title: When Medicine Meets Engineering-Paradigm Shifts in Diagnostics and Therapeutics.
abstract: During the last two decades, the manufacturing techniques of microfluidics-based devices have been phenomenally advanced, offering unlimited potential for bio-medical technologies. However, the direct applications of these technologies toward diagnostics and therapeutics are still far from maturity. The present challenges lay at the interfaces between the engineering systems and the biocomplex systems. A precisely designed engineering system with narrow dynamic range is hard to seamlessly integrate with the adaptive biological system in order to achieve the design goals. These differences remain as the roadblock between two fundamentally non-compatible systems. This paper will not extensively review the existing microfluidic sensors and actuators; rather, we will discuss the sources of the gaps for integration. We will also introduce system interface technologies for bridging the differences to lead toward paradigm shifts in diagnostics and therapeutics.
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Hann
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Aleidy
authors.initials: A
authors.lastname: Silva
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. chihming@seas.ucla.edu.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Ho
keywords: MEMS transducers; combinatorial drugs; feedback system control (FSC); microfluidic system; network medicine
references.citation: Nat Biotechnol. 2004 Oct;22(10):1253-9
references.pmid: 15470465
references.citation: Science. 2004 Oct 22;306(5696):640-3
references.pmid: 15499008
references.citation: Anal Chem. 2001 May 1;73(9):2048-53
references.pmid: 11354489
references.citation: Science. 2000 Mar 17;287(5460):1964-9
references.pmid: 10720315
references.citation: Nature. 2009 Feb 12;457(7231):910-4
references.pmid: 19212411
references.citation: Anal Chem. 2005 Jan 15;77(2):534-40
references.pmid: 15649050
references.citation: J Proteome Res. 2004 Mar-Apr;3(2):179-96
references.pmid: 15113093
references.citation: Nat Rev Genet. 2009 Jan;10(1):57-63
references.pmid: 19015660
references.citation: Nat Rev Genet. 2001 Dec;2(12):930-42
references.pmid: 11733746
references.citation: Int J Nanomedicine. 2012;7:2281-92
references.pmid: 22654513
references.citation: J Cell Biol. 2003 Mar 3;160(5):629-33
references.pmid: 12615908
references.citation: Science. 2009 Apr 10;324(5924):218-23
references.pmid: 19213877
references.citation: Nat Rev Genet. 2005 Feb;6(2):95-108
references.pmid: 15716906
references.citation: Anal Chem. 1999 Nov 15;71(22):5054-9
references.pmid: 10575961
references.citation: Proc Natl Acad Sci U S A. 2007 May 22;104(21):8685-90
references.pmid: 17502601
references.citation: Nat Chem Biol. 2007 Apr;3(4):187-91
references.pmid: 17372598
references.citation: Anal Chem. 1998 Dec 1;70(23):4974-84
references.pmid: 21644679
references.citation: Nat Biotechnol. 2008 Oct;26(10):1146-53
references.pmid: 18846088
references.citation: Proteomics. 2012 May;12(9):1310-8
references.pmid: 22589180
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5105-10
references.pmid: 18356295
references.citation: Nat Biotechnol. 2009 Sep;27(9):847-50
references.pmid: 19668243
references.citation: Adv Biochem Eng Biotechnol. 2007;106:19-39
references.pmid: 17728993
references.citation: Nat Methods. 2009 Jan;6(1):71-4
references.pmid: 19098921
references.citation: Lab Chip. 2010 Apr 7;10(7):828-31
references.pmid: 20379565
references.citation: Science. 2003 Jan 31;299(5607):682-6
references.pmid: 12560545
references.citation: PLoS One. 2009 Aug 20;4(8):e6703
references.pmid: 19693272
references.citation: Chem Soc Rev. 2010 Mar;39(3):1153-82
references.pmid: 20179830
references.citation: Science. 1999 Apr 2;284(5411):92-6
references.pmid: 10102825
references.citation: Trends Biotechnol. 2006 Dec;24(12):580-6
references.pmid: 17055093
references.citation: Methods Mol Biol. 2011;699:179-202
references.pmid: 21116984
references.citation: J Cell Biol. 2001 Oct 15;155(2):181-5
references.pmid: 11604416
references.citation: Genome Res. 2008 Sep;18(9):1509-17
references.pmid: 18550803
references.citation: RNA Biol. 2009 Apr-Jun;6(2):107-12
references.pmid: 19875928
references.citation: Annu Rev Biomed Eng. 2002;4:261-86
references.pmid: 12117759
references.citation: Anal Biochem. 2009 Aug 1;391(1):17-23
references.pmid: 19435595
references.citation: Science. 2002 Oct 18;298(5593):580-4
references.pmid: 12351675
references.citation: Nat Nanotechnol. 2007 Apr;2(4):209-15
references.pmid: 18654264
references.citation: Nature. 2006 Jul 27;442(7101):403-11
references.pmid: 16871208
references.citation: Wiley Interdiscip Rev Syst Biol Med. 2011 Nov-Dec;3(6):619-27
references.pmid: 21928407
references.citation: Nat Rev Genet. 2010 Jan;11(1):31-46
references.pmid: 19997069
references.citation: Clin Cancer Res. 2009 Jan 15;15(2):431-40
references.pmid: 19147747
references.citation: Nature. 2002 Jan 31;415(6871):530-6
references.pmid: 11823860
references.citation: Biosens Bioelectron. 2004 Jan 15;19(6):537-46
references.pmid: 14683637
references.citation: N Engl J Med. 2007 Jul 26;357(4):404-7
references.pmid: 17652657
references.citation: J Mass Spectrom. 2009 May;44(5):579-93
references.pmid: 19373851
references.citation: Annu Rev Biomed Eng. 2002;4:129-53
references.pmid: 12117754
references.citation: Electrophoresis. 2000 Jan;21(1):27-40
references.pmid: 10634468
references.citation: Anal Bioanal Chem. 2009 Mar;393(5):1407-16
references.pmid: 18807017
references.citation: Small. 2011 Jan 3;7(1):12-48
references.pmid: 21072867
references.citation: Anal Chem. 2004 Aug 15;76(16):4833-8
references.pmid: 15307795
references.citation: Nat Rev Genet. 2011 Jan;12(1):56-68
references.pmid: 21164525
references.citation: Curr Opin Biotechnol. 2010 Aug;21(4):566-71
references.pmid: 20709523
references.citation: Nat Rev Neurosci. 2012 Jun 20;13(7):453-64
references.pmid: 22714018
references.citation: Nat Commun. 2011 Jan 25;2:167
references.pmid: 21266967
references.citation: Anal Chem. 2011 Nov 1;83(21):8073-7
references.pmid: 21981444
references.citation: FEBS Lett. 2008 Apr 9;582(8):1266-70
references.pmid: 18282479
references.citation: Am J Hum Genet. 2008 Mar;82(3):696-711
references.pmid: 18319075
references.citation: Curr Opin Biotechnol. 2011 Feb;22(1):59-65
references.pmid: 20832278
references.citation: Curr Opin Biotechnol. 2010 Aug;21(4):517-23
references.pmid: 20829028
references.citation: Anal Bioanal Chem. 2006 Jun;385(3):474-85
references.pmid: 16534574
references.citation: N Engl J Med. 2012 Mar 8;366(10):883-92
references.pmid: 22397650
references.citation: Circulation. 2005 Jan 18;111(2):212-21
references.pmid: 15630028
references.citation: Nat Biotechnol. 2012 Apr 10;30(4):326-8
references.pmid: 22491281
references.citation: Lab Chip. 2012 Apr 7;12(7):1378-83
references.pmid: 22361780
references.citation: JAMA. 2001 Feb 7;285(5):540-4
references.pmid: 11176855
references.citation: Nature. 2008 Apr 17;452(7189):872-6
references.pmid: 18421352
references.citation: Science. 2009 Jan 2;323(5910):133-8
references.pmid: 19023044
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20173-8
references.pmid: 19075237
references.citation: Anal Chem. 2010 Feb 1;82(3):1012-9
references.pmid: 20055494
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18650-5
references.pmid: 19841254
references.citation: Nature. 2001 Feb 15;409(6822):928-33
references.pmid: 11237013
references.citation: Mol Cell Biomech. 2009 Mar;6(1):1-55
references.pmid: 19382535
references.citation: Proc Am Thorac Soc. 2011 May;8(2):196-8
references.pmid: 21543801
references.citation: Nat Rev Genet. 2010 Jun;11(6):415-25
references.pmid: 20479773
references.citation: Anal Chim Acta. 2009 Oct 19;653(1):23-35
references.pmid: 19800473
references.citation: Clin Immunol. 2004 Mar;110(3):206-21
references.pmid: 15047199
references.citation: Cancer Prev Res (Phila). 2011 Jun;4(6):803-17
references.pmid: 21636547
references.citation: Nat Med. 2001 Feb;7(2):245-8
references.pmid: 11175858
references.citation: Science. 2000 Mar 17;287(5460):1960-4
references.pmid: 10720314
references.citation: Nat Rev Genet. 2011 Mar;12(3):224
references.pmid: 21301471
references.citation: Blood. 2007 Oct 1;110(7):2674-84
references.pmid: 17622571
references.citation: Biomicrofluidics. 2009 May 04;3(2):22407
references.pmid: 19693342
references.citation: J Pathol. 2002 Jan;196(1):1-7
references.pmid: 11748635
references.citation: Pediatr Res. 2010 May;67(5):458-68
references.pmid: 20075759
references.citation: Lancet. 2004 Jul 3-9;364(9428):29-34
references.pmid: 15234853
references.citation: Chem Rev. 1996 Dec 19;96(8):3147-3176
references.pmid: 11848856
references.citation: Annu Rev Biochem. 1992;61:977-1010
references.pmid: 1497328
references.citation: Mol Cell Proteomics. 2002 Nov;1(11):845-67
references.pmid: 12488461
references.citation: Nat Methods. 2010 Jun;7(6):461-5
references.pmid: 20453866
references.citation: BMC Syst Biol. 2011 May 30;5:88
references.pmid: 21624115
references.citation: Nat Rev Drug Discov. 2002 Nov;1(11):882-94
references.pmid: 12415248
references.citation: Trends Biotechnol. 2009 Oct;27(10):572-81
references.pmid: 19709772
references.citation: Nat Nanotechnol. 2011 Sep 18;6(10):615-24
references.pmid: 21926981
references.citation: Curr Opin Chem Biol. 2003 Feb;7(1):55-63
references.pmid: 12547427
references.citation: Med Res Rev. 2000 May;20(3):189-96
references.pmid: 10797463
references.citation: Nat Methods. 2011 Apr;8(4 Suppl):S20-9
references.pmid: 21451513
references.citation: Anal Chim Acta. 2011 Feb 14;687(1):12-27
references.pmid: 21241842
references.citation: Immunol Rev. 2006 Apr;210:208-28
references.pmid: 16623773
references.citation: Cell Host Microbe. 2010 Feb 18;7(2):90-9
references.pmid: 20159614
references.citation: Drug Discov Today. 2005 Jul 1;10(13):895-907
references.pmid: 15993809
references.citation: Nat Biotechnol. 2008 Oct;26(10):1135-45
references.pmid: 18846087
references.citation: Nature. 2001 Feb 15;409(6822):853-5
references.pmid: 11237009
references.citation: Small. 2009 Aug 3;5(15):1784-90
references.pmid: 19384878
references.citation: Nature. 2003 Mar 13;422(6928):208-15
references.pmid: 12634794
references.citation: Curr Opin Biotechnol. 2008 Feb;19(1):4-9
references.pmid: 18207731
references.citation: Annu Rev Biophys Biomol Struct. 2007;36:213-31
references.pmid: 17269901
references.citation: Nat Genet. 1999 Jan;21(1 Suppl):48-50
references.pmid: 9915501
references.citation: Nature. 2010 Oct 28;467(7319):1061-73
references.pmid: 20981092
references.citation: Mol Cell Biol. 1999 Mar;19(3):1720-30
references.pmid: 10022859
references.citation: Cancer Cell. 2002 Mar;1(2):133-43
references.pmid: 12086872
references.citation: Hum Mol Genet. 2010 Oct 15;19(R2):R227-40
references.pmid: 20858600
references.citation: Anal Chim Acta. 2007 Oct 10;601(2):141-55
references.pmid: 17920386
references.citation: Science. 1999 Apr 2;284(5411):99-101
references.pmid: 10102827
references.citation: Nat Biotechnol. 2000 Jun;18(6):630-4
references.pmid: 10835600
references.citation: Lab Chip. 2006 Sep;6(9):1125-39
references.pmid: 16929391
references.citation: Nature. 2011 Feb 10;470(7333):198-203
references.pmid: 21307932
references.citation: Trends Biotechnol. 2010 Jun;28(6):281-90
references.pmid: 20434785
references.citation: Nat Chem Biol. 2006 Sep;2(9):458-66
references.pmid: 16921358
references.citation: Nature. 2006 Jul 27;442(7101):368-73
references.pmid: 16871203
references.citation: Nature. 2001 Feb 15;409(6822):860-921
references.pmid: 11237011