Historically, technology has been central to new discoveries in biology and progress in medicine. Among various technologies, microtechnologies, in particular, have had a prominent role in the revolution experienced by the life sciences in the last few decades, which will surely continue in the years to come. In this Perspective, we illustrate how microtechnologies, with a focus on microfluidics, have evolved in trends/waves to tackle the boundary of knowledge in the life sciences. We provide illustrative examples of technology-enabled biological breakthroughs and their current and future use in clinics. Finally, we take a closer look at the translational process to understand why the incorporation of new micro-scale technologies in medicine has been comparatively slow so far.
REFERENCES
1.
J. H.
Hurst
, “Pioneering geneticist Mary-Claire King receives the 2014 Lasker–Koshland special achievement award in medical science
,” J. Clin. Invest.
124
(10
), 4148
–4151
(2014
).2.
R. J. F.
Loos
, “15 years of genome-wide association studies and no signs of slowing down
,” Nat. Commun.
11
(1
), 10
–12
(2020
). 3.
N.
Zhu
, D.
Zhang
, W.
Wang
, X.
Li
, B.
Yang
, J.
Song
, X.
Zhao
, B.
Huang
, W.
Shi
, R.
Lu
, P.
Niu
, F.
Zhan
, X.
Ma
, D.
Wang
, W.
Xu
, G.
Wu
, G. F.
Gao
, and W.
Tan
, “A novel coronavirus from patients with pneumonia in China, 2019
,” N. Engl. J. Med.
382
(8
), 727
–733
(2020
). 4.
W. J.
Henzel
, C.
Watanabe
, and J. T.
Stults
, “Protein identification: The origins of peptide mass fingerprinting
,” J. Am. Soc. Mass Spectrom.
14
(9
), 931
–942
(2003
). 5.
C. A.
Heid
, J.
Stevens
, K. J.
Livak
, and P. M.
Williams
, “Real time quantitative PCR
,” Exp. Mol. Med.
6
, 986
–994
(1996
). 6.
B. C.
Durney
, C. L.
Crihfield
, and L. A.
Holland
, “Capillary electrophoresis applied to DNA: Determining and harnessing sequence and structure to advance bioanalyses (2009-2014)
,” Anal. Bioanal. Chem.
407
(23
), 6923
–6938
(2017
). 7.
A.
Manz
, N.
Graber
, and H. M.
Widmer
, “Miniaturized total chemical analysis systems: A novel concept for chemical sensing
,” Sens. Actuators B Chem.
B1
, 244
–248
(1990
). 8.
D. J.
Harrison
, A.
Manz
, H.
Lüdi
, H. M.
Widmer
, and Z.
Fan
, “Capillary electrophoresis and sample injection systems integrated on a planar glass chip
,” Anal. Chem.
64
(17
), 1926
–1932
(1992
). 9.
F.
Ahmad
and S. A.
Hashsham
, “Miniaturized nucleic acid amplification systems for rapid and point-of-care diagnostics: A review
,” Anal. Chim. Acta
733
, 1
–15
(2012
). 10.
A. T.
Woolley
, D.
Hadley
, P.
Landre
, A. J.
deMello
, R. A.
Mathies
, and M. A.
Northrup
, “Functional integration of PCR amplification and capillary electrophoresis in a microfabricated DNA analysis device
,” Anal. Chem.
68
(23
), 4081
–4086
(1996
). 11.
B. C.
Giordano
, J.
Ferrance
, S.
Swedberg
, A. F. R.
Hühmer
, and J. P.
Landers
, “Polymerase chain reaction in polymeric microchips: DNA amplification in less than 240 s
,” Anal. Biochem.
291
(1
), 124
–132
(2001
). 12.
M. U.
Kopp
, A. J.
Mello
, and A.
Manz
, “Chemical amplification: Continuous-flow PCR on a chip
,” Science
280
(5366
), 1046
–1048
(1998
). 13.
B.
Vogelstein
and K. W.
Kinzler
, “Digital PCR
,” Proc. Natl. Acad. Sci. U.S.A.
96
(16
), 9236
–9241
(1999
). 14.
A. A.
Morley
, “Digital PCR: A brief history
,” Biomol. Detect. Quantif.
1
(1
), 1
–2
(2014
). 15.
T.
Lenoir
and E.
Giannella
, “The emergence and diffusion of DNA microarray technology
,” J. Biomed. Discov. Collab.
1
(1
), 1
–39
(2006
). 16.
X.
Li
, R.
Quigg
, J.
Zhou
, W.
Gu
, P.
Rao
, and E.
Reed
, “Clinical utility of microarrays: Current status, existing challenges and future outlook
,” Curr. Genomics
9
(7
), 466
–474
(2008
). 17.
M.
Wiltgen
and G. P.
Tilz
, “DNA microarray analysis: Principles and clinical impact
,” Hematology
12
(4
), 271
–287
(2007
). 18.
P. L.
Ståhl
, F.
Salmén
, S.
Vickovic
, A.
Lundmark
, J. F.
Navarro
, J.
Magnusson
, S.
Giacomello
, M.
Asp
, J. O.
Westholm
, M.
Huss
, A.
Mollbrink
, S.
Linnarsson
, S.
Codeluppi
, Å.
Borg
, F.
Pontén
, P. I.
Costea
, P.
Sahlén
, J.
Mulder
, O.
Bergmann
, J.
Lundeberg
, and J.
Frisén
, “Visualization and analysis of gene expression in tissue sections by spatial transcriptomics
,” Science
353
(6294
), 78
–82
(2016
). 19.
M.
Ronaghi
, S.
Karamohamed
, B.
Pettersson
, M.
Uhlén
, and P.
Nyrén
, “Real-time DNA sequencing using detection of pyrophosphate release
,” Anal. Biochem.
242
(1
), 84
–89
(1996
). 20.
M.
Barba
, H.
Czosnek
, and A.
Hadidi
, “Historical perspective, development and applications of next-generation sequencing in plant virology
,” Viruses
6
(1
), 106
–136
(2013
). 21.
M.
Margulies
, M.
Egholm
, W. E.
Altman
, S.
Attiya
, J. S.
Bader
, L. A.
Bemben
, J.
Berka
, M. S.
Braverman
, Y. J.
Chen
, Z.
Chen
, S. B.
Dewell
, L.
Du
, J. M.
Fierro
, X. V.
Gomes
, B. C.
Godwin
, W.
He
, S.
Helgesen
, C. H.
Ho
, G. P.
Irzyk
, S. C.
Jando
, M. L. I.
Alenquer
, T. P.
Jarvie
, K. B.
Jirage
, J. B.
Kim
, J. R.
Knight
, J. R.
Lanza
, J. H.
Leamon
, S. M.
Lefkowitz
, M.
Lei
, J.
Li
, K. L.
Lohman
, H.
Lu
, V. B.
Makhijani
, K. E.
McDade
, M. P.
McKenna
, E. W.
Myers
, E.
Nickerson
, J. R.
Nobile
, R.
Plant
, B. P.
Puc
, M. T.
Ronan
, G. T.
Roth
, G. J.
Sarkis
, J. F.
Simons
, J. W.
Simpson
, M.
Srinivasan
, K. R.
Tartaro
, A.
Tomasz
, K. A.
Vogt
, G. A.
Volkmer
, S. H.
Wang
, Y.
Wang
, M. P.
Weiner
, P.
Yu
, R. F.
Begley
, and J. M.
Rothberg
, “Genome sequencing in microfabricated high-density picolitre reactors
,” Nature
437
(7057
), 376
–380
(2005
). 22.
F.
Tang
, C.
Barbacioru
, Y.
Wang
, E.
Nordman
, C.
Lee
, N.
Xu
, X.
Wang
, J.
Bodeau
, B. B.
Tuch
, A.
Siddiqui
, K.
Lao
, and M. A.
Surani
, “MRNA-Seq whole-transcriptome analysis of a single cell
,” Nat. Methods
6
(5
), 377
–382
(2009
). 23.
K.
Wetterstrand
, see www.genome.gov/sequencingcostsdata for “DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP).”24.
J. F.
Hess
, T. A.
Kohl
, M.
Kotrová
, K.
Rönsch
, T.
Paprotka
, V.
Mohr
, T.
Hutzenlaub
, M.
Brüggemann
, R.
Zengerle
, S.
Niemann
, and N.
Paust
, “Library preparation for next generation sequencing: A review of automation strategies
,” Biotechnol. Adv.
41
, 107537
(2020
). 25.
J.
Eid
, A.
Fehr
, J.
Gray
, K.
Luong
, J.
Lyle
, G.
Otto
, P.
Peluso
, D.
Rank
, P.
Baybayan
, B.
Bettman
, A.
Bibillo
, K.
Bjornson
, B.
Chaudhuri
, F.
Christians
, R.
Cicero
, S.
Clark
, R.
Dalal
, A.
DeWinter
, J.
Dixon
, M.
Foquet
, A.
Gaertner
, P.
Hardenbol
, C.
Heiner
, K.
Hester
, D.
Holden
, G.
Kearns
, X.
Kong
, R.
Kuse
, Y.
Lacroix
, S.
Lin
, P.
Lundquist
, C.
Ma
, P.
Marks
, M.
Maxham
, D.
Murphy
, I.
Park
, T.
Pham
, M.
Phillips
, J.
Roy
, R.
Sebra
, G.
Shen
, J.
Sorenson
, A.
Tomaney
, K.
Travers
, M.
Trulson
, J.
Vieceli
, J.
Wegener
, D.
Wu
, A.
Yang
, D.
Zaccarin
, P.
Zhao
, F.
Zhong
, J.
Korlach
, and S.
Turner
, “Real-time DNA sequencing from single polymerase molecules
,” Science
323
(5910
), 133
–138
(2009
). 26.
L.
Xue
, H.
Yamazaki
, R.
Ren
, M.
Wanunu
, A. P.
Ivanov
, and J. B.
Edel
, “Solid-state nanopore sensors
,” Nat. Rev. Mater.
5
(12
), 931
–951
(2020
). 27.
J. J.
Kasianowicz
, E.
Brandin
, D.
Branton
, and D. W.
Deamer
, “Characterization of individual polynucleotide molecules using a membrane channel
,” Proc. Natl. Acad. Sci. U.S.A.
93
(24
), 13770
–13773
(1996
). 28.
N.
Ashkenasy
, J.
Sánchez-Quesada
, H.
Bayley
, and M. R.
Ghadiri
, “Recognizing a single base in an individual DNA strand: A step toward DNA sequencing in nanopores
,” Angew. Chem. Int. Ed.
44
(9
), 1401
–1404
(2005
). 29.
M.
Jain
, H. E.
Olsen
, B.
Paten
, and M.
Akeson
, “The Oxford nanopore MinION: Delivery of nanopore sequencing to the genomics community
,” Genome Biol.
17
(1
), 239
(2016
). 30.
S. P.
Gygi
, Y.
Rochon
, B. R.
Franza
, and R.
Aebersold
, “Correlation between protein and MRNA abundance in yeast
,” Mol. Cell. Biol.
19
(3
), 1720
–1730
(1999
). 31.
P.
Mitchell
, “A perspective on protein microarrays
,” Nat. Biotechnol.
20
, 225
–229
(2002
). 32.
W.
Timp
and G.
Timp
, “Beyond mass spectrometry, the next step in proteomics
,” Sci. Adv.
6
(2
), 1
–17
(2020
). 33.
R.
Aebersold
, J. N.
Agar
, I. J.
Amster
, M. S.
Baker
, C. R.
Bertozzi
, E. S.
Boja
, C. E.
Costello
, B. F.
Cravatt
, C.
Fenselau
, B. A.
Garcia
, Y.
Ge
, J.
Gunawardena
, R. C.
Hendrickson
, P. J.
Hergenrother
, C. G.
Huber
, A. R.
Ivanov
, O. N.
Jensen
, M. C.
Jewett
, N. L.
Kelleher
, L. L.
Kiessling
, N. J.
Krogan
, M. R.
Larsen
, J. A.
Loo
, R. R.
Ogorzalek Loo
, E.
Lundberg
, M. J.
MacCoss
, P.
Mallick
, V. K.
Mootha
, M.
Mrksich
, T. W.
Muir
, S. M.
Patrie
, J. J.
Pesavento
, S. J.
Pitteri
, H.
Rodriguez
, A.
Saghatelian
, W.
Sandoval
, H.
Schlüter
, S.
Sechi
, S. A.
Slavoff
, L. M.
Smith
, M. P.
Snyder
, P. M.
Thomas
, M.
Uhlén
, J. E.
Van Eyk
, M.
Vidal
, D. R.
Walt
, F. M.
White
, E. R.
Williams
, T.
Wohlschlager
, V. H.
Wysocki
, N. A.
Yates
, N. L.
Young
, and B.
Zhang
, “How many human proteoforms are there?
” Nat. Chem. Biol.
14
(3
), 206
–214
(2018
). 34.
I.
Pereiro
, J. F.
Cors
, S.
Pané
, B. J.
Nelson
, and G. V.
Kaigala
, “Underpinning transport phenomena for the patterning of biomolecules
,” Chem. Soc. Rev.
48
(5
), 1236
–1254
(2019
). 35.
N.
Ramachandran
, E.
Hainsworth
, B.
Bhullar
, S.
Eisenstein
, B.
Rosen
, A. Y.
Lau
, J. C.
Walter
, and J.
LaBaer
, “Self-assembling protein microarrays
,” Science
305
(5680
), 86
–90
(2004
). 36.
M.
He
and M. J.
Taussig
, “Single step generation of protein arrays from DNA by cell-free expression and in situ immobilisation (PISA method)
,” Nucleic Acids Res.
29
(15
), e73
–e73
(2001
). 37.
B. R.
Takulapalli
, J.
Qiu
, D. M.
Magee
, P.
Kahn
, A.
Brunner
, K.
Barker
, S.
Means
, S.
Miersch
, X.
Bian
, A.
Mendoza
, F.
Festa
, K.
Syal
, J. G.
Park
, J.
Labaer
, and P.
Wiktor
, “High density diffusion-free nanowell arrays
,” J. Proteome Res.
11
(8
), 4382
–4391
(2012
). 38.
J. B.
Fenn
, M.
Mann
, C. K.
Meng
, S. F.
Wong
, and C. M.
Whitehouse
, “Electrospray ionization for mass spectrometry of large biomolecules
,” Science
246
(4926
), 64
–71
(1989
). 39.
M.
Karas
and F.
Hillenkamp
, “Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons
,” Anal. Chem.
60
(20
), 2299
–2301
(1988
). 40.
L.
Restrepo-pérez
, C.
Joo
, and C.
Dekker
, “Paving the way to single-molecule protein sequencing
,” Nat. Nanotechnol.
13
, 786
–796
(2018
). 41.
Y.
Zhao
, B.
Ashcroft
, P.
Zhang
, H.
Liu
, S.
Sen
, W.
Song
, J.
Im
, B.
Gyarfas
, S.
Manna
, S.
Biswas
, C.
Borges
, and S.
Lindsay
, “Single-molecule spectroscopy of amino acids and peptides by recognition tunnelling
,” Nat. Nanotechnol.
9
, 466
–473
(2014
). 42.
E. C.
Yusko
, B. R.
Bruhn
, O. M.
Eggenberger
, J.
Houghtaling
, R. C.
Rollings
, N. C.
Walsh
, S.
Nandivada
, M.
Pindrus
, A. R.
Hall
, D.
Sept
, J.
Li
, D. S.
Kalonia
, and M.
Mayer
, “Real-time shape approximation and fingerprinting of single proteins using a nanopore
,” Nat. Nanotechnol.
12
(4
), 360
–367
(2017
). 43.
H.
Ouldali
, K.
Sarthak
, T.
Ensslen
, F.
Piguet
, P.
Manivet
, J.
Pelta
, J. C.
Behrends
, A.
Aksimentiev
, and A.
Oukhaled
, “Electrical recognition of the twenty proteinogenic amino acids using an aerolysin nanopore
,” Nat. Biotechnol.
38
, 176
–181
(2020
). 44.
F.
Ruggeri
, F.
Zosel
, N.
Mutter
, M.
Rozycka
, M.
Wojtas
, A.
Ozyhar
, B.
Schuler
, and M.
Krishnan
, “Single-molecule electrometry
,” Nat. Nanotechnol.
12
(5
), 488
–495
(2017
). 45.
P.
Liao
and Y.
Huang
, “Digital PCR: Endless frontier of ‘divide and conquer
,’” Micromachines
8
(8
), 1
–7
(2017
). 46.
S.
Goodwin
, J. D.
McPherson
, and W. R.
McCombie
, “Coming of age: Ten years of next-generation sequencing technologies
,” Nat. Rev. Genet.
17
(6
), 333
–351
(2016
). 47.
I.
Uzoma
and H.
Zhu
, “Interactome mapping: Using protein microarray technology to reconstruct diverse protein networks
,” Genomics Proteomics Bioinf.
11
(1
), 18
–28
(2013
). 48.
K. J.
Dirico
, W.
Hua
, C.
Liu
, J. W.
Tucker
, A. S.
Ratnayake
, M. E.
Flanagan
, M. D.
Troutman
, M. C.
Noe
, and H.
Zhang
, “Ultra-high-throughput acoustic droplet ejection-open port interface-mass spectrometry for parallel medicinal chemistry
,” Med. Chem. Lett.
11
, 1101
–1110
(2020
). 49.
E. Z.
Macosko
, A.
Basu
, R.
Satija
, J.
Nemesh
, K.
Shekhar
, M.
Goldman
, I.
Tirosh
, A. R.
Bialas
, N.
Kamitaki
, E. M.
Martersteck
, J. J.
Trombetta
, D. A.
Weitz
, J. R.
Sanes
, A. K.
Shalek
, A.
Regev
, and S. A.
McCarroll
, “Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets
,” Cell
161
(5
), 1202
–1214
(2015
). 50.
J. U.
Lind
, T. A.
Busbee
, A. D.
Valentine
, F. S.
Pasqualini
, H.
Yuan
, M.
Yadid
, S. J.
Park
, A.
Kotikian
, A. P.
Nesmith
, P. H.
Campbell
, J. J.
Vlassak
, J. A.
Lewis
, and K. K.
Parker
, “Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing
,” Nat. Mater.
16
(3
), 303
–308
(2017
). 51.
S. J.
Altschuler
and L. F.
Wu
, “Cellular heterogeneity: Do differences make a difference?
” Cell
141
(4
), 559
–563
(2010
). 52.
W. A.
Bonner
, H. R.
Hulett
, R. G.
Sweet
, and L. A.
Herzenberg
, “Fluorescence activated cell sorting
,” Rev. Sci. Instrum.
43
(3
), 404
–409
(1972
). 53.
A. Y.
Fu
, C.
Spence
, A.
Scherer
, F. H.
Arnold
, and S. R.
Quake
, “A microfabricated fluorescence-activated cell sorter
,” Nat. Biotechnol.
17
(11
), 1109
–1111
(1999
). 54.
M. M.
Wang
, E.
Tu
, D. E.
Raymond
, J. M.
Yang
, H.
Zhang
, N.
Hagen
, B.
Dees
, E. M.
Mercer
, A. H.
Forster
, I.
Kariv
, P. J.
Marchand
, and W. F.
Butler
, “Microfluidic sorting of mammalian cells by optical force switching
,” Nat. Biotechnol.
23
, 83
–87
(2005
). 55.
T.
Zhang
, A. R.
Warden
, Y.
Li
, and X.
Ding
, “Progress and applications of mass cytometry in sketching immune landscapes
,” Clin. Transl. Med.
10
(6
), 1
–25
(2020
). 56.
J. B.
Dahl
, J.-M. G.
Lin
, S. J.
Muller
, and S.
Kumar
, “Microfluidic strategies for understanding the mechanics of cells and cell-mimetic systems
,” Annu. Rev. Chem. Biomol. Eng.
6
, 293
–317
(2015
). 57.
X.
Zhang
, T.
Li
, F.
Liu
, Y.
Chen
, J.
Yao
, Z.
Li
, Y.
Huang
, and J.
Wang
, “Comparative analysis of droplet-based ultra-high-throughput single-cell RNA-Seq systems
,” Mol. Cell
73
(1
), 130
–142
(2019
). 58.
M.
Stoeckius
, C.
Hafemeister
, W.
Stephenson
, B.
Houck-loomis
, P. K.
Chattopadhyay
, H.
Swerdlow
, R.
Satija
, and P.
Smibert
, “Simultaneous epitope and transcriptome measurement in single cells
,” Nat. Methods
14
(9
), 865
–868
(2017
). 59.
V. M.
Peterson
, K. X.
Zhang
, N.
Kumar
, J.
Wong
, L.
Li
, C.
Wilson
, R.
Moore
, T. K.
Mcclanahan
, S.
Sadekova
, and J. A.
Klappenbach
, “Multiplexed quantification of proteins and transcripts in single cells
,” Nat. Biotechnol.
35
(10
), 936
–939
(2017
). 60.
D. C.
Duffy
, J. C.
McDonald
, O. J. A.
Schueller
, and G. M.
Whitesides
, “Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)
,” Anal. Chem.
70
(23
), 4974
–4984
(1998
). 61.
Q.
Wu
, J.
Liu
, X.
Wang
, L.
Feng
, J.
Wu
, X.
Zhu
, and W.
Wen
, “Organ-on-a-chip : Recent breakthroughs and future prospects
,” Biomed. Eng. Online
19
, 1
–19
(2020
). 62.
P. M.
Van Midwoud
, M. T.
Merema
, E.
Verpoorte
, and G. M. M.
Groothuis
, “A microfluidic approach for in vitro assessment of interorgan interactions in drug metabolism using intestinal and liver slices
,” Lab Chip
10
(20
), 2278
–2286
(2010
). 63.
B. M.
Al-Barghouthi
and C. R.
Farber
, “Dissecting the genetics of osteoporosis using systems approaches
,” Trends Genet.
35
(1
), 55
–67
(2019
). 64.
M.-T.
Lo
, D. A.
Hinds
, J. Y.
Tung
, C.
Franz
, C.-C.
Fan
, Y.
Wang
, O. B.
Smeland
, A.
Schork
, D.
Holland
, K.
Kauppi
, N.
Sanyal
, V.
Escott-Price
, D. J.
Smith
, M.
O’Donovan
, H.
Stefansson
, G.
Bjornsdottir
, T. E.
Thorgeirsson
, K.
Stefansson
, L. K.
McEvoy
, A. M.
Dale
, O. A.
Andreassen
, and C.-H.
Chen
, “Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders
,” Nat. Genet.
49
(1
), 152
–156
(2017
). 65.
N.
Pirastu
, P. K.
Joshi
, P. S.
De Vries
, M. C.
Cornelis
, P. M.
McKeigue
, N.
Keum
, N.
Franceschini
, M.
Colombo
, E. L.
Giovannucci
, A.
Spiliopoulou
, L.
Franke
, K. E.
North
, P.
Kraft
, A. C.
Morrison
, T.
Esko
, and J. F.
Wilson
, “GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk
,” Nat. Commun.
8
(1
), 1
–9
(2017
). 66.
A.
Fernandez-Marmiesse
, S.
Gouveia
, and M. L.
Couce
, “NGS technologies as a turning point in rare disease research, diagnosis and treatment
,” Curr. Med. Chem.
25
, 404
–432
(2018
). 67.
J.
Zhang
, S. S.
Späth
, S. L.
Marjani
, W.
Zhang
, and X.
Pan
, “Characterization of cancer genomic heterogeneity by next-generation sequencing advances precision medicine in cancer treatment
,” Precis. Clin. Med.
1
(1
), 29
–48
(2018
). 68.
S.
Turajilic
, A.
Sottoriva
, T.
Graham
, and C.
Swanton
, “Resolving genetic heterogeneity in cancer
,” Nat. Rev. Genet.
20
, 404
–416
(2019
). 69.
R.
Colomer
, R.
Mondejar
, N.
Romero-Laorden
, A.
Alfranca
, F.
Sanchez-Madrid
, and M.
Quintela-Fandino
, “When should we order a next generation sequencing test in a patient with cancer?
” EClinicalMedicine
25
, 1
–9
(2020
). 70.
V.
Masciale
, G.
Grisendi
, F.
Banchelli
, R.
D’Amico
, A.
Maiorana
, P.
Sighinolfi
, A.
Stefani
, U.
Morandi
, M.
Dominici
, and B.
Aramini
, “Isolation and identification of cancer stem-like cells in adenocarcinoma and squamous cell carcinoma of the lung: A pilot study
,” Front. Oncol.
9
, 1
–12
(2019
). 71.
T.
Courau
, J.
Bonnereau
, J.
Chicoteau
, H.
Bottois
, R.
Remark
, L. A.
Miranda
, A.
Toubert
, M.
Blery
, T.
Aparicio
, M.
Allez
, and L. L.
Bourhis
, “Cocultures of human colorectal tumor spheroids with immune cells reveal the therapeutic potential of MICA/B and NKG2A targeting for cancer treatment
,” J. Immunother. Cancer
9
, 1
–14
(2019
).72.
J.
Demaret
, P.
Varlet
, J.
Trauet
, D.
Beauvais
, A.
Grossemy
, F. H. I.
Yakoub-agha
, and M.
Labalette
, “Monitoring CAR T-cells using flow cytometry
,” Cytom. Part B Clin. Cytom.
100
, 1
–7
(2020
). 73.
M.
Junkin
, A. J.
Kaestli
, Z.
Cheng
, C.
Jordi
, C.
Albayrak
, A.
Hoffmann
, and S.
Tay
, “High-content quantification of single-cell immune dynamics
,” Cell Rep.
15
(2
), 411
–422
(2016
). 74.
R. J.
Kimmerling
, G.
Lee Szeto
, J. W.
Li
, A. S.
Genshaft
, S. W.
Kazer
, K. R.
Payer
, J.
De Riba Borrajo
, P. C.
Blainey
, D. J.
Irvine
, A. K.
Shalek
, and S. R.
Manalis
, “A microfluidic platform enabling single-cell RNA-Seq of multigenerational lineages
,” Nat. Commun.
7
, 1
–7
(2016
). 75.
A.
Khamenehfar
, M. K.
Gandhi
, Y.
Chen
, D. E.
Hogge
, and P. C. H.
Li
, “Dielectrophoretic microfluidic chip enables single-cell measurements for multidrug resistance in heterogeneous acute myeloid leukemia patient samples
,” Anal. Chem.
88
(11
), 5680
–5688
(2016
). 76.
A.
Zeisel
, A. B.
Muñoz-Manchado
, S.
Codeluppi
, P.
Lönnerberg
, G.
La Manno
, A.
Juréus
, S.
Marques
, H.
Munguba
, L.
He
, C.
Betsholtz
, C.
Rolny
, G.
Castelo-Branco
, J.
Hjerling-Leffler
, and S.
Linnarsson
, “Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-Seq
,” Science
347
(6226
), 1138
–1142
(2015
). 77.
A.
Herland
, B. M.
Maoz
, D.
Das
, M. R.
Somayaji
, R.
Prantil-Baun
, R.
Novak
, M.
Cronce
, T.
Huffstater
, S. S. F.
Jeanty
, M.
Ingram
, A.
Chalkiadaki
, D.
Benson Chou
, S.
Marquez
, A.
Delahanty
, S.
Jalili-Firoozinezhad
, Y.
Milton
, A.
Sontheimer-Phelps
, B.
Swenor
, O.
Levy
, K. K.
Parker
, A.
Przekwas
, and D. E.
Ingber
, “Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips
,” Nat. Biomed. Eng.
4
(4
), 421
–436
(2020
). 78.
B.
Zhang
, A.
Korolj
, B.
Fook
, L.
Lai
, and M.
Radisic
, “Advances in organ-on-a-chip engineering
,” Nat. Rev. Mater.
3
, 257
–278
(2018
). 79.
K. H.
Benam
, R.
Novak
, J.
Nawroth
, M.
Hirano-Kobayashi
, T. C.
Ferrante
, Y.
Choe
, R.
Prantil-Baun
, J. C.
Weaver
, A.
Bahinski
, K. K.
Parker
, and D. E.
Ingber
, “Matched-comparative modeling of normal and diseased human airway responses using a microengineered breathing lung chip
,” Cell Syst.
3
(5
), 456
–466
(2016
). 80.
B.
Deleglise
, S.
Magnifico
, E.
Duplus
, P.
Vaur
, V.
Soubeyre
, M.
Belle
, M.
Vignes
, J. L.
Viovy
, E.
Jacotot
, J. M.
Peyrin
, and B.
Brugg
, “Β-Amyloid induces a dying-back process and remote trans-synaptic alterations in a microfluidic-based reconstructed neuronal network
,” Acta Neuropathol. Commun.
2
(1
), 1
–9
(2014
). 81.
F.
Gullo
, I.
Manfredi
, M.
Lecchi
, G.
Casari
, E.
Wanke
, and A.
Becchetti
, “Multi-electrode array study of neuronal cultures expressing nicotinic (Β2-V287L subunits, linked to autosomal dominant nocturnal frontal lobe epilepsy. An in vitro model of spontaneous epilepsy
,” Front. Neural Circuits
8
, 1
–12
(2014
). 82.
J.-P.
Frimat
and R.
Luttge
, “The need for physiological micro-nanofluidic systems of the brain
,” Front. Bioeng. Biotechnol.
7
, 1
–11
(2019
). 83.
C. W.
Shields
, K. A.
Ohiri
, L. M.
Szott
, and G. P.
López
, “Translating microfluidics: Cell separation technologies and their barriers to commercialization
,” Cytom. Part B Clin. Cytom.
92
(2
), 115
–125
(2017
). 84.
D. R.
Reyes
, H.
van Heeren
, S.
Guha
, L.
Herbertson
, A. P.
Tzannis
, J.
Ducrée
, H.
Bissig
, and H.
Becker
, “Accelerating innovation and commercialization through standardization of microfluidic-based medical devices
,” Lab Chip
21
(1
), 9
–21
(2021
). 85.
I.
Pereiro
, A.
Fomitcheva Khartchenko
, L.
Petrini
, and G. V.
Kaigala
, “Nip the bubble in the bud: A guide to avoid gas nucleation in microfluidics
,” Lab Chip
19
(14
), 2296
–2314
(2019
). 86.
C. M.
Christensen
, The Innovator’s Dilemma When New Technologies Cause Great Firms to Fail
(Harvard Business School Press
, Boston
, MA
, 1997
).87.
M.
Béjean
and E.
Siqueira
, “Organizing Medtech innovation with concept maturity levels
,” in Proceedings of the 12th International Joint Conference on Biomedical Engineering Systems and Technologies
(SCITEPRESS, 2019
), pp. 621
–626
. 88.
A. G.
Sacher
, C.
Paweletz
, S. E.
Dahlberg
, R. S.
Alden
, A.
O’Connell
, N.
Feeney
, S. L.
Mach
, P. A.
Jänne
, and G. R.
Oxnard
, “Prospective validation of rapid plasma genotyping for the detection of EGFR and KRAS mutations in advanced lung cancer
,” JAMA Oncol.
2
(8
), 1014
–1022
(2016
). 89.
A.
Grifoni
, D.
Weiskopf
, S. I.
Ramirez
, J.
Mateus
, J. M.
Dan
, C. R.
Moderbacher
, S. A.
Rawlings
, A.
Sutherland
, L.
Premkumar
, R. S.
Jadi
, D.
Marrama
, A. M.
de Silva
, A.
Frazier
, A. F.
Carlin
, J. A.
Greenbaum
, B.
Peters
, F.
Krammer
, D. M.
Smith
, S.
Crotty
, and A.
Sette
, “Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals
,” Cell
181
(7
), 1489
–1501
(2020
). 90.
W.
Wang
, B.
Su
, L.
Pang
, L.
Qiao
, Y.
Feng
, Y.
Ouyang
, X.
Guo
, H.
Shi
, F.
Wei
, X.
Su
, J.
Yin
, R.
Jin
, and D.
Chen
, “High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients
,” Cell. Mol. Immunol.
17
(6
), 650
–652
(2020
). 91.
M.
Zhang
, P.
Wang
, R.
Luo
, Y.
Wang
, Z.
Li
, Y.
Guo
, Y.
Yao
, M.
Li
, T.
Tao
, W.
Chen
, J.
Han
, H.
Liu
, K.
Cui
, X.
Zhang
, Y.
Zheng
, and J.
Qin
, “Biomimetic human disease model of SARS-CoV-2-induced lung injury and immune responses on organ chip system
,” Adv. Sci.
8
(3
), 2002928
(2020
). 92.
C.
Tymm
, J.
Zhou
, A.
Tadimety
, A.
Burklund
, and J. X. J.
Zhang
, “Scalable COVID-19 detection enabled by lab-on-chip biosensors
,” Cell. Mol. Bioeng.
13
(4
), 313
–329
(2020
). 93.
I.
Pereiro
, A.
Fomitcheva-Khartchenko
, and G. V.
Kaigala
, “Shake it or shrink it: Mass transport and kinetics in surface bioassays using agitation and microfluidics
,” Anal. Chem.
92
(15
), 10187
–10195
(2020
). 94.
E. V.
Valckenborgh
, A.
Hébrant
, A.
Antoniou
, W. V.
Hoof
, J. V.
Bussel
, P.
Pauwels
, R.
Salgado
, W. V.
Doren
, A.
Waeytens
, and M. V. D.
Bulcke
, “Roadbook for the implementation of next-generation sequencing in clinical practice in oncology and hemato-oncology in Belgium
,” Arch. Public Heal.
76
(49
), 1
–7
(2018
). 95.
S.
Shrivastava
, T. Q.
Trung
, and N. E.
Lee
, “Recent progress, challenges, and prospects of fully integrated mobile and wearable point-of-care testing systems for self-testing
,” Chem. Soc. Rev.
49
, 1812
–1866
(2020
). © 2021 Author(s). Published under an exclusive license by AIP Publishing.
2021
Author(s)
You do not currently have access to this content.