Microfluidics and Lab-on-a-chip systems. Pelle Ohlsson

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1 Microfluidics and Lab-on-a-chip systems Pelle Ohlsson

2 Today Who am I? What is microfluidics? What is the concept Lab-on-a-chip systems? What happens when you scale things down? Some applications of this

3 What is microfluidics?

4 What is a fluid?

5 What is micro?

6 What is micro? mc3cb.com, islandweavings.blogspot.se, en.wikipedia.org/wiki/blood

7 What is micro? reverseosmosis.co.uk, redorbit.com, webbofscience.com,

8 Miniaturization + Faster + Cheaper + Portable + Less manual work + Less consumption (power) Pictures:

9 Miniaturization Lab-on-a-chip: + Faster + Cheaper + Portable + Less manual work + Less consumption (sample, chemicals) + New things possible Pictures:

10 Miniaturization Lab-on-a-chip: Capillary electrophoresis (CE) + Faster + Cheaper + Portable + Less manual work Microchip electrophoresis (MCE) + Less consumption (sample, chemicals) + New things possible Pictures:

11 Microfluidics around us? companionplants.com

12 What happens when you scale things down?

13 Fluid mechanics at the microscale L Surface-to-volume ratio: SSSSSSS VVVVVV L2 L 3 = 1 L Surface effects Mass Momentum Adhesion Volume effects Kinetic energy Viscosity

14 Reynolds number viscosity hydraulic diameter e.g. dimension, typical velocity typical density Re cos 2 2 = = = = = + = + η ρ η ρ η ρ ρ L u L u x u x p x u u t u ity vis j j i effects inertial i j i i i F

15 Reynolds number High Reynolds number (~ >2500) turbulent flow

Reynolds number Low Reynolds number (~ <1500) laminar/creeping/stokes flow Re 10-11 Weibel et al.

16 Reynolds number Low Reynolds number (~ <1500) laminar/creeping/stokes flow Re Weibel et al. Analytical Chemistry, Vol. 77, No. 15, August 1, 2005 ChemPhysChem 2008, 9, ,

17 Reynolds number Low Reynolds number (~ <1500) laminar/creeping/stokes flow Vortices may still form in the cavities!

18 Video: Laminar flow

19 Pressure driven flow in circular channels r Q = V t = 4 πr0 8η L p

20 Mixing

21 Laminar flow and diffusion d = 222 M. Evander & M. Tenje (2013)

22 Lamination

23 Chaotic micromixer G.M. Whitesides et al Science Vol Jan

24 Chaotic micromixer G.M. Whitesides et al Science Vol Jan

25 Chaotic micromixer Straight channel Herring bone Slanted grooves G.M. Whitesides et al Science Vol Jan

26 How can you move liquids?

27 Syringe pumps

28 Peristaltic pumps cnzhidan.en.made-in-china.com reefbuilders.com

29 Capillary forces

30 Paper microfluidics

31 4castchip 0:30

32 Pressure driven flow

33 Gravitaty springer.com

34 Centrifugal forces

35 Electrowetting

36 Electrowetting Abdelgawad et al. Lab Chip, 2008, 8,

37 Droplets Two phase systems 0:30

38 Electroosmosis O - H + OH O - H + Si Si Si Deprotonation of silanol groups Glass

39 Electroosmosis Electroosmotic mobility: µ eo = v eo E Can be modified by: Bulk electrolyte - ph - coating - voltage applied to substrate Diffuse layer Fixed layer Channel wall

40 Electroosmotic flow Pressure driven flow p 0 +Δp p 0

41 Electrophoresis v ep v eo v ep v eo v tot v tot v eo N v tot - Separation depending on the ratio between charge and viscous drag

42 Chemical separations

43 Spiral chips: cm separation channels 24 mm 17 mm

44 Spiral chips: cm separation channels Filters 24 mm 17 mm

45 Electrokinetic valving gated injection 24 mm 17 mm

46 NeuroTAS June 2008 Spiral chips: cm separation channels 24 mm Separation channel 17 mm 46 / 36

47 Spiral chips: cm separation channels 10 μm 20 μm 24 mm Separation channel 30 μm 40 μm 17 mm

48 Spiral chips: cm separation channels 24 mm Detection cell 17 mm

49 Absorbance detection A = εvs Problem: short pathlength Solution: detection in plane

50 Visual absorbance detection Pregnancy test

51 Visual absorbance detection Allergy test

52 Fluorescence detection Epifluorescence detection Laser Detector Detection at an angle

53 Fluorescence detection Confocal fluorescence detection

54 Fluorescence detection Confocal fluorescence detection Even single molecules can be detected! Single DNA molecule (6 pm) stained with YOYO-1

55 Fluorescence detection Increased interaction length using waveguides

56 Fluorescence detection Integration of dye laser and photo diodes S. Balslev et al. Lab. Chip., 2006, 1,

57 Counting cells

58 Why count cells?

59 Flow cytometry Counting beads RBCs Platelets E coli

60 Imaging cytometers

61 Flow cytometry Lab Chip, 2012, 12,

62 Fluorescence activated cell sorting (FACS)

63 Electrical cell counting

64 Cell counting and sizing Coulter counter A

65 Impedance spectroscopy Impedance measurement from khz to MHz E.g. counting and identification of cells Holmes, D. et al, IEEE Sensors 2007,

66 Impedance spectroscopy Impedance measurement from khz to MHz E.g. counting and identification of cells Holmes, D. et al, IEEE Sensors 2007, Holmes, D. et al, IEEE Sensors 2007,

67 Sorting cells using sound

68 Kundt s tube in a microchannel?

69 Kundt s tube in a microchannel? Piezoelectric transducer w = n λ 2 Laurell et al, Chem Soc Rev (2007) wikipedia.org

70 Effect of contrast factor φ = 1 k 3 ρ 1 + 2ρ + 1 Positive => node Negative => anti-node k ρ = relative compressibility = relative density of particle with respect to fluid

71 Blood from heart surgery H. Jönsson et al, SocThorSurg (2004)

72 Blood from heart surgery

73 Sepsis

74 Primary axial acoustic radiation force F r = 4πr 3 E aa k sss 222 φ β, ρ r F r f F r Contrast factor φ = 1 k 3 ρ 1 + 2ρ + 1 F r = acoustic radiation force E ac = acoustic energy density r = particle radius k = wave number (2π/λ) x = particle distance to the node k ρ = relative compressibility = relative density of particle with respect to fluid

75 Separating bacteria from blood

76 Inlet Outlet

77 Acoustic trapping Flow Transducer

78 Separation, enrichment and PCR of bacteria from blood

79 Separation, enrichment and PCR of bacteria from blood

80 Reading DNA and RNA

81 Why read DNA and RNA?

83 PCR chip

84 Continous flow PCR Y. Zhang, P. Ozdemir / Analytica Chimica Acta 638 (2009)

85 DNA in nanochannels The persistence length (P) of dsdna is typically ~50 nm. DNA confinement in nanochannels: physics and biological applications, Walter Reisner, Jonas N Pedersen and Robert H Austin, Reports on Progress in Physics, Volume 75 Issue 10, 2012

86 DNA in nanochannels DNA confinement in nanochannels: physics and biological applications, Walter Reisner, Jonas N Pedersen and Robert H Austin, Reports on Progress in Physics, Volume 75 Issue 10, 2012

Length of DNA E. coli: a) 1.6 µm b) 1.6 mm c) 1.6 m http://english.globalgujaratnews.

87 Length of DNA E. coli: a) 1.6 µm b) 1.6 mm c) 1.6 m DNA confinement in nanochannels: physics and biological applications, Walter Reisner, Jonas N Pedersen and Robert H Austin, Reports on Progress in Physics, Volume 75 Issue 10, 2012

Length of DNA The human (diploid) genome: a) 2 cm b) 2 dm c) 2 m http://globalgenes.

88 Length of DNA The human (diploid) genome: a) 2 cm b) 2 dm c) 2 m DNA confinement in nanochannels: physics and biological applications, Walter Reisner, Jonas N Pedersen and Robert H Austin, Reports on Progress in Physics, Volume 75 Issue 10, 2012

89 Nanopores Nature Biotechnology 26, (2008)

90 Organs on chip Improved In-vitro models, eg. for drug testing

91 How do you make microfluidic chips?

92 Cleanroom

93 Photolitography 1. Spin on photoresist 2. UV lithography 3. Develop photoresist 4. Bond glass lid Silicon (Si) Photoresist Borofloat glass

94 Silicone molding 1. Pour on PDMS 2. Cure 3. Peel off 4. Bond glass or PDMS lid Silicon (Si) Photoresist Borofloat glass PDMS silicone

95 Etching 1. Etch 2. Remove photoresist 3. Bond glass lid Silicon (Si) Photoresist Borofloat glass

96 Micromilling

97 3D-printing

98 3D laser photopolymerization

99 Summary Surface effects dominate over volume effects Laminar flow Miniaturization of existing methods New phenomena

100 Mer mikrofluidik: Introduktion till mikrofluidik och lab-on-a-chip-system (LP1) Lab-on-a-chip i biomedicinska tillämpningar (LP4) Exjobb bme.lth.se

101 Questions

Lecture 18: Microfluidic MEMS, Applications

MECH 466 Microelectromechanical Systems University of Victoria Dept. of Mechanical Engineering Lecture 18: Microfluidic MEMS, Applications 1 Overview Microfluidic Electrokinetic Flow Basic Microfluidic