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Lab on a chip …

             or

      chip in the lab?

           Laurent A. FRANCIS
                     
                                      
  Université catholique de Louvain (UCL)
ICTEAM/Electrical Engineering Department   
   Sensors, Microsystems and Actuators 

          Laboratory of Louvain
                     
                     
      Research Talks Oct. 10, 2011

       Louvain-la-Neuve, Belgium
How do you
 feel today ?
       
       
       
       
       
       
       
       
       
       
Far future ???
                  2
1 ml
              Needles in the hay




   aM    fM     pM       nM      µM      mM      M
   103   106    109     1012     1015    1018   1021
          # molecules/ml for typical samples

                                                       3
Size does matter!
             	

             	

                                                           	

                                                           	

             	

                                           	

        Microfluidics	

                           Conventional fluidics	



nm	

               µm	

                    mm	

                 m	


            aL	

    fL	

   pL	

   nL	

   µL	

          L	

            µM      nM       pM      fM      aM




                                                                      4
Bacteria              DNA            Sample screening
Raw sample          Cancer cells           RNA              Hydridization
                      Etc…                proteins          Sequencing

          Cell separation                         Amplification
                                 Lysis
          Centrifugation                          Polymerase
                               Purification
             Filtering                           chain reaction




                                  PCR	

                  Chiron Tigris 	

   Cell lysis	

                                      for Blood screening	

                            Qiagen Symphony	

                                 5
6
Chip	
  Cartridge	
  
Glass	
  Microreactor	
  	
  
made	
  by	
  Micronit	
  Microfluidics	
  




                                             7
Lab on a Chip - Applications
                           
                                   Point of Care  
                                         
                                    Diagnostics 
                                         
                                     Pathogens 
                                         
                                  Drugs discovery    
                                         
                                Environment control    
                                         
                                  Terrorist threat  
                                         
                               Forensics & Genomics      

                                                         8
µ-FLUIDICS                 DNA	

              PROTEINS	

             NEURONS	

   CELLS	

          ASSAY




         ELECTRONICS



                                                                                                         9
Inspired from Introduction to bioanalytical sensors. A.J. Cunningham. Wiley: 1998
PUMPING
                          ELECTROKINETIC	

           MECHANICAL	

           ACOUSTIC	

     CENTRIFUGAL	




          µ-FLUIDICS                 DNA	

              PROTEINS	

             NEURONS	

         CELLS	

          ASSAY


         (BIO)CHEMICAL                              SELECTIVE RECOGNITION 	

                                                               EVENT	



         PHYSICAL




         ELECTRONICS



                                                                                                               10
Inspired from Introduction to bioanalytical sensors. A.J. Cunningham. Wiley: 1998
PUMPING
                          ELECTROKINETIC	

              MECHANICAL	

        ACOUSTIC	

     CENTRIFUGAL	




          µ-FLUIDICS                 DNA	

                PROTEINS	

           NEURONS	

         CELLS	

          ASSAY


         (BIO)CHEMICAL                              SELECTIVE RECOGNITION 	

                                                            EVENT	



         PHYSICAL

                                                              ELECTROMAGNETIC OR	

                   ELECTROCHEMICAL	

                                                             THERMAL	

                                                               ELECTROMECHANICAL	





          AMPERO-	

    CONDUCTO-      POTENTIO-
                          METRIC	

        METRIC	

                                                                 OPTICAL	

 ACOUSTIC	

           METRIC	





         ELECTRONICS
                                              RESPONSE  PROCESSING  READOUT	




                                                                                                               11
Inspired from Introduction to bioanalytical sensors. A.J. Cunningham. Wiley: 1998
When	
  Microtech	
  met	
  Biotech	
  




    Interface	
  –	
  smart	
  coa:ngs	
  /	
  Self-­‐Assembled	
  Monolayers	
  


                               Transducer	
  



                                                                                    12
Biosensors	
  	
  Immunosensors	
  


                                    http://www.microsens.ch	





•    Electrical/Electrochemical	
   •                            Op6cal	
  	
                               •     Acous6c	
  	
  
      –  Ion	
  Sensi:ve	
  FET	
  (pH)	
                –  Surface	
  Plasmon	
  Resonance	
  	
                  –  Quartz	
  Crystal	
  Microbalance	
  	
  
                                                         –  Waveguides	
                                           –  Surface Acoustic Wave	
  
      –  Interdigitated	
  electrodes	
  
          Surface	
  func6onaliza6on	
  –	
  	
  In-­‐liquid	
  opera6on	
  –	
  Affinity	
  binding	
  –	
  	
  Surface	
  (volume)	
  sensing	
  
                                                                                                                                                       13	
  
Research to create an autonomous micro-chemistry lab involves
                    exploring science in a micro-domain where properties can run
                                     counter to normal intuition 
                            (Sandia National Laboratories, April 23, 1998) 	





Photo by Randy Montoya	




                               In 1998: In five to 10 years, future devices should be able 
                                 to simultaneously identify hundreds of liquids and gases. 	

 14
Pros and cons of LOC
     Fast!          Fast evaporation

Small volumes        Concentration?

  Low power           Laminar flow

  Ease of use          Poor scaling

 Field-portable   Large dimension wrt Si

Cheap materials        Packaging
                                           15
Worldwide market for microfluidic technologies




      In 2007              MEMS market                6 Billions $
                           Consumer electronics     160 Billions $

Source BCC, Inc.	

http://www.bccresearch.com/report/SMC036B.html	

                    16
Research @UCL - Bacteria on IDAMOS
     Large capacitance shifts due to mirror charges




                                               50 fF/bact.
                                               10 nS/bact.
Sensor surface 200 x 200 um2



                                                              17
Research @UCL - Injection molding of COC
                      COC – Cyclic Olefin Copolymer




The several advantages of COC
•  Optically transparent (cut off at 320 nm)
•  High Tg (170°C), comparable to PMMA, much better than PDMS
•  High chemical resistance
•  Low non-specific binding with biochemical species
•  Processed by injection molding  high throughput/low cost
      Injection molding replica from Si mold in PMMA and COC UCL/SIRRIS Wallonie

                                                                                   18
The 10 major hurdles
                                         
         Device - related 
                              People - related 
    1.  Counter-intuitive                          1.  Low critical mass
        operation principles
                      2.  Lack of 

    2.  Hybrid technologies,                           cross-fertilization
        not standard to IC                         3.  Missing confidence
        microfabrication
                                                   4.  Sharing protocols
    3.  Low signal/noise
                                                   5.  Regulations, norms and
    4.  Reliability issue
                             market constraints
    5.  Lack of true autonomy



Picture http://caitlinlawrence.deviantart.com	

                              19
From Chip in the lab to Lab on a Chip

You have                
an idea?
                       •  Interdisciplinary platform
                          with practicians, engineers
                          in various disciplines,
                          chemists, economists, …

                       •  Educationnal aspects?!

                       •  Not one but many
                          prototypes as a key to
                          success!

                       •  Large(r) investments and
                          ventures 

                                                   20
Thank you for your attention!!




UCL Microsystems Chair – SMALL research group
Contact Laurent.Francis@uclouvain.be
Website http://www.uclouvain.be/chair-microsystems

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ResearchTalks Vol. 2 - Lab on a chip ... or chip in the lab ?

  • 1. Lab on a chip …
 or
 chip in the lab? Laurent A. FRANCIS Université catholique de Louvain (UCL) ICTEAM/Electrical Engineering Department Sensors, Microsystems and Actuators 
 Laboratory of Louvain Research Talks Oct. 10, 2011
 Louvain-la-Neuve, Belgium
  • 2. How do you feel today ? Far future ??? 2
  • 3. 1 ml Needles in the hay aM fM pM nM µM mM M 103 106 109 1012 1015 1018 1021 # molecules/ml for typical samples 3
  • 4. Size does matter! Microfluidics Conventional fluidics nm µm mm m aL fL pL nL µL L µM nM pM fM aM 4
  • 5. Bacteria DNA Sample screening Raw sample Cancer cells RNA Hydridization Etc… proteins Sequencing Cell separation Amplification Lysis Centrifugation Polymerase Purification Filtering chain reaction PCR Chiron Tigris Cell lysis for Blood screening Qiagen Symphony 5
  • 6. 6
  • 7. Chip  Cartridge   Glass  Microreactor     made  by  Micronit  Microfluidics   7
  • 8. Lab on a Chip - Applications Point of Care Diagnostics Pathogens Drugs discovery Environment control Terrorist threat Forensics & Genomics 8
  • 9. µ-FLUIDICS DNA PROTEINS NEURONS CELLS ASSAY ELECTRONICS 9 Inspired from Introduction to bioanalytical sensors. A.J. Cunningham. Wiley: 1998
  • 10. PUMPING ELECTROKINETIC MECHANICAL ACOUSTIC CENTRIFUGAL µ-FLUIDICS DNA PROTEINS NEURONS CELLS ASSAY (BIO)CHEMICAL SELECTIVE RECOGNITION EVENT PHYSICAL ELECTRONICS 10 Inspired from Introduction to bioanalytical sensors. A.J. Cunningham. Wiley: 1998
  • 11. PUMPING ELECTROKINETIC MECHANICAL ACOUSTIC CENTRIFUGAL µ-FLUIDICS DNA PROTEINS NEURONS CELLS ASSAY (BIO)CHEMICAL SELECTIVE RECOGNITION EVENT PHYSICAL ELECTROMAGNETIC OR ELECTROCHEMICAL THERMAL ELECTROMECHANICAL AMPERO- CONDUCTO- POTENTIO- METRIC METRIC OPTICAL ACOUSTIC METRIC ELECTRONICS RESPONSE  PROCESSING  READOUT 11 Inspired from Introduction to bioanalytical sensors. A.J. Cunningham. Wiley: 1998
  • 12. When  Microtech  met  Biotech   Interface  –  smart  coa:ngs  /  Self-­‐Assembled  Monolayers   Transducer   12
  • 13. Biosensors    Immunosensors   http://www.microsens.ch •  Electrical/Electrochemical   •  Op6cal     •  Acous6c     –  Ion  Sensi:ve  FET  (pH)   –  Surface  Plasmon  Resonance     –  Quartz  Crystal  Microbalance     –  Waveguides   –  Surface Acoustic Wave   –  Interdigitated  electrodes   Surface  func6onaliza6on  –    In-­‐liquid  opera6on  –  Affinity  binding  –    Surface  (volume)  sensing   13  
  • 14. Research to create an autonomous micro-chemistry lab involves exploring science in a micro-domain where properties can run counter to normal intuition (Sandia National Laboratories, April 23, 1998) Photo by Randy Montoya In 1998: In five to 10 years, future devices should be able to simultaneously identify hundreds of liquids and gases. 14
  • 15. Pros and cons of LOC Fast! Fast evaporation Small volumes Concentration? Low power Laminar flow Ease of use Poor scaling Field-portable Large dimension wrt Si Cheap materials Packaging 15
  • 16. Worldwide market for microfluidic technologies In 2007 MEMS market 6 Billions $ Consumer electronics 160 Billions $ Source BCC, Inc. http://www.bccresearch.com/report/SMC036B.html 16
  • 17. Research @UCL - Bacteria on IDAMOS Large capacitance shifts due to mirror charges 50 fF/bact. 10 nS/bact. Sensor surface 200 x 200 um2 17
  • 18. Research @UCL - Injection molding of COC COC – Cyclic Olefin Copolymer The several advantages of COC •  Optically transparent (cut off at 320 nm) •  High Tg (170°C), comparable to PMMA, much better than PDMS •  High chemical resistance •  Low non-specific binding with biochemical species •  Processed by injection molding  high throughput/low cost Injection molding replica from Si mold in PMMA and COC UCL/SIRRIS Wallonie 18
  • 19. The 10 major hurdles Device - related People - related 1.  Counter-intuitive 1.  Low critical mass operation principles 2.  Lack of 
 2.  Hybrid technologies, cross-fertilization not standard to IC 3.  Missing confidence microfabrication 4.  Sharing protocols 3.  Low signal/noise 5.  Regulations, norms and 4.  Reliability issue market constraints 5.  Lack of true autonomy Picture http://caitlinlawrence.deviantart.com 19
  • 20. From Chip in the lab to Lab on a Chip You have an idea? •  Interdisciplinary platform with practicians, engineers in various disciplines, chemists, economists, … •  Educationnal aspects?! •  Not one but many prototypes as a key to success! •  Large(r) investments and ventures 20
  • 21. Thank you for your attention!! UCL Microsystems Chair – SMALL research group Contact Laurent.Francis@uclouvain.be Website http://www.uclouvain.be/chair-microsystems