1、Lab on a Chip,Or:The Incredible Shrinking Science Experiment!Or:APOIBE!,Credits:Mathies Lab,UC-Berkeley Quake Lab,StanfordAgilent,Inc.,二十一世纪科学发展趋势,MiniaturizationAutomationIntegrationPortable,Lab on a Chip?,Microfluidics,Microfluidics:The use of microfabrication techniques from the IC industry to fa
2、bricate channels,chambers,reactors,and active components on the size scale of the width of a human hair or smaller,Credit:Dr.Karen Cheung,UBC ECE,Why use microfluidics?,Credit:Dr.Karen Cheung,UBC ECE1 molecule in 1 mL=1.6 x 10-18 M1 molecule in 1 nL=1.6 x 10-15 M1 molecule in 1 pL=1.6 x 10-12 M,Samp
3、le savings nL of enzyme,not mLFaster analyses can heat,cool small volumes quicklyIntegration combine lots of steps onto a single deviceNovel physics diffusion,surface tension,and surface effects dominate This can actually lead to faster reactions!,Why use microfluidics?,1-3 min/12 samples,Microchip
4、electrophoresis1-3 minMulti-channel microchip electrophoresis,High voltage,buffer,sample,capillary,10-30 min,Capillary electrophoresisseparationdetection,buffer,1-3,Gel electrophoresis,Some interesting LOC applications,Genetic analysisPortable devices for pathogen detectionHigh-throughput biologyChe
5、mical synthesisCellImmunoassay analysisMetabolite analysisDrug delivery systemsSingle molecularEnzyme analysis,Courtesy of Dr.Boris Stoeber,Genetic analysis microsystems,96-channel radial capillary array electrophoresis microplate,Anal Chem.1999;71(23):5354-61,Food poisoning,Bacterial PathogensWound
6、 infections,Biowarfare,Food poisoning:Pathogenic E.coli:1 in 10,000 in CanadaSalmonella spp.:as high as 1 in 50 eggs,Wound infections:Antibiotic-resistant S.aureus:as high as 50%Lung Disease:Pseudomonas spp.Mycobacterium tuberculosisBiowarfare:Anthrax,plague,smallpox,Lung Disease,Dr.Sharon Peacock,U
7、niversity of Oxford,Methods for Genetic Detection of Pathogens,OLD WAY:,NEW WAY:Develop bacterial pathogen detectors that are:,Rapid(1 hour)General(many different types of pathogens)Sensitive(detect a single cell)Genetically SpecificField-portable,PCR-CE Microsystem Fabrication,Portable System for I
8、nfectious Disease Detection,System measures 8 x 10 x 12 inches,Complete fluorescence detection including 488-nm solid-state laser,PMT,optics,and detection electronicsHeater and RTD electronics4 high-voltage CE power suppliesPDMS microvalve hardwareSimple PC interface,Time(seconds),rature C),Thermal
9、Cycling Characteristics,Time(seconds)5X faster than conventional thermal cyclers,Application:Tuberculosis(TB)detection,Disease caused by Mycobacterium tuberculosis9 million new cases of active TB every year worldwide 2 million TB deaths every year450,000 new cases of multi-drug resistant TB/yr10%of
10、TB cases in South Africa are XDR TB strains,resistant to first-and second-line antibioticsDoctors Without Borders:,Current TB detection methods,Fixation and staining with acid-fast stains(Ziehl-Neelsen or auramine stains)Optical or fluorescence microscope examination(10,000 organisms/mL)Culture in b
11、iosafety level 3 containment facilityIn select cases,molecular detection is used to verify diagnosisThat TB destroys millions of lives around the world every year shows that the current approach is just not workingThe tools we have to treat and diagnose TB arewoefully inadequate and outdated,and wer
12、e not seeing the necessaryurgency to tackle the disease.Dr.Tido von Schoen-Angerer,Director,DWBs Campaign for the Access to Essential Medicines,The Not-so-Distant Future,2008PDA2308?,Paramount,384根通道扫描检测,Emrich,C.A.,et al.,Analytical Chemistry,2002.74(19):p.5076-5083.,10根通道CCD同时检测,Dang,F.Q.,et al.,A
13、nalytical Chemistry,2005.77(7):p.2140-2146.,目前最高通量微流控芯片平台,Aborn,J.H.,et al.,Lab on a Chip,2005.5(6):p.669-674,门控进样多通道检测,Xu,X.M.,et al.,Analytical Chemistry,2002.74(21):p.5517-5522,高通量均相免疫分析,Bromberg,A.and R.A.Mathies,Electrophoresis,2004.25(12):p.1895-1900,Microbes,cells and small organisms come in
14、a wide array of shapes and sizesYeast,Blood Cells,cryptosporidium,Lab-on-a-chip Devices for Cell Separation and Identification,Microfluidic or Lab-on-a-chip Devices can be used to separate different cell types,Various blood cell separations have been demonstrated:J.A.Davis,D.W.Inglis,K.M.Morton,D.A.
15、Lawrence,L.R.Huang,S.Y.Chou,J.C.Sturm,andR.H.Austin,Deterministic hydrodynamics:taking blood apart,Proc.Nat.Acad.Sci.(USA),vol.103,pp.14779-14784,2006.,D.W.Inglis,J.A.Davis,T.J.Zieziulewicz,D.A.Lawrence,R.H.Austin,and J.C.Sturm,Determining blood cell size using microuidic hydrodynamics,J.Immunol.Met
16、h.,vol.329,pp.151-156,2008.D.W.Inglis,K.J.Morton,J.A.Davis,T.J.Zieziulewicz,D.A.Lawrence,R.H.Austin,and J.C.Sturm,Microfluidic device for label-free measurement of platelet activation,Submitted to Lab on a Chip,Jan 08.But no work yet with microorganisms!,This project will lead to publications which demonstrate the separation of microorganisms on portable inexpensive polymer microfluidic devices.,Such devices may have applications inearly detection of human diseases such as sepsis and various par
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