Microfluidic Principles Part 1

Transcription

1 Introduction to BioMEMS & Medical Microdevices Microfluidic Principles Part 1 Companion lecture to the textbook: Fundamentals of BioMEMS and Medical Microdevices, by Dr. Steven S. Saliterman

2 Microfluidic Devices Microtiter Plate Micromixer Various Devices Microelectrodes Images Courtesy of Micronit

3 Microfluidic Device Market Yole Development, 2011

4 Example: LOC for DNA Hybridization Analysis Hadar Ben -Yoav et al, A controlled microfluidic electrochemical lab-on-a-chip for label-free diffusion-restricted DNA hybridization analysis, Biosensors and Bioelectronics 64(2015) , 2014.

5 LOC for DNA Hybridization Analysis Hadar Ben -Yoav et al, A controlled microfluidic electrochemical lab-on-a-chip for label-free diffusion-restricted DNA hybridization analysis, Biosensors and Bioelectronics 64(2015) , 2014.

6 Transport Process Considerations Required sample size. Characteristics of fluids. Reynolds Number and Laminar flow. Surface area to volume. Diffusion Electrokinetic phenomena. Other driving forces.

7 Typical Device Components Microducts Micronozzles Micropumps Microturbines Microvalves Microsensors Microfilters Microneedles Micromixers Microreactors Microdispensers Microseparators

8 Dimensional Considerations Nguyen, NT and ST Wereley, Fundamentals and Applications of Microfluidics, Artech House, Boston, MA (2002).

9 Analyte Concentrations in Serum DNA Electrolytes Peterson, KE et al., Toward next generation clinical diagnosis instruments: scaling and new processing paradigms. Journal of Biomedical Microdevices 2(1), pp (1999).

10 Determining Sample Volume The relationship between sample volume (V) and analyte concentration is shown here: 1 V =, hsna Ai where h (eta) is the sensor efficiency 0 h 1, s N A i A 23 is , or Avogadro s number, and is the concentration of analyte, i. The higher the concentration of analyte and/or better the sensor, the less the volume of sample that is needed. s

11 Example: K + (Potassium) in Serum Potassium has a concentration of 3.5 to 5.3 mmol/liter in serum. Assume a sensor efficiency of 0.1, and concentration of 3.5 mmol/liter, approximately what is the smallest volume needed:

12 Sample Requirements for Detection Previous example: K + Given Concentration Peterson, KE et al., Toward next generation clinical diagnosis instruments: scaling and new processing paradigms. Journal of Biomedical Microdevices 2(1), pp (1999).

13 What is a Fluid? A fluid is a substance that deforms continuously under the application of shear (tangential) stress of any magnitude. This includes gases and liquids. Newtonian Solid - Returns Fluid Remains Deformed Adopted from Nguyen, NT and ST Wereley, Fundamentals and Applications of Microfluidics, Artech House, Boston, MA (2002).

14 Terminology: Viscosity t=m du dy, where t (tau) is the shearing stress, m (mu) is the absolute or dynamic viscosity, and du is the velocity gradient. dy Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

15 Kinematic Viscosity Kinematic viscosity of a fluid relates the absolute viscosity to density: where m n= r, n (nu) is the kinematic velocity (m /s), m (mu) is the absolute viscosity, and r (rho) is the density or mass per unit volume; 2

16 Specific Weight & Specific Gravity The specific weight of a fluid is defined as the weight per unit volume: g=rg, where g (gamma) is specific weight, r (rho) is the density or mass per unit volume, g is the local acceleration due to gravity; The specific gravity (SG) of a fluid is the ratio of the density of the fluid to the density of water at some specified temperature: SG = r r HO C

17 Flow Continuum assumption. Laminar vs. transitional and turbulent flow. Reynolds number. Fluid kinematics. Field representation Hagen-Poiseuille flow, pronounced pwäz-'wē. Poiseuille s law. Surface area to volume. Diffusion

18 Factors Influencing Flow Kinematic properties - velocity, viscosity, acceleration, vorticity. Transport properties - viscosity, thermal conductivity, diffusivity. Thermodynamic properties - pressure, thermal conductivity, density. Other properties - surface tension, vapor pressure, surface accommodation coefficients.

19 Reynolds Number In circular tube flows without obstruction, conventional fluid mechanics would dictate that Reynolds numbers smaller than about 2100 typically indicate laminar flow, while values greater than 4000 are turbulent. In between is transitional. Ratio between inertial and viscous forces: rvd Re =, m where r (rho) is the fluid density, V is the mean fluid velocity, D is the pipe diameter and m (mu) is the fluid viscosity. Osborne Reynolds lived from 1842 to 1912 and was an Irish fluid dynamics engineer.

20 Example: Reynolds Number In a channel carrying water (viscosity of 10-3 kg/(s m), density of 10 3 kg/m 3 ), in a channel with diameter of 10 µm, at a velocity of 1 mm/s, the Reynolds number is 10-2 :

21 Contrast this to a channel with diameter of 100 µm and fluid velocity of 10 m/s, where the Reynolds number is a 1000:

22 Microfluidic Flow Challenges Flows at low Reynolds numbers pose a challenge for mixing. Two or more streams flowing in contact with each other will mix only by diffusion. As surface area to volume increases surface tension forces become significant, leading to nonlinear free-boundary problems. As suspended particle sizes approach the size of the channel, there is a breakdown of the traditional constitutive equations.

23 Fluid Kinematics A field representation of flow is the representation of fluid parameters as functions of spacial coordinates and time. The velocity field is defined as: V= uxyzt (,,,) ˆi+ vxyzt (,,,) ˆj+ wxyzt (,,,), kˆ where u, v, w are the x, y, and z components of the velocity vector, and t is time. For problems related to flow in most microchannels, we can consider that one or two of the velocity components will be small relative to the others, and reduce the problem to 1D or 2D flow.

24 Position Vector Particle location is in terms of its position vector r A : Adopted from Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

25 The velocity of a particle is the time rate of change of the position vector for that particle: dr A / dt= V A The direction of the fluid velocity relative to the x axis is given by: tan q= v u Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

26 Streamlines A streamline is a line that is everywhere tangent to the velocity field. In steady flows, the streamline is the same as the pathline, the line traced out by a given particle as it flows from one point to another. tan q= v u For a 2D flow the slope of the streamline must be equal to the tangent of the angle that the velocity vector makes with the x axis: dy dx = v u Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

27 If the velocity field is known as a function of x and y, this equation can be integrated to the give the equation of the streamlines. The notation for a streamline is: y (psi) = constant on a streamline The stream function is: y=y( x, y) Various lines can be plotted in the x-y plane for different values of the constant. For steady flow, the resulting streamlines are lines parallel to the velocity field. Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

28 Uniform Flow The streamlines are all straight and parallel, and the magnitude of the velocity is constant. Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

29 Streamline Coordinates V= Vsˆ Velocity is always tangent to the s direction. Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

30 Flow Around a Circular Cylinder Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

31 Flow Net ( xyzt,,, ) u v w (phi) x y z (psi) Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

32 Acceleration Where n 2 2 V V V V a V sˆ nˆ or as V, an s s is the local radius of curvature of the streamline, as is the convective acceleration along the streamline, and a is the centrifugal acceleration normal to the fluid motion.

33 Hagen-Poiseuille Flow Hagen-Poiseuille flow or Poiseuille flow is the steady, incompressible, laminar flow through a circular tube of constant cross section. The velocity distribution is expressed as : æ pö æ 2 2 ö, ç z çè ø çè ø v 1 z = r -R 4m where m (mu) is the fluid viscosity, p/ z is the z component of the pressure gradient, r is the distance from the center of the tube, and R is the radius of the tube. Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

34 Velocity Distribution The velocity distribution is parabolic at any cross sectional view: Adopted from Young, DF, et al, A Brief Introduction to Fluid Mechanics, 2 nd ed., Wiley, New York (2001).

35 Poiseuille s Law Poiseuille s law describes the relationship between the volume rate of flow, Q, passing through the tube and the pressure gradient: where 4 4 Q= pd Dp = pr Dp, 128m 8m Q is the volume rate of flow, D is the diameter of the tube, Dp is pressure drop over length, along the tube, m (mu) is the fluid viscosity, and R is the radius of the tube.

36 The mean velocity is: V 2 Q R Dp = = pr 2 8 m and the maximum velocity occurring at the center of the tube is: v = 2 V. max

37 Surface Area to Volume Surface area to volume (SAV) increases significantly as dimensions are reduced for microfluidic channels. For example, for a circular microchannel 100 µm in diameter, the SAV ratio is: 2prL SAV = = = 4 10 m, 2 prl r where r is the radius, and L is the length.

38 Diffusion In laminar flow, two or more streams flowing in contact with each other mix only by diffusion. x 2 RT ln y = 2 Dt, D= 1 + C, 6ph r N ê ç C ú where x is the distance a particle moves, t is the amount of time, and D is the diffusion coefficient. where A A ê çè ø ë TP, ú û R is the gas constant, T is temperature, r is particle radius, N is Avogadro s number, é C is concentration in moles/liter, h (eta) is the solution viscosity, and y is the activity coefficient in moles/liter. æ ö ù

39 Example: Diffusion of Hemoglobin How long does it take hemoglobin to diffuse 1 cm in water (D=10-7 cm 2 s -1 )? (58 days!) How long to diffuse 10 µm (.001 cm)?

40 Design Considerations The optimal size domain for microfluidic channel cross sections is somewhere between 10 µm and 100 µm. At smaller dimensions detection is too difficult and at greater dimensions unaided mixing is too slow. Therefore, the typical cross section diameter will be ~2 x 10-3 mm 2. The flow range will be 1 to 20 nl/sec. When diluting an assay component, the two flows must be controlled within ~1%, or pl/sec range.

41 Technique: Continuous Flow Assay Sample material is injected into a stream as a plug, with interspaced amounts of buffer solution. Pressure-driven flow is commonly used to transport the plugs through a network of interconnecting channels where reagents may be added and mixed, allowing reactions to occur. Sample Buffer Beebe DJ et al, Annual Reviews of Biomedical Engineering 2002, 4:261-86

42 Summary Microfluidic devices and growing market. Typical device components. Transport process considerations. Dimensional considerations. Volumes required for detection of analytes. Fluid dynamics based on the continuum assumption. Surface area to volume. Diffusion Technique: Continuous flow assay.