香港中文大学：《CMSC5719 Seminar》课程教学资源（讲义）Lecture 11 Design of Microfluidics-Based Biochips

Design of Microfluidics-Based Biochips Evangeline F.Y.Young Mixed Droplet Photodiode Electrical Pad LED Mixing Sample Electrowetting Electrode Reagent Slides partly adopted from Krishnendu Chakrabarty of Duke University 1

Design of Microfluidics-Based Biochips Evangeline F.Y. Young Slides partly adopted from Krishnendu Chakrabarty of Duke University 1 Slides partly adopted from Krishnendu Chakrabarty of Duke University

Motivation for Biochips Clinical diagnostics,e.g.,healthcare for premature infants,point-of-care diagnosis of diseases "Bio-smoke alarm":environmental monitoring Massive parallel DNA analysis,automated drug discovery,protein crystallization CLINICAL DIAGNOSTIC Lab-on-a-chip for APPLICATION CLINICAL DIAGNOSTICS Shrink Microfluidic Lab- on-a-Chip HttitiHitii 20nl sample Higher throughput,minimal human intervention, smaller sample/reagent consumption,higher Conventional Biochemical Analyzer sensitivity,increased productivity 2

Motivation for Biochi p s • Clinical diagnostics, e.g., healthcare for premature infants, point-of-care diagnosis of diseases • “Bio-smoke alarm”: environmental monitoring • Massive parallel DNA analysis, automated dru g y, p y discovery, protein cr ystallization Shrink CLINICAL DIAGNOSTIC APPLICATION Lab-on-a-chip for CLINICAL DIAGNOSTICS Microfluidic Lab￾on-a-Chip 20nl sam ple Conventional Biochemical Analyzer Higher throughput, minimal human intervention, smaller sample/reagent consumption, higher sensitivity, increased productivity 2 Conventional Biochemical Analyzer sensitivity, increased productivity

Motivation for Biochips Disease related mortality is the No.1 bottleneck for Aquaculture industry. Biochip can be used for fish disease testing. Laboratory Biochip Sample Processing 1 hr 30 min 5min PCR Response 3hr 1 hr 15 min Analysis 30 min 10 min Total 5hr 1 hr 30 min

Motivation for Biochi p s • Disease related mortality is the N 1 b ttl k f A lt No. 1 b ottlenec k for Aquaculture industry. • Biochip can be used for fish Biochip can be used for fish disease testing. L ba boratory Bi hi oc p Sample Processing PCR Response 1 hr 30 min 3 hr 5 min 1 hr 15 min Response Analysis Total 30 min 5 hr 10 min 1 hr 30 min

Tubes to Chips:BioChips Driven by biomolecular analysis needs Agilent DNA analysis Lab on a Chip(1997) Test tube analysis 4

Tubes to Chip p s: BioChips • Driven by biomolecular analysis needs T tt b l i Agilent DNA analysis Lab on a Chip (1997) 4 Test tube analysis

Motivation for Microfluidics ▣Automation Test tubes ▣Integration ☐Miniaturization Automation Robotics Integration ▣Miniaturization Automation Microfluidics Integration ☒Miniaturization 5

Motivation for Microfluidics T tt b Automation Test tu bes Integration Miniaturization Robotics Automation Integration Miniaturization Microfluidics Automation Integration Miniaturization 5

Typical Biological Lab Functions ·Synthesis ·Analysis A A+B◆ B A+B Mixing Reaction Separation 6

Typ g ical Biological Lab Functions • Synthesis • Analysis A B C A B A + B A + B Mixing Reaction Separation 6

Microfluidics 。 Continuous-flow biochips:Permanently etched microchannels, micropumps and microvalves Digital microfluidic biochips:Manipulation of liquids as discrete droplets ELECTRODES GLASS (Duke University) SLCON Mixed Droplet Photodiode 2002 PC BOARD Electrical Pad GEL CHANNELS 86 PHOTODETECTORS WIRE BONDS HEATERS 88 LED ELUIDIC CHANNELS Mixing Sample AIR VENTS Electrowetting Electrode Reagent Control AIR LINES (University of Michigan) electronics 1998 (shown)are suitable for Printed circuit board eWI到 handheld or lab-on-a-chip- benchtop inexpensive and applications readily manufacturable 1111111期 7

Microfluidics • Continuous-flow biochips: Permanently etched microchannels, micropumps and microvalves • Digital microfluidic biochips: Manipulation of liquids as discrete droplets (Duke University) 2002 (University of Michigan) 1998 Control electronics (shown) are suitable for suitable for handheld or benchtop applications Printed circuit board lab-on-a-chip – inexpensive and readily manufacturable 7

What is Digital Microfluidics? Discretizing the bottom electrode into multiple electrodes,we can achieve lateral droplet movement Continuous Electrode Top Plate Discrete Electrodes Note:oil is typically used to fill between the Droplet Transport(Side View) top and bottom plates to prevent evaporation. 8

What is Digital Microfluidics? • Discretizing the bottom electrode into multiple electrodes, we can achieve lateral droplet movement achieve lateral droplet movement Note: oil is typically used to fill between the Droplet Transport (Side View) t d b tt l t t t ti 8 top and bottom plates to prevent evaporation

What is Digital Microfluidics? Transport 25 cm/s flow rates, order of magnitude higher than continuous-flow methods For videos,go to www.ee.duke.edu/research/microfluidics 9

What is Digital Microfluidics? Transport 25 cm/s flow rates, order of magnitude higher than higher than continuous-flow methods F id t d k d / h/ i fl idi 9 For videos, go to www.ee.duke.edu/research/microfluidics

What is Digital Microfluidics? Splitting/Merging 10

What is Digital Microfluidics? Splitting/Merging 10