Contents. Microfluidics - Jens Ducrée Flow Control 1

Contents 1. Introduction 2. Fluids 3. Physics of Microfluidic Systems 4. Microfabrication Technologies 5. Flow Control 6. Micropumps 7. Sensors 8. Ink-Jet Technology 9. Liquid Handling 10.Microarrays 11.Microreactors 12.Analytical Chips 13.Particle-Laden Fluids a. Measurement Techniques b. Fundamentals of Biotechnology c. High-Throughput Screening Microfluidics - Jens Ducrée Flow Control 1

1. Check Valves 2. Fixed-Geometry Valves 3. Actuation Principles 4. Active Micro-Valves 5. Fluerics 5. Flow Control Microfluidics - Jens Ducrée Flow Control 2

1. Check Valves 2. Fixed-Geometry Valves 3. Actuation Principles 4. Active Micro-Valves 5. Fluerics 5. Flow Control Microfluidics - Jens Ducrée Flow Control 3

5.1. Definition Passive Valve Definition: Flow rectifier Controlled by hydrodynamic pressure (p 1 p 2 ) Built up by flow itself Interplay with geometrical structure Characteristics: valve seat flow channel silicon Flow rate / leakage Hydrodynamic actuation force F = p A p 2 Hydraulic capacitance Resonance curve valve membrane p 1 0,5 mm Microfluidics - Jens Ducrée Flow Control 4

5.1. Types of Passive Valves Note: Different effective areas A for force F = p A generated by pressure p Microfluidics - Jens Ducrée Flow Control 5

5.1. Check Valves 1. Membrane Valves 2. Flap Valves 3. Bivalvular Valves 4. Leakage Microfluidics - Jens Ducrée Flow Control 6

5.1.1. Membrane Valves Components: Peripherally fixed membrane Central hole Advantages: High force due to large effective area for pressure valve seat flow channel silicon Drawbacks: Large size Large capacitance Large dead volume valve membrane 0,5 mm Microfluidics - Jens Ducrée Flow Control 7

5.1.1. Theoretical Background Calculation of flow for gases Main impact factor Smallest cross section A min h < A/U A min = h s h > A/U A min = A Expansion flow through nozzle m M p A min 2 v A,2 1 1 Microfluidics - Jens Ducrée Flow Control 8

5.1.1. Membrane Valves Flow Rate Gap opening; pressure-dependent s ~ p Flow through narrow gap (laminar friction / viscosity prevails) I V ~ p 4 Flow through short constriction (e.g.: b < s) (conversion of potential to kinetic energy prevails) V ~ p 3/2 Microfluidics - Jens Ducrée Flow Control 9

5.1.1. Flow Rate Gap height h Circumference s Pressure surface A valve seat flow channel silicon Elastic module k elast valve membrane 0,5 mm Microfluidics - Jens Ducrée Flow Control 10

5.1.1. Theoretical Background Enhancement of flow (A min = U s) valve opening Ventilöffnung sealing Dichtkante Einlaufkanal inlet channel Auslaufkanal outlet channel quadratic rectangular meander-like Microfluidics - Jens Ducrée Flow Control 11

5.1.1. Construction Principles Microfluidics - Jens Ducrée Flow Control 12

5.1.1. Membrane Valves - Fabrication a b c o 54,7 d a 3 a 2 a 1 e a 4 a 5 f g Microfluidics - Jens Ducrée Flow Control 13

5.1.1. Membrane Valves Components: Peripherally fixed membrane Central hole Advantages: High force due to large effective area for pressure Drawbacks: Large size Large capacitance Large dead volume Microfluidics - Jens Ducrée Flow Control 14

5.1.1. Theoretical Background Structural mechanics l a A Restoring force by elastic support of valve plate A F el1 4 2 2 3 E ba,1 4 ba,1 ba,2 ba,2 ha z 2 Vp 1 b b l 3 3 a,1 a,2 a ba,1 Schnitt A-A ha ba,2 Microfluidics - Jens Ducrée Flow Control 15

5.1.1. Membrane Valves Gap flow (b > h) Constriction flow (b < h) 4000 10000 Flux [µl/min] 3500 3000 2500 2000 1500 1000 500 Type M1; a 3 = 15 µm; a 5 = 75 µm valve with broad valve seat Flux [µl/min] 8000 6000 4000 2000 Type M1; a 3 = 9 µm; a 5 = 5 µm valve with narrow valve seat 0 0 50 100 150 200 Pressure [hpa] gap-like 0 0 20 40 60 80 100 120 Pressure [hpa] constriction-like Microfluidics - Jens Ducrée Flow Control 16

5.1.1. Hydraulic Capacitance Microfluidics - Jens Ducrée Flow Control 17

5.1. Check Valves 1. Membrane Valves 2. Flap Valves 3. Bivalvular Valves 4. Leakage Microfluidics - Jens Ducrée Flow Control 18

5.1.2. Flap Valves Components: Unilaterally fixed flap Opening underneath end of flap flap Ventilklappe silicon Silizium Advantages: Compact size Low capacitance High resonance frequency Moderate dead volume Drawbacks: Low actuation force due to low effective area Klappenauflage valve plate Microfluidics - Jens Ducrée Flow Control 19

Components: Unilaterally fixed flap Opening underneath end of flap 5.1.2. Flap Valves Advantages: Compact size Low capacitance High resonance frequency Moderate dead volume Drawbacks: Low actuation force due to low effective area Microfluidics - Jens Ducrée Flow Control 20

5.1.1. Comparison: Flap / Membrane Valves Microfluidics - Jens Ducrée Flow Control 21

5.1. Check Valves 1. Membrane Valves 2. Flap Valves 3. Bivalvular Valves 4. Leakage Microfluidics - Jens Ducrée Flow Control 22

5.1.3. Bivalvular Valves Microfluidics - Jens Ducrée Flow Control 23

5.1. Check Valves 1. Membrane Valves 2. Flap Valves 3. Bivalvular Valves 4. Leakage Microfluidics - Jens Ducrée Flow Control 24

5.1.4. Leakage Leakage: Causes Assembly Internal stress Particles / contamination Possible solutions Integrated filters Combination of materials - Hard - soft Microfluidics - Jens Ducrée Flow Control 25

1. Check Valves 2. Fixed-Geometry Valves 3. Actuation Principles 4. Active Micro-Valves 5. Fluerics 5. Flow Control Microfluidics - Jens Ducrée Flow Control 26

1. Diffuser/Nozzle Valves 2. Tesla Valves 3. Hydrophobic Barriers 5.2. Fixed-Geometry Valves Microfluidics - Jens Ducrée Flow Control 27

Components: Conical channel 5.2.1. Diffuser-Nozzle Valves Advantages: Simple structure Compact size vorwärts Drawbacks: Low forward-backward ratio High leakage rate A. Olson; Valveless Diffuser Micropumps; Stockholm 1998 rückwärts Microfluidics - Jens Ducrée Flow Control 28

5.2.1. Diffuser-Nozzle Valves A. Olson; Valveless Diffuser Micropumps; Stockholm 1998 nozzle direction vorwärts diffuser direction Flow through narrow constriction Microfluidics - Jens Ducrée Flow Control 29

5.2.1. Diffuser / Nozzle Valves in Silicon Microfluidics - Jens Ducrée Flow Control 30

1. Diffuser/Nozzle Valves 2. Tesla Valves 3. Hydrophobic Barriers 5.2. Fixed-Geometry Valves Microfluidics - Jens Ducrée Flow Control 31

5.2.2. Bypass-Valves Components: Bypass with deviating angles Advantages: Simple structure Compact size forward Drawbacks: Low forward-backward ratio High leakage rate backwards Microfluidics - Jens Ducrée Flow Control 32

5.2.2. Bypass-Valves Components: Bypass with deviating angles Advantages: Simple structure Compact size vorwärts Drawbacks: Low forward-backward ratio High leakage rate rückwärts Microfluidics - Jens Ducrée Flow Control 33

1. Check Valves 2. Fixed-Geometry Valves 3. Actuation Principles 4. Active Micro-Valves 5. Fluerics 5. Flow Control Microfluidics - Jens Ducrée Flow Control 34

5.3. Actuation Principles 1. Thermal Actuators 2. Piezoelectric Actuation 3. Electrostatic Actuation 4. Electromagnetic Actuation 5. Pneumatic Actuation 6. Hydrogel Actuators 7. Bubble-Spring Actuation Microfluidics - Jens Ducrée Flow Control 35

5.3.7. Bubble-Spring Actuation Microfluidics - Jens Ducrée Flow Control 36

1. Check Valves 2. Fixed-Geometry Valves 3. Actuation Principles 4. Active Micro-Valves 5. Fluerics 5. Flow Control Microfluidics - Jens Ducrée Flow Control 37

5.4. Active Microvalves Microvalve NC 1500 Redwood Microsystems Microvalve Twente MicroProducts Microvalve MegaMic Hoerbiger-Origa

5.4. Active Microvalves 1. Definition and Concepts 2. Design Principles 3. Microvalve Actuation 4. 2-Way Microvalves 5. Microvalves for Pneumatic Systems 6. 3-Way Microvalves 7. Modeling of Flow in Microvalves Microfluidics - Jens Ducrée Flow Control 39

5.4.1. Definition and Nomenclature Valves Flow control elements Control of fluid flow in binary or continuous fashion Binary switch - Open and close position Continuous control - Continuous adjustment of flow rate between open and close closed open Anschluß 1 Anschluß 2 Anschluß 1 Anschluß 2 port 1 port 2 port 1 port 2 Microfluidics - Jens Ducrée Flow Control 40

5.4.1. Definition and Nomenclature 2- and 3-way valves Switching between different inlet and outlet ports Categorization according to number of ports Two idle modes Normally open Normally closed Microfluidics - Jens Ducrée Flow Control 41

5.4.1. Definition and Nomenclature Miniature valves: Miniaturized conventional valves Precision machining Conventional driving mechanism - Overwhelmingly electromagnetic Microvalves: Microfabrication Implementation of microactuators Miniaturized size Minimized power requirements Microfluidics - Jens Ducrée Flow Control 42

5.4.2. Construction Principles Typical design of 2-way microvalve: membrane Membran valve plate Ventilplatte Anschluß port 1 1 Anschluß port 2 2 valve Dichtkante seat Microfluidics - Jens Ducrée Flow Control 44

5.4.2. Construction Principles Equilibration of pressure for valve plate: Minimized effective area for pneumatic force pneumatic force: Membranöffnung membrane opening backside of membrane Membranrückseite Ventildeckel cover F pn p1 p2 Apn p1 p1 Fpn p1 p1 inlet (p 1 ) outlet (p 2 ) valve seat Einlaß (p1) Auslaß (p2) Dichtkante Microfluidics - Jens Ducrée Flow Control 45

5.4.2. Construction Principles Normally-open 2-way valve: membrane Membranöffnung opening membrane Membran valve Ventilplatte plate Einlaß Auslaß Auslaß Einlaß inlet outlet outlet inlet a.) equilibrated b.) non-equilibrated Microfluidics - Jens Ducrée Flow Control 46

5.4.2. Construction Principles Normally closed 2-way valves: elastic membrane Ausgleichsmembran p1 p1 Auslaß inlet p 2 p 2 Einlaß Einlaß outlet inlet Auslaß outlet a.) pretension on membrane b.) elastic valve-seat membrane Microfluidics - Jens Ducrée Flow Control 47

5.4.3. Microvalve Actuation Thermomechanical actuation: ( bimetallic membrane) T0+dT T0 r0 Material a Ftherm da db a b z Material b Feste Einspannung membrane am Rand attached to frame valve Mittenversteifung plate (movable in vertikaler in Richtung vertical direction) beweglich Microfluidics - Jens Ducrée Flow Control 49

5.4.3. Microvalve Actuation Thermomechanical actuation: ( bimetallic membrane) Maximum deflection of membrane: Maximum blocking force: (W. C. Young; Roark s Formulas for Stress & Strain; McGraw-Hill; 6. Auflage, New York, USA, 1989. ) Microfluidics - Jens Ducrée Flow Control 50

5.4.3. Microvalve Actuation Piezoelectric actuation: (piezo-bimorph) +z h U1 U2 -z Idle amplitude: Blocking force: Valvo Unternehmensbereich Bauelemente der Philips GmbH; Piezooxide (PXE) Eigenschaften und Anwendungen; Dr. Alfred Hüthig Verlag GmbH, Heidelberg, 1988 Microfluidics - Jens Ducrée Flow Control 51

5.4.3. Piezo-Electric Actuation Microfluidics - Jens Ducrée Flow Control 52

5.4.3. Microvalve Actuation Electrostatic actuation: Working principle Oppositely charged parallel plates E-field between plates One plate movable Plates attract + Isolator + + + + + + + + + + ++ ++++++++++++++++++ --------------------------------- Luft - Electrostatic force Microfluidics - Jens Ducrée Flow Control 53

5.4.3. Microvalve Actuation Electrostatic actuation: Balance of forces Snapping voltage Microfluidics - Jens Ducrée Flow Control 54

Paschen curve 5.4.3. Microvalve Actuation Microfluidics - Jens Ducrée Flow Control 55

5.4.4. Redwood Microsystems Redwood Microsystems NC-1500 Valve type: 2-way normally-closed Actuation: thermopneumatic Media: Gases Maximum pressure: 7 bar Flow rates: 0.1 ml / min 1.500 ml / min Response time: 1 s Power: 1.5 W Temperature range: 0 55 o C Tolerable particle size: 1 µm Internal volume: 0,6 ml Dimensions 6x6x2mm³ Operating voltage: 0-15 V Proportional mode possible Microfluidics - Jens Ducrée Flow Control 57

5.4.4. Redwood Microsystems www.redwoodmicro.com Pr isbexa ispel: Ausar beitun gspha Au tsarbei ungde rstand ard-ze el Flow controller Microfluidics - Jens Ducrée Druckregler Flow Control 58

5.4.4. IC-Sensors IC-Sensors (USA) Valve type: 2-way normally-closed Actuation: Thermomechanical Media: Gases Maximum pressure: 1 bar Flow rate: 0.15 l / min Response time: 50 ms Power: 0.4 W Temperature range: -20 70 o C Tolerable particle size: 25 µm Operating voltage: 5 V Gas flow (sccm) 400 mw 300 mw 200 mw Input pressure (PSI) Microfluidics - Jens Ducrée Flow Control 59

5.4.4. Lawrence Livermore National Laboratory Lawrence Livermore National Laboratory: Valve type: 2-way normally-open Actuation: electrostatic with 1-µm polyimide cantilever Valve amplitude:200 µm Media: Gases Maximum pressure: 0.2 bar Flow rate:? Response time:? Power: 10 µw Temperature range:? Size? Microfluidics - Jens Ducrée Flow Control 60

5.4.4. Twente Microproducts Twente Microproducts: Valve type: 2-way Bistable (NO / NC) Rubber-membrane Actuation: electromagnetic Combination of permanent magnet and electromagnet Microfluidics - Jens Ducrée Flow Control 61

5.4.4. Electromagnetic Actuation Microfluidics - Jens Ducrée Flow Control 62

5.4.4. Twente Microproducts Twente Microproducts: Media: Gases, Liquids Maximum pressure: 2 bar Gap diameter: 0.2 mm Response time:? Operating current: 0.5 A Power: no blocking power Dead volume: < 5 µl Dimensions: 6 x 6 x 6 mm³ Microfluidics - Jens Ducrée Flow Control 63

5.4.4. Industrial Microelectronics Center (IMC) IMC (Sweden): Valve type: 2-way normally-open Actuation: Pneumatic Silicone membrane Comparison of deflections of 0.2 x 0.2 mm membrane made of different materials. (Thickness adapted for maximum pressure head of 5 bars) Microfluidics - Jens Ducrée Flow Control 64

5.4.4. Industrial Microelectronics Center (IMC) IMC (Sweden): Valve type: 2-way normally-open Actuation: pneumatic Media: Gases or liquids Actuation pressure depends on hydrodynamic pressure of flow to be switched Microfluidics - Jens Ducrée Flow Control 65

5.4.5. Miniature Valves State of the Art Trends in Automation Technology: Intelligent, decentralized subsystems Communicating over common data bus Miniaturization Integration of electronics Present Situation: Reduction of electric power consumption electromagnetic and piezoelectric actuation Typical power consumption 0.5 1 W Various miniaturized valves already feature power consumption below 10 mw which can be controlled by bus system Microfluidics - Jens Ducrée Flow Control 67

5.4.5. Miniature Valves State of the Art Electromagnetically actuated miniature valve: Manufacturer: SMC Type: 3-way, normally-closed Pressure range: 0 7 bar Flow rate:8 l / min Media: Temperature range: < 50 C Power: 500 mw Response time: < 10 ms Width of housing: 10 mm filtered, compressed air Quelle: Fa. SMC Microfluidics - Jens Ducrée Flow Control 68

5.4.5. Miniature Valves State of the Art Electromagnetically actuated miniature valve: Manufacturer: Bürkert Type: 3-way, normally closed Pressure range: 0 10 bar Flow: 4 l / min Media: dry, filtered air Temperature range: -25 C - 80 C Power: 10 mw Response time: 20 ms Source: Fa. Bürkert Microfluidics - Jens Ducrée Flow Control 69

5.4.5. Miniature Valves State of the Art Piezoelectrically actuated miniature valve: Manufacturer: Hoerbiger-Origa Type: 3-way, normally closed Pressure range: 0 2 bar Flow: 1.5 l / min Media: dry, filtered compressed air Temperature range: -10 C - 60 C Power: 6 mw Response time: 2 ms Housing: 19 mm Source: Hoerbiger-Origa Microfluidics - Jens Ducrée Flow Control 70

5.4. Active Microvalves 1. Definition and Concepts 2. Design Principles 3. Microvalve Actuation 4. 2-Way Microvalves 5. Microvalves for Pneumatic Systems 6. 3-Way Microvalves 7. Modelling of Flow in Microvalves Microfluidics - Jens Ducrée Flow Control 71

5.4.6. MegaMic Valve Series of HSG-IMIT Normally-open, electrostatically actuated 2-way valve valve plate chip Ventilplattenchip elastische Aufhängung elastic support opening Zuluftöffnung valve plate Ventilplatte valve gap Ventilspalt outlet Auslaßöffnung outlet chip Auslaßchip valve Ventilsitz seat Isolationsschicht insulation layer Microfluidics - Jens Ducrée Flow Control 72

5.4.6. Microvalves for Gases System concept 3-way valve (switch) Electrostatic actuation Normally-closed by mechanical pretension Gehäuse housing pressure port ceramics Keramik Auslass port pressure Druckanschluss port Entlüftung outlet port outlet Microfluidics - Jens Ducrée Flow Control 73

5.4.6. Microvalves for Gases System concept 3-way valve (switch) Electrostatic actuation Normally-closed by mechanical pretension U housing Gehäuse pressure port ceramics Keramik Druckanschluss Auslass port pressure port Entlüftung outlet port outlet Microfluidics - Jens Ducrée Flow Control 74

5.4.6 Microvalves Characteristics: Housing: Response time: Power: Pressure range: Max. flow: 7 x 10 x 16 mm³ < 1 ms 3 mw 10 bar (16 bar) 1 l / min Pneumatics (10 bar) Microfluidics - Jens Ducrée Flow Control 75

5.4.6 MegaMic-Valve Series of HSG-IMIT manufacturing of outlet wafer a e b f c g d 54,7 h Microfluidics - Jens Ducrée Flow Control 76

5.4.6 MegaMic-Valve Series of HSG-IMIT manufacturing process of valve plate chip a e b f c g d h Microfluidics - Jens Ducrée Flow Control 77

5.4.6 MegaMic-Valve Series of HSG-IMIT manufacturing of cover chip a Si e SiO2 Si b f c g d Microfluidics - Jens Ducrée Flow Control 78

5.4.6 MegaMic-Valve Series of HSG-IMIT full-wafer bonding and dicing of valve chip b a c Microfluidics - Jens Ducrée Flow Control 79

5.4.6 MegaMic-Valve Series of HSG-IMIT packaging and assembly cap contacts steel ball valve chip gasket metallization carrier (ceramics) gasket (flat) Microfluidics - Jens Ducrée Flow Control 80

5.4.6 MegaMic-Valve Series of HSG-IMIT Electrostatically actuated 3-way microvalve MegaMic Characteristics: -Pressure range: 10 bar -Flow rate: typ. 0.5 l / min -Response time: < 1 ms -Power: 3 mw -Temperature range: -40 C 80 C Microfluidics - Jens Ducrée Flow Control 81

5.4.6 MegaMic-Valve Series of HSG-IMIT Measurement of volume flow from pressure to working port Volume discharge 12 dv /dt [ml/min] 600 500 400 300 200 100 p 2 = 0 bar p 3 = 0 bar U e = 200 V Measurement valve 1_2 valve 2_2 valve 3_2 valve 4_2 pressure Druckanschluß 0 0 1 2 3 4 5 6 7 8 Pressure at pressure port p 1 [bar] working port Arbeitsanschluß outlet Entlüftung Microfluidics - Jens Ducrée Flow Control 82

5.4.6 MegaMic-Valve Series of HSG-IMIT Measurement of volume flow from pressure to outlet Volume discharge dv 23 /dt [ml/min] 600 500 400 300 200 100 p 1 = p 2 p 3 = 0 bar U e = 0 V 0 0 1 2 3 4 5 6 7 8 Pressure at working port p 2 [bar] Measurement valve 1_2 valve 2_2 valve 3_2 valve 4_2 pressure Druckanschluß working port Arbeitsanschluß outlet Entlüftung Microfluidics - Jens Ducrée Flow Control 83

5.4.6 MegaMic-Valve Series of HSG-IMIT Measurement of electric switching characteristics Volume discharge dv 12 /dt [ml/min] 500 400 300 200 100 U p s,2 U 1 = 6 bar s,1 p 2 = 0 bar p 3 = 0 bar 0-20 0 20 40 60 80 100 120 140 160 180 200 220 Voltage U e [V] Measurement valve 1_2 pressure Druckanschluß working port Arbeitsanschluß outlet Entlüftung Microfluidics - Jens Ducrée Flow Control 84

5.4.6. Applications for MegaMic Kooperation mit HOERBIGER-ORIGA Microfluidics - Jens Ducrée Flow Control 85

5.4.6. FhG-Institut für Siliziumtechnologie Valve type: 3-way normally-open Pressure distribution principle Nozzle / collision plate Actuation: thermomechanical Gap opening: 60 µm Media: Maximum pressure: Flow rate: Response time: Power: Gases 9 bar 1.5 l / min 35 ms 600 mw Temperature range:? Dimensions 6x6x2 mm³ Microfluidics - Jens Ducrée Flow Control 86

5.4.6. FhG-Institut für Siliziumtechnologie Valve type: 3-way normally-open Pressure distribution principle Nozzle / collision plate pressure Druckanschluß Arbeitsanschluß working port Entlüftung = outlet Drossel Microfluidics - Jens Ducrée Flow Control 87

5.4. Active Microvalves 1. Definition and Concepts 2. Design Principles 3. Microvalve Actuation 4. 2-Way Microvalves 5. Microvalves for Pneumatic Systems 6. 3-Way Microvalves 7. Modelling of Flow in Microvalves Microfluidics - Jens Ducrée Flow Control 88

1. Check Valves 2. Fixed-Geometry Valves 3. Actuation Principles 4. Active Micro-Valves 5. Fluerics 5. Flow Control Microfluidics - Jens Ducrée Flow Control 89

5.5. Flow Switches 1. Hydrodynamic Flow Switches 2. Microfluidic Flip-Flop 3. Hydrodynamic Oscillator 4. Microfluidic Proportional Amplifier Microfluidics - Jens Ducrée Flow Control 90

5.5.1. Hydrodynamic Flow Switch Microfluidics - Jens Ducrée Flow Control 91

5.5.2. Microfluidic Flip-Flop Microfluidics - Jens Ducrée Flow Control 92

5.5.3. Microfluidic Oscillator Microfluidics - Jens Ducrée Flow Control 93

5.5.4. Microfluidic Proportional Amplifier Microfluidics - Jens Ducrée Flow Control 94