell studies and

mimicking physiological flow

Features x 20x, 40x, 60x long working distance magnification microscopy.

x Wider channels for easy seeding of cells.

x Primary Endothelial cell monolayer obtained in 3 hours.

x Brightfield / Phase contrast / Fluorescent microscopy.

x Suitable for culturing wide range of Primary Endothelial cells.

x Suitable for whole blood and blood cells analysis (e.g. Leukocytes, platelets)

x Biochip plastic is optically clear permitting detailed microscopy studies.

x 0.05 – 200 dyne/cm2 shear stresses / shear flow rates easily obtained and controlled by the

MirusTM Nanopump and FlowAssayTM software.

x Shear stress / Shear flow rate may be preset to be incrementally increased during an assay.

x Real time imaging under flow conditions.

Vena8 Endothelial+TM Biochip

Vena8 Endothelial+TM Biochips contain 8 parallel enclosed microcapillaries for culturing Primary endothelial cells and continuous flow cell based assays. Primary endothelial cells are cultured and cell suspensions may then be injected using the MirusTM Nanopump which supports a range of shear stresses / shear flow rates for dynamic flow based assays. Vena8 Endothelial+TM Biochips are supplied in packs of 10, facilitating 80 experiments per pack.

Example:

Primary HUVECs cultured in Vena8 Endothelial+TM Biochip

Example: Adhesion of THP-1 monocytes at a shear stress of 0.5

dyne/cm2 to Primary HUVEC cultured in channel.

Illustration close-up: Cell-cell adhesion inside

Vena8 Endothelial+TM Biochip

Page 25: PROJECT FINAL REPORT - CORDIS · 2016-08-18 · 4.1 Final&publishable&summaryreport& 4.1.1Executivesummary& 0 Based on the0 scientific0 results0of0 its0 predecessor0 project0 DIMID0GAo286692,

Commercialization  Opportunity  1:  ZURICH  –  Physics  Research    

The   ETZEL   has   been   commercialized   and   launched   under   the   name   MFLI   as  instrument  dedicated  to  Physics  Research  on  January  30,  2015.  The  product  can  be  found  and  ordered  under  http://www.zhinst.com/products/mfli.  The  MFLI  sets   the  new   standard   for   measurements   in   the   medium   and   low   frequency   range   and   is  available  in  two  versions:  DC  to  500  kHz  and  DC  to  5  MHz  (an  upgrade  from  500  kHz  to   5   MHz   is   possible   later).   The   MFLI   combines   superior   performance   with   the  outstanding   LabOne®   toolset.   The   embedded   data   and   web   servers   allow  straightforward  connection  to  any  device  running  a  web  browser.  

Typical  Physics  applications  are:  

•   Optical  chopper  applications  •   Pulsed  laser  applications  (e.g.  high  power  lasers)  •   Materials  research  •   Quantum-­‐  and  Nano-­‐electronics  •   Materials  research  •   Scanning  tunnelling  microscopy  •   Low  temperature  physics  •   Impedance  spectroscopy  •   Seismic  measurements    

Commercialization  Opportunity  2:  ZURICH  –  Biology  Engineering  and  Research  

The  MFLI  is  commercially  available  and  can  be  purchased  in  a  5  MHz  and  a  500  kHz  version.  Customers  that  initially   purchased   a   500   kHz   version   can   upgrade   their   device   later   to   5  MHz  by   purchasing   the  MF-­‐F5M  frequency   extension   option.   Furthermore,   a   MF-­‐MD   multi-­‐demodulator   option   is   available.   Both   options  together   turn   the   MFLI   into   a   powerful   instrument   for   impedance   spectroscopy   serving   the   biology  engineering  and  research  markets.  

Socio-­‐economic  Impact  and  wider  societal  implications  (Opportunity  1  &  2):  

• Creation  of  15  job  opportunities  directly  at  Zurich  Instruments  within  the  next  3  years  • Creation  of  up  to  25  job  opportunities  with  suppliers  of  Zurich  Instruments  within  the  next  5  years  

Dissemination  Activities  (see  Annex  for  more  details)::  

• Strong  representation  at  several  exhibitions  during  the  product  launch  in  February  and  March  2015  • Press  releases  • Videos  

Exploitation  Results  (see  Annex  for  more  details):  

• Two  commercially  available  products  MFLI  500  kHz  and  MFLI  5  MHz.    • LabOne  measurement  software,  trademark  submitted  and  registered  in  September  2014.  

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Commercialization  Opportunity  3:  AMPHASYS  –  Seed  and  Pollen  Analysis  

The   AMPHA   Z30   is   commercially   available   and   can   be   purchased   under  http://www.amphasys.com.   This   instrument   is   being   used   for   many   research  applications  like  bacterial  analysis,  apoptosis  or  cell  differentiation  (cancer  and  stem  cell   research)   as   an   alternative   to   conventional,   fluorescence-­‐based   flow  cytometers.  Besides   the  classical   research  applications,  AMPHASYS   is  also   focusing  its  activities  on  industrial  applications,  where  the  company  sees  a  huge  potential  for  the  technology.  

The   reliable   determination   of   pollen   quality   is   a   key   success   factor   in   the   seed   production   process.  Experiments  show  a  clear  correlation  between  the  viability  (also  called  vitality)  of  pollen  used  for  pollination  and   the   obtained   seed   yield.   External   factors   such   as   light,   rain,   temperature   or   chemical   agents   may  influence  pollen  viability.  Amphasys  provides  an  easy  method  to  monitor  pollen  viability  and  thus  a  powerful  tool  to  optimize  the  plant  breeding  and  seed  production  process.  This   is  particularly   important   if   laborious  manual   steps   are   involved   and   if   pollen  needs   to   be   stored  or   transported   from  one   site   to   another.   The  technology  can  be  used  on-­‐site,  directly  in  or  near  the  greenhouse.  

The  product   has   been   launched   in  April   2014.  AMPHASYS  has   received   several   orders   and   is   shipping   the  device  to  customers.  

Commercialization  Opportunity  4:  AMPHASYS  –  Dairy  

For  the  milk  industry,  the  quality  of  raw  milk  is  a  major  concern.  High  somatic  cell  counts  mainly  caused  by  bacterial   infections  and  bacterial  contamination  caused  by   insufficient  equipment  sanitation  or   insufficient  cleansing  of  the  cow's  udder  and  teats  have  an  adverse  impact  on  the  milk  products.  Amphasys’  technology  allows  a  direct  determination  of  the  somatic  cell  count  in  untreated  raw  milk.  The  product  will  be  launched  in  the  second  half  of  2015.  AMPHASYS  is  in  contact  with  several  customers  interested  in  the  dairy  application  and  first  orders  are  likely  to  materialize  in  the  end  of  2015.  

Socio-­‐economic  Impact  and  wider  societal  implications  (Opportunity  3  &  4):  

• Creation  of  several  job  opportunities  directly  at  AMPHASYS  and  as  well  at  their  suppliers  • Increased  efficiency  of  seed  and  crop  production  through  availability  of  a  new  technology  that  can  

reliably  measure  pollen  viability  • Improved  herd  management   for   farmers   by   efficient   and   cost   effective  monitoring  of   the   somatic  

cell  count  of  raw  milk  

Dissemination  Activities  (see  Annex  for  more  details):  

• Press  releases  • Conferences  • Videos  

Exploitation  Results  (see  Annex  for  more  details):  

• Commercially  available  product  AMPHA  Z30  • Single  cell  analysis  software  AMPHAsoft    

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Commercialization  Opportunity  5:    CELLIX  -­‐  Non-­‐IVD  Haematology  applications  

The  DIMIDplus  portable  device  for  haematology  may  be  marketed  to  the  non-­‐IVD  scientific  research  market.  This  business  case  has  not  been  actively  pursued  within  the  DIMIDplus,  but  remains  a  valid  business  option.  

 

Commercialization  Opportunity  6:    CELLIX  -­‐  Haematology  diagnostics  (OEM)  

The  DIMIDplus   portable   device   for   haematology   diagnostics   is   available  for   demonstration   to   research   customers   and   potential   OEM   partners.  Due   to   its   complexity,   this   commercialization   opportunity   has   received  the   highest   attention   within   the   Consortium,   as   it   required   the   close  cooperation  of  all  partners.  CELLIX  has  entered  negotiations  on  deploying  the  new  technology  to  several  diagnostics  partners.  

 

Socio-­‐economic  Impact  and  wider  societal  implications  (Opportunity  6):  

• Strongly  depending  of  future  collaboration  with  potential  OEM  partners  • Full   scale-­‐up   and   commercialization   of   a   portable   point-­‐of-­‐care   device   will   create   a   significant  

number  of  job  opportunities  at  CELLIX  itself,  at  its  OEM  partner  and  at  the  corresponding  suppliers  • The   cost   advantage   over   traditional   optical   based   haematology   analysers   combined   with   the  

portability   of   the   device   can   have   a   significant   impact   on   personal   health   coverage   for   emerging  markets  and  regions  with  reduced  access  to  hospitals.  

Dissemination  Activities  (see  Annex  for  more  details):  

• Presentation  of  the  technology  at  various  conferences,  e.g.  uTAS  in  Texas,  October  2014.  • Videos  

Exploitation  Results  (see  Annex  for  more  details):  

• Available  demonstrator  for  haematology  diagnostic  applications  targeting  RBC  and  WBC  assays  

 

 

Cellix Ltd., Unit 1, Longmile Business Park, Longmile Road, Dublin 12, Ireland

Tel: +353-1-4500-155 Fax: +353-1-4500-158 URL: www.cellixltd.com Email: [email protected]

- Page 1 -

Product Code 10 Pack: V8EP-800-120-02P10 Vena8 Endothelial+TM Biochip Updated Product Code 5 Pack: V8EP-800-120-02P5 Technical Note June 2011

Vena8 Endothelial+TM Biochip: For Cell - Primary Endothelial cell studies and

mimicking physiological flow

Features x 20x, 40x, 60x long working distance magnification microscopy.

x Wider channels for easy seeding of cells.

x Primary Endothelial cell monolayer obtained in 3 hours.

x Brightfield / Phase contrast / Fluorescent microscopy.

x Suitable for culturing wide range of Primary Endothelial cells.

x Suitable for whole blood and blood cells analysis (e.g. Leukocytes, platelets)

x Biochip plastic is optically clear permitting detailed microscopy studies.

x 0.05 – 200 dyne/cm2 shear stresses / shear flow rates easily obtained and controlled by the

MirusTM Nanopump and FlowAssayTM software.

x Shear stress / Shear flow rate may be preset to be incrementally increased during an assay.

x Real time imaging under flow conditions.

Vena8 Endothelial+TM Biochip

Vena8 Endothelial+TM Biochips contain 8 parallel enclosed microcapillaries for culturing Primary endothelial cells and continuous flow cell based assays. Primary endothelial cells are cultured and cell suspensions may then be injected using the MirusTM Nanopump which supports a range of shear stresses / shear flow rates for dynamic flow based assays. Vena8 Endothelial+TM Biochips are supplied in packs of 10, facilitating 80 experiments per pack.

Example:

Primary HUVECs cultured in Vena8 Endothelial+TM Biochip

Example: Adhesion of THP-1 monocytes at a shear stress of 0.5

dyne/cm2 to Primary HUVEC cultured in channel.

Illustration close-up: Cell-cell adhesion inside

Vena8 Endothelial+TM Biochip

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 4.1.5  Public  Website  and  Contact  Details  

The  DIMIDplus  Website  has  been  continuously  updated  during  the  project   including  a  new  front  page  with  images  for  pollen  and  dairy  applications,  new  videos,  updated  partner’s  events  participation,  press  releases  and  news.  Following   the  EC   recommendations  FP  7th   logo  has  been  substituted  by   the  EU  emblem  on   the  DIMIDplus  website.  The  home  page  of  the  project  is  found  under:  http://www.dimid-­‐project.eu.    

 The  website  maintains  a  simple  and  clear  structure  presenting  the  outcomes  of  the  DIMIDplus  project  and  the  future  marketable  products.  During  the  entire  project,  new  DIMIDplus  brochure,  posters  and  logo  have  been   created   with   a   new   refreshing   aspect   focused   on   benefits   and   broad   potential   applications   of   the  impedance  flow  cytometry.    DIMIDplus  brochure  and  posters  are  available  at  the  home  page.    

Contacts  of  the  project  partners  are  listed  below:  

ZURICH  INSTRUMENTS  AG  

Coordinator  • Adrian  Messmer,  VP  R&D  • Email:  [email protected]    

CELLIX  LIMITED     Partner  • Vivienne  Williams,  CEO  

Email:  [email protected]    

CYTOGNOS  SL   Partner  • Álvaro  Rodríguez,  CFO  

Email:  [email protected]  

AMPHASYS  AG   Partner  • Marco  Di  Berardino,  Executive  Partner  • Email:  [email protected]  

LABS64  GMBH   Partner  • Konstantin  Korotkov,  CEO  • Email:  [email protected]