1. Microfluidics and BioMEMS Introduction 13.1.2016 Sami Franssila & Ville Jokinen

2. Many keywords Microfluidics Bio-MicroElectroMechanical Systems Lab-on-a-chip Can be used interchangably, Even though not exactly synonyms

3. Multidisciplinary science 1.Fundamental science relating to micro and nanoscale fluids (physics, chemistry) 2.Fabrication of microfluidic devices (engineering, materials science, etc.) 3.Applications (a plethora of fields, engineering, chemistry, biology) On this course we will focus on: Fundamental aspects of microfluidics and microfabrication Common features and advantages of microsystems Selected application fields (analytical chemistry, biochemistry, cells/tissue on chip) Microfluidics can mean many things:

4. Start of an era: Gas chromatograph on silicon (1979): -injector -separation channel -thermal conductivity detector Gas fluidics minor activity compared to liquid fluidics (which started in 1990)

5. Is microfluidics different ? 1. Laminar flow 2. Small size scales 3. Scaling effects 4. Parallelization and integration Some important features of microfluidics:

6. Why miniaturize ? because it is possible? because it is improves performance? because it opens up new possibilities? "Courtesy Sandia National Laboratories, SUMMiT TM Technologies, www.mems.sandia.gov"

7. 1. Laminar flow A key difference between micro and macrofluidics: laminar flow Laminar flow means no turbulence. The streamlines are stable over time. Laminar flow physics is easy (while turbulence is still somewhat unsolved) Laminar flow is predictable, can be modeled and enables many applications.

8. Turbulent vs. laminar flow Turbulent = efficient mixingLaminar: slow mixing by diffusion

9. Laminar flow application: odour sensing Different odour-containing fluids are directed past the nose of a worm C.Elegans, which is kept stationary in one channel. Worm reactions to odours are detected (by fluorescent calcium receptor signal). Buffer removes odour, and switching to a different channel, a new odour is brought to worm.

10. Microfabrication Nanofabrication 2. Small size scales Many opportunities by fabricating structures at roughly the same scale as analytes.

11. Typical sizes in microfluidics Microfluidic channels: width and height 10 – 100 µm, length 1 mm – 1 cm Pores and gaps, > 10 nm Volumes: a microfluidic chip 1 µl, ink jet droplets 1-10 pl Size of a microfluidic chip, 5mm – 5 cm.

12. Micropumped systems Volume flow rates (Q) of micropumps are in the range of 1 nl/min to 1 ml/min (1 nl = 10 -9 l = 10 -12 m 3 ) Volume flow rate Q = A *v [m 3 /s = m 2 *m/s] Linear flow rate v= Q/A Q = 1 nl/min = 10 -12 m 3 /60 s = 16.7*10 -15 m 3 /s If channel cross section is 100 µm*100 µm (10 -4 m) v = 16.7*10 -15 m 3 /s /(10 -4 *10 -4 m 2 )=1.67*10 -6 m/s ≈ 2 µm/s Q= 1 µl/min  2 mm/s

13. 3. Scaling effects Volume scales as d 3 Surface area scales as d 2 → Body forces to surface forces scale as d. → Micro and nanoscale is dominated by surface effects. Example: A small glass capillary will fill spontaneously by capillary action (surface force) even against gravity (body/volume force) while a garden hose will not. Diffusion time scales as d 2 → Micro and nanoscale diffusion is fast and can even be used for mixing. Amount of analyte scales as d 3 → Amount of analyte can be low, detection methods need to be sensitive.

14. Scaling: diffusion & detection Cube edge1 mm100 µm 10 µm1 µm Cube volume1 µL1 nL 1 pL1 fL Diffusion time (small protein) ≈ 3 hours 100 s 1 s10 ms #molecules (1 µM) 6*10 11 6*10 8 6*10 5 600

15. 4. Parallelization and integration Microfluidic devices lend themselves well to parallelization due to the small size and the parallel nature of many microfabrication processes. Lab-on-a-chip concept: everything necessary for the application is provided on chip. (also called µTAS, micro total analysis system) Often in practice, lots of off chip equipment and connections used.

16. Protein interaction chip Radiolabeling synthesis reactor for PET S. Quake 256-mixer Large scale fluidic integration

17. Fluidic connectors Ville Saarela, TKK

18. Chemical microfluidics -separation systems (CE, LC, GC,...) -detectors (microelectrodes, MS, photodiodes,...) -droplet generators (ESI) -ionization systems (corona, UV,...) -synthesis reactors -gradient generators -crystallization chips -...

19. APCI-MS, Atmospheric Pressure Chemical Ionization Mass Spectrometry

20. Drug delivery 100 identical drug chambers Drug release by electrical puncturing of a gold membrane

21. Physical microfluidics cooling ICs and high power lasers power-MEMS: combustion engines, fuel atomizers, fuel cells fluidic optical switching fluid sensors (rate, viscosity, shear,...) MAVs = Micro Air Vehicles microrockets fluidic logic

22. Electronic paper by electrowetting

23. BioMEMS Microdevices for handling biomolecules, cells, bacteria, viruses, tissue, model-organs All BioMEMS devices are microfluidic devices, because biology takes place in water Bio-MEMS Devices to Monitor Neural Electrical Circuitry Andres Huertas, Michele Panico, Shuming Zhang

24. Sperm selection

25. Lung model (organ-on-a-chip) Chip for mimicking lungs. 2 types of cells cultured on opposite sides of a stretchable membrane. Stretching simulates breathing-induced mechanical movements. Ingber et al. Wyss Institute

26. Microfluidic benefits Many functions can be integrated in a single device Small volumes lead to fast reactions Sensitivity is enhanced because of high surface-to-volume ratios Laminar flow easy to control