High-quality-factor (Q) optical microcavities have attracted extensive interest due to their unique ability to confine light for resonant circulation at the micrometer scale. Particular attention has been paid to optical whispering-gallery mode (WGM) microcavities to harness their strong light–matter interactions for biological applications. Remarkably, the combination of high-Q optical WGM microcavities with microfluidic technologies can achieve a synergistic effect in the development of high-sensitivity optofluidic sensors for many emerging biological analysis applications, such as the detection of proteins, nucleic acids, viruses, and exosomes. They can also be utilized to investigate the behavior of living cells in human organisms, which may provide new technical solutions for studies in cell biology and biophysics. In this paper, we briefly review recent progress in high-Q microcavity-based optofluidic sensor technologies and their applications in biological analysis.
REFERENCES
1.
K. J.
Vahala
, “Optical microcavities
,” Nature
424
(6950
), 839
–846
(2003
). 2.
H.
Mabuchi
and A. J. S.
Doherty
, “Cavity quantum electrodynamics: Coherence in context
,” Science
298
(5597
), 1372
–1377
(2002
). 3.
X.
Jiang
et al, “Chaos-assisted broadband momentum transformation in optical microresonators
,” Science
358
(6361
), 344
–347
(2017
). 4.
X.
Zhang
et al, “Symmetry-breaking-induced nonlinear optics at a microcavity surface
,” Nat. Photonics
13
(1
), 21
–24
(2019
). 5.
P.
Del’Haye
et al, “Optical frequency comb generation from a monolithic microresonator
,” Nature
450
(7173
), 1214
–1217
(2007
). 6.
F.
Vollmer
, D.
Braun
, A.
Libchaber
, M.
Khoshsima
, I.
Teraoka
, and S.
Arnold
, “Protein detection by optical shift of a resonant microcavity
,” Appl. Phys. Lett.
80
(21
), 4057
–4059
(2002
). 7.
S.
Arnold
, M.
Khoshsima
, I.
Teraoka
, S.
Holler
, and F. J.
Vollmer
, “Shift of whispering-gallery modes in microspheres by protein adsorption
,” Opt. Lett.
28
(4
), 272
–274
(2003
). 8.
Ramachandran et al.
, “A universal biosensing platform based on optical micro-ring resonators
,” Biosens. Bioelectron.
23
(7
), 939
–944
(2008
). 9.
M. R.
Foreman
, J. D.
Swaim
, and F.
Vollmer
, “Whispering gallery mode sensors
,” Adv. Opt. Photonics
7
(2
), 168
–240
(2015
). 10.
Z.
Yuan
, Z.
Wang
, P.
Guan
, X.
Wu
, and Y. C.
Chen
, “Lasing-encoded microsensor driven by interfacial cavity resonance energy transfer
,” Adv. Opt. Mater.
8
(7
), 1901596
(2020
). 11.
A. L.
Washburn
, L. C.
Gunn
, and R. C.
Bailey
, “Label-free quantitation of a cancer biomarker in complex media using silicon photonic microring resonators
,” Anal. Chem.
81
(22
), 9499
–9506
(2009
). 12.
M.
Iqbal
et al, “Label-free biosensor arrays based on silicon ring resonators and high-speed optical scanning instrumentation
,” IEEE J. Sel. Top. Quantum Electron.
16
(3
), 654
–661
(2010
). 13.
M. A.
Santiago-Cordoba
, S. V.
Boriskina
, F.
Vollmer
, and M. C.
Demirel
, “Nanoparticle-based protein detection by optical shift of a resonant microcavity
,” Appl. Phys. Lett.
99
(7
), 073701
(2011
). 14.
M. S.
Luchansky
, A. L.
Washburn
, M. S.
McClellan
, and R. C.
Bailey
, “Sensitive on-chip detection of a protein biomarker in human serum and plasma over an extended dynamic range using silicon photonic microring resonators and sub-micron beads
,” Lab Chip
11
(12
), 2042
–2044
(2011
). 15.
T.
Taniguchi
et al, “Detection of antibody-antigen reaction by silicon nitride slot-ring biosensors using protein G
,” Opt. Commun.
365
, 16
–23
(2016
). 16.
V.
Dantham
, S.
Holler
, V.
Kolchenko
, Z.
Wan
, and S. J.
Arnold
, “Taking whispering gallery-mode single virus detection and sizing to the limit
,” Appl. Phys. Lett.
101
(4
),
043704
(2012
). 17.
F.
Vollmer
, S.
Arnold
, and D.
Keng
, “Single virus detection from the reactive shift of a whispering-gallery mode
,” Proc. Natl. Acad. Sci. U.S.A.
105
(52
), 20701
–20704
(2008
). 18.
R.
Duan
, Y.
Li
, H.
Li
, and J. J.
Yang
, “Detection of heavy metal ions using whispering gallery mode lasing in functionalized liquid crystal microdroplets
,” Biomed. Opt. Express
10
(12
), 6073
–6083
(2019
). 19.
K. D.
Heylman
, K. A.
Knapper
, E. H.
Horak
, M. T.
Rea
, S. K.
Vanga
, and R. H.
Goldsmith
, “Optical microresonators for sensing and transduction: A materials perspective
,” Adv. Mater.
29
, 1700037
(2017
). 20.
X.
Ouyang
et al, “Ultrasensitive optofluidic enzyme-linked immunosorbent assay by on-chip integrated polymer whispering-gallery-mode microlaser sensors
,” Lab Chip
20
(14
), 2438
–2446
(2020
). 21.
J.
Zhang
et al, “Whispering-gallery nanocavity plasmon-enhanced Raman spectroscopy
,” Sci. Rep.
5
, 15012
(2015
). 22.
Y.
Wang
et al, “Demonstration of intracellular real-time molecular quantification via FRET-enhanced optical microcavity
,” Nat. Commun.
13
(1
), 6685
(2022
). 23.
M. C.
Houghton
, N. A.
Toropov
, D.
Yu
, S.
Bagby
, and F.
Vollmer
, “Single molecule thermodynamic penalties applied to enzymes by whispering gallery mode biosensors
,” Adv. Sci.
2403195
(published online) (2024
). 24.
S. J.
Tang
et al, “Single-particle photoacoustic vibrational spectroscopy using optical microresonators
,” Nat. Photonics
17
(11
), 951
–956
(2023
). 25.
Z.
Guo
et al, “Hyperboloid-drum microdisk laser biosensors for ultrasensitive detection of human IgG
,” Small
16
(26
), 2000239
(2020
). 26.
E.
Ozgur
et al, “Ultrasensitive detection of human chorionic gonadotropin using frequency locked microtoroid optical resonators
,” Anal. Chem.
91
(18
), 11872
–11878
(2019
). 27.
K.
De Vos
, I.
Bartolozzi
, E.
Schacht
, P.
Bienstman
, and R. J.
Baets
, “Silicon-on-insulator microring resonator for sensitive and label-free biosensing
,” Opt. Express
15
(12
), 7610
–7615
(2007
). 28.
S.
Wu
, Y.
Guo
, W.
Wang
, J.
Zhou
, and Q.
Zhang
, “Label-free biosensing using a microring resonator integrated with poly-(dimethylsiloxane) microfluidic channels
,” Rev. Sci. Instrum.
90
(3
), 035004 (2019
).29.
E.
Kim
, M. D.
Baaske
, I.
Schuldes
, P. S.
Wilsch
, and F.
Vollmer
, “Label-free optical detection of single enzyme-reactant reactions and associated conformational changes
,” Sci. Adv.
3
(3
), e1603044
(2017
). 30.
Y. J.
Chen
, U.
Schoeler
, C. H.
Huang
, and F. J.
Vollmer
, “Combining whispering-gallery mode optical biosensors with microfluidics for real-time detection of protein secretion from living cells in complex media
,” Small
14
(22
), 1703705
(2018
). 31.
J.
Sun
et al, “Construction of a microcavity-based microfluidic chip with simultaneous SERS quantification of dual biomarkers for early diagnosis of Alzheimer’s disease
,” Talanta
261
, 124677
(2023
). 32.
H.
Ghali
, H.
Chibli
, J. L.
Nadeau
, P.
Bianucci
, and Y.-A.
Peter
, “Real-time detection of Staphylococcus aureus using whispering gallery mode optical microdisks
,” Biosensors
6
(2
), 20
(2016
). 33.
Y.
Kim
and H.
Lee
, “On-chip label-free biosensing based on active whispering gallery mode resonators pumped by a light-emitting diode
,” Optics Express
27
(23
), 34405
–34415
(2019
). 34.
M. D.
Goede
et al, “Al2O3: Yb3+ integrated microdisk laser label-free biosensor
,” Opt. Lett.
44
(24
), 5937
–5940
(2019
). 35.
E.
Ozgur
, P.
Toren
, O.
Aktas
, E.
Huseyinoglu
, and M.
Bayindir
, “Label-free biosensing with high selectivity in complex media using microtoroidal optical resonators
,” Sci. Rep.
5
(1
), 13173
(2015
). 36.
S.
Suebka
, P.-D.
Nguyen
, A.
Gin
, and J.
Su
, “How fast it can stick: Visualizing flow delivery to microtoroid biosensors
,” ACS Sens.
6
(7
), 2700
–2708
(2021
). 37.
Y.
Wang
, H.
Zhang
, Y.
Cui
, W.
Lin
, B.
Liu
, and D.
Xiang
, “Real-time conformational change monitoring of G-quadruplex using capillary-based biocompatible whispering gallery mode microresonator
,” IEEE Sens. J.
20
(21
), 12558
–12564
(2020
). 38.
J. D.
Suter
et al, “Label-free quantitative DNA detection using the liquid core optical ring resonator
,” Biosens. Bioelectron.
23
(7
), 1003
–1009
(2008
). 39.
H.
Zhu
, I. M.
White
, J. D.
Suter
, P. S.
Dale
, and X.
Fan
, “Analysis of biomolecule detection with optofluidic ring resonator sensors
,” Opt. Express
15
(15
), 9139
–9146
(2007
). 40.
L.
Fu
, Q.
Lu
, X.
Liu
, X.
Chen
, X.
Wu
, and S. J. T.
Xie
, “Combining whispering gallery mode optofluidic microbubble resonator sensor with GR-5 DNAzyme for ultra-sensitive lead ion detection
,” Talanta
213
, 120815
(2020
). 41.
H.
Wan
et al, “Label-free, ultra-low detection limit DNA biosensor using high quality optical microcavity functionalized by DNA tetrahedral nanostructure probes
,” Nanophotonics
12
(16
), 3323
–3331
(2023
). 42.
Z.
Wang
et al, “Ultra-sensitive DNAzyme-based optofluidic biosensor with liquid crystal-Au nanoparticle hybrid amplification for molecular detection
,” Sens. Actuators, B
359
, 131608
(2022
). 43.
S.
Geidel
et al, “Integration of an optical ring resonator biosensor into a self-contained microfluidic cartridge with active, single-shot micropumps
,” Micromachines
7
(9
), 153
(2016
). 44.
J.
Sun
et al, “Plasmon-coupled GaN microcavity for WGM lasing and label-free SERS sensing of biofluids
,” Adv. Opt. Mater.
12
(7
), 2301989
(2024
). 45.
A.
Ksendzov
and Y.
Lin
, “Integrated optics ring-resonator sensors for protein detection
,” Opt. Lett.
30
(24
), 3344
–3346
(2005
). 46.
Y.
Zhi
, X. C.
Yu
, Q.
Gong
, L.
Yang
, and Y. F.
Xiao
, “Single nanoparticle detection using optical microcavities
,” Adv. Mater.
29
(12
), 1604920
(2017
). 47.
J. T.
Gohring
, P. S.
Dale
, X. J. S.
Fan
, and A. B.
Chemical
, “Detection of HER2 breast cancer biomarker using the opto-fluidic ring resonator biosensor
,” Sens. Actuators, B
146
(1
), 226
–230
(2010
). 48.
V. R.
Dantham
, S.
Holler
, C.
Barbre
, D.
Keng
, V.
Kolchenko
, and S.
Arnold
, “Label-free detection of single protein using a nanoplasmonic-photonic hybrid microcavity
,” Nano Lett.
13
(7
), 3347
–3351
(2013
). 49.
Y.
Wu
, D. Y.
Zhang
, P.
Yin
, and F.
Vollmer
, “Ultraspecific and highly sensitive nucleic acid detection by integrating a DNA catalytic network with a label-free microcavity
,” Small
10
(10
), 2067
–2076
(2014
). 50.
M. D.
Baaske
, M. R.
Foreman
, and F.
Vollmer
, “Single-molecule nucleic acid interactions monitored on a label-free microcavity biosensor platform
,” Nat. Nanotechnol.
9
(11
), 933
–939
(2014
). 51.
Z. Y. H.
Wang
, G. C.
Fang
, Z. H.
Gao
, Y. K.
Liao
, C. Y.
Gong
, M.
Kim
, G. E.
Chang
, S. L.
Feng
, T. H.
Xu
, T. G.
Liu
, and Y. C.
Chen
, “Autonomous microlasers for profiling extracellular vesicles from cancer spheroids
,” Nano Lett.
23
, 2502
–2510
(2023
). 52.
E. J.
Smith
, S.
Schulze
, S.
Kiravittaya
, Y.
Mei
, S.
Sanchez
, and O. G.
Schmidt
, “Lab-in-a-tube: Detection of individual mouse cells for analysis in flexible split-wall microtube resonator sensors
,” Nano Lett.
11
, 4037
–4042
(2011
). 53.
M.
Schubert
et al, “Monitoring contractility in cardiac tissue with cellular resolution using biointegrated microlasers
,” Nat. Photonics
14
(7
), 452
–458
(2020
). 54.
A. L.
Washburn
, M. S.
Luchansky
, A. L.
Bowman
, and R. C.
Bailey
, “Quantitative, label-free detection of five protein biomarkers using multiplexed arrays of silicon photonic microring resonators
,” Anal. Chem.
82
(1
), 69
–72
(2010
). 55.
E.
Nuhiji
and P.
Mulvaney
, “Detection of unlabeled oligonucleotide targets using whispering gallery modes in single, fluorescent microspheres
,” Small
3
(8
), 1408
–1414
(2007
). 56.
M. S.
Murib
et al, “Photonic detection and characterization of DNA using sapphire microspheres
,” J. Biomed. Opt.
19
(9
), 97006
(2014
). 57.
T.
Lu
, H.
Lee
, T.
Chen
, S.
Herchak
, J. H.
Kim
, S. E.
Fraser
, R. C.
Flagan
, and K.
Vahala
, “High sensitivity nanoparticle detection using optical microcavities
,” Proc. Natl. Acad. Sci. U.S.A.
108
(15
), 5976
–5979
(2011
). 58.
J.
Mandana
and E.
Daniel
, “Early stage, label-free detection of breast cancer based on exosome’s protein content alteration
,” Proc. SPIE
12139
, 121390G
(2022
). © 2024 Author(s). Published under an exclusive license by AIP Publishing.
2024
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