Introduction to Microfluidics By LNF Microfluidics ...

1 LNF Microfluidics workshop 2014 Introduction to Microfluidics By Pilar Herrera-Fierro 3/10/ 2014 LNF microfluidic workshop 2014 Intro to BioMEMS Surface properties and modifications Soft Lithography Making the mold: SU-8 or Si metal deposition Basic Microfluidics design considerations 3/10/ 2014 LNF microfluidic workshop 2014 EECS 509 BioMEMS What Are MEMS Microsystems? Micro Electro Mechanical Systems Are Miniature, Multifunctional Microsystems Consisting of Sensors, Actuators, and Electronics. They Are Built Using Micromachining Technologies. Micromachining Is an Enabling Technology That Allows Formation Of Physical, As Well As Electronic, Devices. Micromachining Uses Many of the Standard Silicon IC Fabrication Techniques. EECS 509 BioMEMS Surface-Micromachined Acceleration Sensor (Accelerometer) For Air Bag Deployment, Manufactured by Analog Devices, Inc.

2 Photos Courtesy Analog Devices, Inc. ~1-2mm ADXL05: 5g operating range 1000g survivability Hz noise floor Only a few $! Undercut polysilicon shuttle mass Differential capacitance sensing Force-balanced operation EECS 509 BioMEMS BioMEMS Implementation of MEMS (Micro Electro Mechanical Systems) to Bio-related areas Fluid delivery system at micro/nano-liter scale Multi-physics, multidisciplinary and cross-fields BioMEMS, Lab-on-a-chip EECS 509 BioMEMS BioMEMS Biomedical MEMS Biosensors Biotelemetry Drug delivery Precision surgery Minimally-invasive therapy Physical sensors Deals in vivo with the host anatomy Biotechnological MEMS Gene sequencing Functional genomics Drug discovery Pharmacogenomics Diagnostics Pathogen detection Deals in vitro with the biological samples of the host Future BioMEMS.

3 Combination of MEMS for in vitro Diagnostics with in vivo Therapy - Biology Perspective - EECS 509 BioMEMS Applications of BioMEMS Advancement in molecular biology Have brought medical research into molecular level Advancement in nanotechnology Manipulation of scale in molecular size possible The applications -Biological analysis -Medical diagnosis -Antigen/Antibody screening -Chemical analysis and synthesis -Drug discovery -Drug screening - EECS 509 BioMEMS Biomedical Applications of MEMS Implantable Systems Functional muscular stimulation (restore limb movement) Auditory, and Visual Prostheses Overcome disabilities such as Parkinson and Epilepsy Pain control, Bladder control, Drug Delivery Systems, Biological Fluid Analysis Systems DNA Analysis Blood Testing/Typing Chemical/Biological Analysis Cell-Based Assay Chips Patient Health Monitoring Measure Patient Health Signs (Activity, breathing, chemistry.)

4 Patient Health Service (drug delivery, ..) Environmental Sensing Air quality Water quality, and drug dosing - MEMS & Microsystem Perspective - EECS 509 BioMEMS Courtesy of Prof. Carlos Mastrangelo THERMAL REACTION DROP METERING SAMPLE LOADING GEL LOADING SEPARATE DETECT Integrated DNA Analysis Multiple components Multiple reactions/separations Decrease size/volume EECS 509 BioMEMS Single-Cell Assay Microsystem Flow direction Capture site Captured cell Actuation membrane Concentration Generator Microchamber Selection Logic Peristaltic Pump High-throughput Parallel Cell Assay at Single Cell Resolution -Optimal stem cell culture & transplantation -Cancer drug screening microfluidic Logic Network Microchamber Array for Single-Cells Prof. E. Yoon, University of Michigan EECS 509 BioMEMS Neuro Implants Si based Bio-MEMS applications Neuro-circuit interaction Chemical delivery Issues with long term implant bio compatibility Stanford Robo-hobo: A rat instructed via a wireless receiver and brain implant to walk along a railroad track.

5 IEEE Spectrum, Aug., 2002 EECS 509 BioMEMS Drug Delivery Bio MEMS example Science 2001, MIT Nature 1999, MIT EECS 509 BioMEMS Advantages of Microsystems Small samples -Nanoliter quantities without evaporative loss Multiplexing -Discovery biotech puts a premium on high throughput, enables genomics, proteomics Integration, Performance, Speed -Highly integrated systems possible -Many analysis method work better as they are scaled down -Scaling down dramatically improves speed of analysis Portability (small size), Low reagent and power consumption (low cost) New types of analysis, new effects to exploit -Serial chromatographies, dielectrophoresis, surface tension EECS 509 BioMEMS Limitations of Microsystems Techniques dependent on inertia are problematic -Centrifugation, mixing Physical state of analytes and carrier solvents can t change -Liquid only or gas only systems - solids clog, bubbles unstable and irreproducible -No precipitation allowed Interface with macro world -Reagent reservoirs, sample Introduction , detection Mass transfer rates are tiny -Mixing generally only occurs by diffusion Non specific binding - high surface area to volume ratio Microscale phenomena not fully understood EECS 509 BioMEMS Alternative Materials Materials requirement for BioMEMS is different from those for typical MEMS.

6 Desired properties of BioMEMS materials -Biocompatible -Chemically modifiable -Surface modifiable -Easy to fabricate -Economically viable ( for throw away devices) Si, glass and now more toward EECS 509 BioMEMS Types of BioMEMS Devices Biomaterials DNA chip cDNA, oligomer Protein chip Enzyme, antibody, antigen Cell chip Microorganism, animal cell, neuron Applications Bio-electronic device Biocomputing, bio-memory Implantable chip Prosthetic device, bioinstrumentation Lab-on-a-chip -TAS, screening Biosensor Diagnostics, analysis Microfluidics EECS 509 BioMEMS Microfluidics Characteristics Low Reynolds s Number, Re -Laminar flow -Difficult to mixing Large surface to volume ratio -Surface effect dominant bio-surface modification -Microchannel pressure drop Small fluid volume: pL to mL -Nano or micro dispenser -Diffusion Fluidic driving -Electroosmotic force -External pressure force Surface Properties and Modifications 3/10/ 2014 LNF microfluidic workshop 2014 Hydrophilic vs Hydrophobic Surface Hydrophilic: from the Greek (hydros), meaning water, and (philia), meaning love.

7 Hydrophilic substances can seem to attract water out of the air, the way salts (which are hydrophilic) do. Sugar, too, is hydrophilic, and like salt is sometimes used to draw water out of foods. A hydrophilic molecule or portion of a molecule is one that is typically charge-polarized and capable of hydrogen bonding, enabling it to dissolve more readily in water than in oil or other hydrophobic solvents. Hydrophobic: from the Attic Greek (hydro), meaning water, and phobos, meaning fear. Hydrophobicity is the physical property of a molecule (known as a hydrophobe) that is repelled from a mass of water. Hydrophobic molecules tend to be non-polar and, thus, prefer other neutral molecules and non-polar solvents. 3/10/ 2014 LNF microfluidic workshop 2014 Contact Angle - Wetting Contact angle is the angle, conventionally measured through the liquid, where a liquid/vapor interface meets a solid surface.

8 It quantifies the wettability of a solid surface by a liquid via the Young equation. A given system of solid, liquid, and vapor at a given temperature and pressure has a unique equilibrium contact angle. If the solid vapor interfacial energy is denoted by gSG, the solid liquid interfacial energy by gSL, and the liquid vapor interfacial energy ( the surface tension) by gLG, then the equilibrium contact angle qC is determined from these quantities by Young's Equation: 0 = gSG gSL + gLGcos qC 3/10/ 2014 LNF microfluidic workshop 2014 Rame-Hart 200 Contact Angle Goniometer Typical Contact Angles Contact angles are extremely sensitive to contamination; values reproducible to better than a few degrees are generally only obtained under laboratory conditions with purified liquids and very clean solid surfaces.

9 Bare metallic or ceramic surfaces: ~0o The liquid molecules are strongly attracted to the solid molecules then the liquid drop will completely spread out on the solid surface. Hydrophilic: < 90o Silicon dioxide, silicon nitride, etc. Hydrophobic: > 90o Silicon, most polymers, etc. Highly hydrophobic surfaces made of low surface energy ( fluorinated) materials may have water contact angles as high as ~120 Some materials with highly rough surfaces may have a water contact angle even greater than 150 , due to the presence of air pockets under the liquid drop. These are called super hydrophobic surfaces 3/10/ 2014 LNF microfluidic workshop 2014 How to Change the Surface Property? By coating and patterning a layer of film, you can change the surface property, especially inside a give microfluidic channel. Hydrophobic surface formation By depositing Teflon or SAM (self-assembled monolayer) coating such as FDTS.

10 Also by patterning the surface to customize hydrophobicity. Hydrophilic surface formation By plasma treatment of the surface, you can change the surface from hydrophobic to hydrophilic ( plasma treatment of PDMS). However, the surface property change is typically temporal and its property degrades over time. 3/10/ 2014 LNF microfluidic workshop 2014 Channel Patterning - Superhydrophobicity Wetting Wenzel regime are sticky in that drops of water tend to adhere to them more than a flat surface of the same type. Those following the regime of Cassie and Baxter are slippy and allow drops of water to roll off more easily than an equivalent flat surface. Hierarchical structure is necessary to have high contact angle but also essential for the stability of the composite interface (water-solid and water- air).