Manipulation of red blood cells (RBCs) in microscale has proven to play a pivotal role in various applications, such as disease diagnosis and drug delivery. Over the past decades, the capabilities of microscale manipulation techniques have evolved from simple particle manipulation to cells and organisms, with numerous microfluidic-based research tools being developed for RBC manipulation. This review first introduces the reported microscale manipulation techniques and their principles, including passive microfluidic methods based on microstructures and hydrodynamics, as well as active methods such as acoustic, optical, and electrical techniques. It then focuses on the application scenarios of these micro-scale manipulation methods for RBC manipulation, including the investigation of RBC mechanical properties, the preparation of RBC carriers, the control of RBC rotation, and RBC lysis. Finally, the future prospects of microscale techniques in RBC manipulation are discussed. This review offers a comprehensive comparison of various techniques, aiming to provide researchers from different fields with a broad perspective and to guide the continued development of microscale manipulation methods for RBC applications. It seeks to help researchers from diverse backgrounds stay informed about the latest trends and advancements in the field.

1.
J. M.
Kwan
,
Q.
Guo
,
D. L.
Kyluik-Price
,
H.
Ma
, and
M. D.
Scott
, “
Microfluidic analysis of cellular deformability of normal and oxidatively damaged red blood cells
,”
Am. J. Hematol.
88
(
8
),
682
689
(
2013
).
2.
K. T.
Navya
,
K.
Prasad
, and
B. M. K.
Singh
, “
Analysis of red blood cells from peripheral blood smear images for anemia detection: A methodological review
,”
Med. Biol. Eng. Comput.
60
(
9
),
2445
2462
(
2022
).
3.
S.
Yadav
,
Deepika
, and
P. K.
Maurya
, “
A systematic review of red blood cells biomarkers in human aging
,”
J. Gerontol. Ser. A: Biol. Sci. Med. Sci.
79
(
4
),
glae004
(
2024
).
4.
J.
Dybas
,
F. C.
Alcicek
,
A.
Wajda
,
M.
Kaczmarska
,
A.
Zimna
,
K.
Bulat
,
A.
Blat
,
T.
Stepanenko
,
T.
Mohaissen
,
E.
Szczesny-Malysiak
,
D.
Perez-Guaita
,
B. R.
Wood
, and
K. M.
Marzec
, “
Trends in biomedical analysis of red blood cells—Raman spectroscopy against other spectroscopic, microscopic and classical techniques
,”
TrAC Trends Anal. Chem.
146
,
116481
(
2022
).
5.
N. M.
Ralbovsky
and
I. K.
Lednev
, “
Analysis of individual red blood cells for celiac disease diagnosis
,”
Talanta
221
,
121642
(
2021
).
6.
E. I.
Obeagu
, “
Red blood cells as biomarkers and mediators in complications of diabetes mellitus: A review
,”
Medicine
103
(
8
),
E37265
(
2024
).
7.
B. E.
Barber
,
B.
Russell
,
M. J.
Grigg
,
R.
Zhang
,
T.
William
,
A.
Amir
,
Y. L.
Lau
,
M. D.
Chatfield
,
A. M.
Dondorp
,
N. M.
Anstey
, and
T. W.
Yeo
, “
Reduced red blood cell deformability in Plasmodium knowlesi malaria
,”
Blood Adv.
2
(
4
),
433
443
(
2018
).
8.
C. H.
Villa
,
A. C.
Anselmo
,
S.
Mitragotri
, and
V.
Muzykantov
, “
Red blood cells: Supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems
,”
Adv. Drug Deliv. Rev.
106
,
88
103
(
2016
).
9.
J.
Yan
,
J.
Yu
,
C.
Wang
, and
Z.
Gu
, “
Red blood cells for drug delivery
,”
Small Methods
1
(
12
),
1700270
(
2017
).
10.
M.
Chen
,
Y.
Leng
,
C.
He
,
X.
Li
,
L.
Zhao
,
Y.
Qu
, and
Y.
Wu
, “
Red blood cells: A potential delivery system
,”
J. Nanobiotechnol.
21
,
288
(
2023
).
11.
K. E.
Bremmell
,
A.
Evans
, and
C. A.
Prestidge
, “
Deformation and nano-rheology of red blood cells: An AFM investigation
,”
Colloids Surf. B
50
(
1
),
43
48
(
2006
).
12.
J. L.
Maciaszek
and
G.
Lykotrafitis
, “
Sickle cell trait human erythrocytes are significantly stiffer than normal
,”
J. Biomech.
44
(
4
),
657
661
(
2011
).
13.
S.
Barns
,
M. A.
Balanant
,
E.
Sauret
,
R.
Flower
,
S.
Saha
, and
Y. T.
Gu
, “
Investigation of red blood cell mechanical properties using AFM indentation and coarse-grained particle method
,”
Biomed. Eng. Online
16
(
1
),
140
(
2017
).
14.
F.
Thom
, “
Mechanical properties of the human red blood cell membrane at −15 °C
,”
Cryobiology
59
(
1
),
24
27
(
2009
).
15.
A. W. L.
Jay
, “
Viscoelastic properties of the human red blood cell membrane
,”
Biophys. J.
13
(
11
),
1166
1182
(
1973
).
16.
H.
Pu
,
N.
Liu
,
J.
Yu
,
Y.
Yang
,
Y.
Sun
,
Y.
Peng
,
S.
Xie
,
J.
Luo
,
L.
Dong
,
H.
Chen
, and
Y.
Sun
, “
Micropipette aspiration of single cells for both mechanical and electrical characterization
,”
IEEE Trans. Biomed. Eng.
66
(
11
),
3185
3191
(
2019
).
17.
M.
Cauchi
,
I.
Grech
,
B.
Mallia
,
P.
Mollicone
, and
N.
Sammut
, “
Analytical, numerical and experimental study of a horizontal electrothermal MEMS microgripper for the deformability characterisation of human red blood cells
,”
Micromachines
9
(
3
),
108
(
2018
).
18.
Y.
Li
,
F.
Raza
,
Y.
Liu
,
Y.
Wei
,
R.
Rong
,
M.
Zheng
,
W.
Yuan
,
J.
Su
,
M.
Qiu
,
Y.
Li
,
F.
Raza
,
Y.
Liu
,
Y.
Wei
,
R.
Rong
,
M.
Zheng
,
W.
Yuan
,
J.
Su
, and
M.
Qiu
, “
Clinical progress and advanced research of red blood cells based drug delivery system
,”
Biomaterials
279
,
121202
(
2021
).
19.
G.
Della Pelle
and
N.
Kostevšek
, “
Nucleic acid delivery with red-blood-cell-based carriers
,”
Int. J. Mol. Sci.
22
(
10
),
5264
(
2021
).
20.
Z.
Wu
,
T.
Li
,
J.
Li
,
W.
Gao
,
T.
Xu
,
C.
Christianson
,
W.
Gao
,
M.
Galarnyk
,
Q.
He
,
L.
Zhang
, and
J.
Wang
, “
Turning erythrocytes into functional micromotors
,”
ACS Nano
8
(
12
),
12041
12048
(
2014
).
21.
A.
Antonelli
,
C.
Sfara
,
E.
Manuali
,
I. J.
Bruce
, and
M.
Magnani
, “
Encapsulation of superparamagnetic nanoparticles into red blood cells as new carriers of MRI contrast agents
,”
Nanomedicine
6
(
2
),
211
223
(
2011
).
22.
A.
Jiang
,
B.
Song
,
X.
Ji
,
F.
Peng
,
H.
Wang
,
Y.
Su
, and
Y.
He
, “
Doxorubicin-loaded silicon nanoparticles impregnated into red blood cells featuring bright fluorescence, strong photostability, and lengthened blood residency
,”
Nano Res.
11
(
4
),
2285
2294
(
2018
).
23.
A.
Antonelli
,
C.
Sfara
,
J.
Rahmer
,
B.
Gleich
,
J.
Borgert
, and
M.
Magnani
, “
Red blood cells as carriers in magnetic particle imaging
,”
Biomed. Tech.
58
(
6
),
517
525
(
2013
).
24.
Z.
Wu
,
B.
Esteban-Fernández de Ávila
,
A.
Martín
,
C.
Christianson
,
W.
Gao
,
S. K.
Thamphiwatana
,
A.
Escarpa
,
Q.
He
,
L.
Zhang
, and
J.
Wang
, “
RBC micromotors carrying multiple cargos towards potential theranostic applications
,”
Nanoscale
7
(
32
),
13680
13686
(
2015
).
25.
M.
Robert
,
B.
Laperrousaz
,
D.
Piedrahita
,
E. F.
Gautier
,
T.
Nemkov
,
F.
Dupuy
,
E.
Nader
,
V.
Salnot
,
P.
Mayeux
,
A.
D’Alessandro
,
C.
Lavazec
,
P.
Joly
,
A.
Scheer
,
P.
Connes
, and
A.
Cibiel
, “
Multiparametric characterization of red blood cell physiology after hypotonic dialysis based drug encapsulation process
,”
Acta Pharm. Sin. B
12
(
4
),
2089
2102
(
2022
).
26.
E.
Xu
,
X.
Wu
,
X.
Zhang
,
K.
Zul
,
F.
Raza
,
J.
Su
, and
M.
Qiu
, “
Study on the protection of dextran on erythrocytes during drug loading
,”
Colloids Surf. B
189
,
110882
(
2020
).
27.
L.
He
,
M.
Shao
,
X.
Yang
,
L.
Si
,
M.
Jiang
,
T.
Wang
,
Z.
Ke
,
T.
Peng
,
S.
Fang
,
S.
Zhang
,
X.
Ouyang
,
G.
Zhao
, and
J.
Zhou
, “
Morphology analysis of unlabeled red blood cells based on quantitative differential phase contrast microscopy
,”
Cytometry, Part A
101
(
8
),
648
657
(
2022
).
28.
I.
Moon
,
F.
Yi
,
Y. H.
Lee
,
B.
Javidi
,
D.
Boss
, and
P.
Marquet
, “
Automated quantitative analysis of 3D morphology and mean corpuscular hemoglobin in human red blood cells stored in different periods
,”
Opt. Express
21
(
25
),
30947
(
2013
).
29.
K.
Jaferzadeh
,
M. W.
Sim
,
N. G.
Kim
, and
I. K.
Moon
, “
Quantitative analysis of three-dimensional morphology and membrane dynamics of red blood cells during temperature elevation
,”
Sci. Rep.
9
,
14062
(
2019
).
30.
L.
Rey-Barroso
,
M.
Roldán
,
F. J.
Burgos-Fernández
,
I.
Isola
,
A.
Ruiz Llobet
,
S.
Gassiot
,
E.
Sarrate
, and
M.
Vilaseca
, “
Membrane protein detection and morphological analysis of red blood cells in hereditary spherocytosis by confocal laser scanning microscopy
,”
Microsc. Microanal.
29
(
2
),
777
785
(
2023
).
31.
S. H.
Li
,
X.
Liao
,
T. E.
Zhou
,
L. L.
Xiao
,
Y. W.
Chen
,
F.
Wu
,
J. R.
Wang
,
B.
Cheng
,
J. X.
Song
, and
H. W.
Liu
, “
Evaluation of 2 purification methods for isolation of human adipose-derived stem cells based on red blood cell lysis with ammonium chloride and hypotonic sodium chloride solution
,”
Ann. Plast. Surg.
78
(
1
),
83
90
(
2017
).
32.
H.
Germain
,
S.
Tarfi
,
N.
Freynet
,
A.
Toma
,
B.
Badaoui
, and
O.
Wagner Ballon
, “
Red blood cell lysis procedure improves the performances of ELN dyserythropoiesis score compared to nuclear dye use without lysis
,”
Blood
132
(
Supplement 1
),
3108
(
2018
).
33.
W. M.
Zhou
,
Y. Y.
Yan
,
Q. R.
Guo
,
H.
Ji
,
H.
Wang
,
T. T.
Xu
,
B.
Makabel
,
C.
Pilarsky
,
G.
He
,
X. Y.
Yu
, and
J. Y.
Zhang
, “
Microfluidics applications for high-throughput single cell sequencing
,”
J. Nanobiotechnol.
19
,
312
(
2021
).
34.
N.
Sinha
,
N.
Subedi
, and
J.
Tel
, “
Integrating immunology and microfluidics for single immune cell analysis
,”
Front. Immunol.
9
,
2373
(
2018
).
35.
S.
Lin
,
D.
Feng
,
X.
Han
,
L.
Li
,
Y.
Lin
, and
H.
Gao
, “
Microfluidic platform for omics analysis on single cells with diverse morphology and size: A review
,”
Anal. Chim. Acta
1294
,
342217
(
2024
).
36.
S.
Shukhratovich Abdullaev
,
R. H.
Althomali
,
A.
Raza Khan
,
H.
Sanaan Jabbar
,
M.
Abosoda
,
A.
Ihsan
,
S.
Aggarwal
,
Y. F.
Mustafa
,
I.
Hammoud Khlewee
, and
A.
Mhussan Jabbar
, “
Integrating of analytical techniques with enzyme-mimicking nanomaterials for the fabrication of microfluidic systems for biomedical analysis
,”
Talanta
273
,
125896
(
2024
).
37.
Z. C.
Ma
,
J.
Fan
,
H.
Wang
,
W.
Chen
,
G. Z.
Yang
, and
B.
Han
, “
Microfluidic approaches for microactuators: From fabrication, actuation, to functionalization
,”
Small
19
(
22
),
2300469
(
2023
).
38.
S.
Aralekallu
,
R.
Boddula
, and
V.
Singh
, “
Development of glass-based microfluidic devices: A review on its fabrication and biologic applications
,”
Mater. Des.
225
,
111517
(
2023
).
39.
W.
Li
,
Z.
Yao
,
T.
Ma
,
Z.
Ye
,
K.
He
,
L.
Wang
,
H.
Wang
,
Y.
Fu
, and
X.
Xu
, “
Acoustofluidic precise manipulation: Recent advances in applications for micro/nano bioparticles
,”
Adv. Colloid Interface Sci.
332
,
103276
(
2024
).
40.
Y.
Zheng
,
J.
Nguyen
,
Y.
Wei
, and
Y.
Sun
, “
Recent advances in microfluidic techniques for single-cell biophysical characterization
,”
Lab Chip
13
(
13
),
2464
2483
(
2013
).
41.
K.
Matthews
,
E. S.
Lamoureux
,
M. E.
Myrand-Lapierre
,
S. P.
Duffy
, and
H.
Ma
, “
Technologies for measuring red blood cell deformability
,”
Lab Chip
22
(
7
),
1254
1274
(
2022
).
42.
Y.
Kikuchi
,
T.
Arai
, and
T.
Koyama
, “
Improved filtration method for red cell deformability measurement
,”
Med. Biol. Eng. Comput.
21
(
3
),
270
276
(
1983
).
43.
S. C.
Gifford
,
M. G.
Frank
,
J.
Derganc
,
C.
Gabel
,
R. H.
Austin
,
T.
Yoshida
, and
M. W.
Bitensky
, “
Parallel microchannel-based measurements of individual erythrocyte areas and volumes
,”
Biophys. J.
84
(
1
),
623
633
(
2003
).
44.
D. S.
Ali
,
S. O.
Sofela
,
M.
Deliorman
,
P.
Sukumar
,
M. S.
Abdulhamid
,
S.
Yakubu
,
C.
Rooney
,
R.
Garrod
,
A.
Menachery
,
R.
Hijazi
,
H.
Saadi
, and
M. A.
Qasaimeh
, “
OMEF biochip for evaluating red blood cell deformability using dielectrophoresis as a diagnostic tool for type 2 diabetes mellitus
,”
Lab Chip
24
(
11
),
2906
2919
(
2024
).
45.
Z.
Ma
,
J.
Xia
,
N.
Upreti
,
E.
David
,
J.
Rufo
,
Y.
Gu
,
K.
Yang
,
S.
Yang
,
X.
Xu
,
J.
Kwun
,
E.
Chambers
, and
T. J.
Huang
, “
An acoustofluidic device for the automated separation of platelet-reduced plasma from whole blood
,”
Microsystems Nanoeng.
10
,
83
(
2024
).
46.
B.
Cha
,
S. H.
Lee
,
S. A.
Iqrar
,
H. G.
Yi
,
J.
Kim
, and
J.
Park
, “
Rapid acoustofluidic mixing by ultrasonic surface acoustic wave-induced acoustic streaming flow
,”
Ultrason. Sonochem.
99
,
106575
(
2023
).
47.
I. A.
Favre-Bulle
and
E. K.
Scott
, “
Optical tweezers across scales in cell biology
,”
Trends Cell Biol.
32
(
11
),
932
946
(
2022
).
48.
I.
Doh
,
W. C.
Lee
,
Y.-H.
Cho
,
A. P.
Pisano
, and
F. A.
Kuypers
, “
Deformation measurement of individual cells in large populations using a single-cell microchamber array chip
,”
Appl. Phys. Lett.
100
(
17
),
173702
(
2012
).
49.
A.
Saadat
,
D. A.
Huyke
,
D. I.
Oyarzun
,
P. V.
Escobar
,
I. H.
Øvreeide
,
E. S. G.
Shaqfeh
, and
J. G.
Santiago
, “
A system for the high-throughput measurement of the shear modulus distribution of human red blood cells
,”
Lab Chip
20
(
16
),
2927
2936
(
2020
).
50.
P.
Mishra
,
M.
Hill
, and
P.
Glynne-Jones
, “
Deformation of red blood cells using acoustic radiation forces
,”
Biomicrofluidics
8
(
3
),
034109
(
2014
).
51.
D. W.
Lee
and
Y.-H.
Cho
, “
A continuous electrical cell lysis device using a low dc voltage for a cell transport and rupture
,”
Sens. Actuators B
124
(
1
),
84
89
(
2007
).
52.
S.
Sakuma
,
K.
Kuroda
,
C. H. D.
Tsai
,
W.
Fukui
,
F.
Arai
, and
M.
Kaneko
, “
Red blood cell fatigue evaluation based on the close-encountering point between extensibility and recoverability
,”
Lab Chip
14
(
6
),
1135
1141
(
2014
).
53.
R.
Reale
,
A.
De Ninno
,
T.
Nepi
,
P.
Bisegna
, and
F.
Caselli
, “
Extensional-flow impedance cytometer for contactless and optics-free erythrocyte deformability analysis
,”
IEEE Trans. Biomed. Eng.
70
(
2
),
565
572
(
2023
).
54.
J.
Kim
,
M.
Johnson
,
P.
Hill
, and
B. K.
Gale
, “
Microfluidic sample preparation: Cell lysis and nucleic acid purification
,”
Integr. Biol.
1
(
10
),
574
586
(
2009
).
55.
M. E.
Myrand-Lapierre
,
X.
Deng
,
R. R.
Ang
,
K.
Matthews
,
A. T.
Santoso
, and
H.
Ma
, “
Multiplexed fluidic plunger mechanism for the measurement of red blood cell deformability
,”
Lab Chip
15
(
1
),
159
167
(
2015
).
56.
X.
Guo
,
M.
Sun
,
Y.
Yang
,
H.
Xu
,
J.
Liu
,
S.
He
,
Y.
Wang
,
L.
Xu
,
W.
Pang
, and
X.
Duan
, “
Controllable cell deformation using acoustic streaming for membrane permeability modulation
,”
Adv. Sci.
8
(
3
),
2002489
(
2021
).
57.
W. G.
Lee
,
H.
Bang
,
H.
Yun
,
J.
Lee
,
J.
Park
,
J. K.
Kim
,
S.
Chung
,
K.
Cho
,
C.
Chung
,
D. C.
Han
, and
J. K.
Chang
, “
On-chip erythrocyte deformability test under optical pressure
,”
Lab Chip
7
(
4
),
516
519
(
2007
).
58.
A.
Pourabed
,
T.
Chakkumpulakkal Puthan Veettil
,
C.
Devendran
,
P.
Nair
,
B. R.
Wood
, and
T.
Alan
, “
A star shaped acoustofluidic mixer enhances rapid malaria diagnostics via cell lysis and whole blood homogenisation in 2 seconds
,”
Lab Chip
22
(
9
),
1829
1840
(
2022
).
59.
Q.
Guo
,
S. P.
Duffy
,
K.
Matthews
,
A. T.
Santoso
,
M. D.
Scott
, and
H.
Ma
, “
Microfluidic analysis of red blood cell deformability
,”
J. Biomech.
47
(
8
),
1767
1776
(
2014
).
60.
H.
Bow
,
I. V.
Pivkin
,
M.
Diez-Silva
,
S. J.
Goldfless
,
M.
Dao
,
J. C.
Niles
,
S.
Suresh
, and
J.
Han
, “
A microfabricated deformability-based flow cytometer with application to malaria
,”
Lab Chip
11
(
6
),
1065
1073
(
2011
).
61.
S. S.
Lee
,
Y.
Yim
,
K. H.
Ahn
, and
S. J.
Lee
, “
Extensional flow-based assessment of red blood cell deformability using hyperbolic converging microchannel
,”
Biomed. Microdevices
11
(
5
),
1021
1027
(
2009
).
62.
Z.
Xu
,
Y.
Zheng
,
X.
Wang
,
N.
Shehata
,
C.
Wang
, and
Y.
Sun
, “
Stiffness increase of red blood cells during storage
,”
Microsyst. Nanoeng.
4
(
1
),
1
(
2018
).
63.
V.
Faustino
,
D.
Pinho
,
S. O.
Catarino
,
G.
Minas
, and
R. A.
Lima
, “
Geometry effect in multi-step crossflow microfluidic devices for red blood cells separation and deformability assessment
,”
Biomed. Microdevices
24
(
2
),
20
(
2022
).
64.
H.
Noguchi
and
G.
Gompper
, “
Shape transitions of fluid vesicles and red blood cells in capillary flows
,”
Proc. Natl. Acad. Sci. U.S.A.
102
(
40
),
14159
14164
(
2005
).
65.
J.
Rufo
,
F.
Cai
,
J.
Friend
,
M.
Wiklund
, and
T. J.
Huang
, “
Acoustofluidics for biomedical applications
,”
Nat. Rev. Methods Prim.
2
(
1
),
30
(
2022
).
66.
A.
Ozcelik
,
J.
Rufo
,
F.
Guo
,
Y.
Gu
,
P.
Li
,
J.
Lata
, and
T. J.
Huang
, “
Acoustic tweezers for the life sciences
,”
Nat. Methods
15
(
12
),
1021
1028
(
2018
).
67.
M. B.
Dentry
,
L. Y.
Yeo
, and
J. R.
Friend
, “
Frequency effects on the scale and behavior of acoustic streaming
,”
Phys. Rev. E
89
(
1
),
013203
(
2014
).
68.
Y.
Liu
,
Q.
Yin
,
Y.
Luo
,
Z.
Huang
,
Q.
Cheng
,
W.
Zhang
,
B.
Zhou
,
Y.
Zhou
, and
Z.
Ma
, “
Manipulation with sound and vibration: A review on the micromanipulation system based on sub-MHz acoustic waves
,”
Ultrason. Sonochem.
96
,
106441
(
2023
).
69.
W.
Zhang
,
B.
Song
,
X.
Bai
,
L.
Jia
,
L.
Song
,
J.
Guo
, and
L.
Feng
, “
Versatile acoustic manipulation of micro-objects using mode-switchable oscillating bubbles: Transportation, trapping, rotation, and revolution
,”
Lab Chip
21
(
24
),
4760
4771
(
2021
).
70.
Q.
Tang
,
F.
Liang
,
L.
Huang
,
P.
Zhao
, and
W.
Wang
, “
On-chip simultaneous rotation of large-scale cells by acoustically oscillating bubble array
,”
Biomed. Microdevices
22
(
1
),
13
(
2020
).
71.
P. H.
Huang
,
S.
Zhao
,
H.
Bachman
,
N.
Nama
,
Z.
Li
,
C.
Chen
,
S.
Yang
,
M.
Wu
,
S. P.
Zhang
, and
T. J.
Huang
, “
Acoustofluidic synthesis of particulate nanomaterials
,”
Adv. Sci.
6
(
19
),
1900913
(
2019
).
72.
N.
Hao
,
P.
Liu
,
H.
Bachman
,
Z.
Pei
,
P.
Zhang
,
J.
Rufo
,
Z.
Wang
,
S.
Zhao
, and
T. J.
Huang
, “
Acoustofluidics-assisted engineering of multifunctional three-dimensional zinc oxide nanoarrays
,”
ACS Nano
14
(
5
),
6150
6163
(
2020
).
73.
R.
You
,
Q.
Fan
,
Z.
Wang
,
W.
Xing
,
Y.
Wang
,
Y.
Song
,
X.
Duan
,
R.
You
, and
Y.
Wang
,“
A miniaturized wireless micropump enabled by confined acoustic streaming,”
Research
7
,
0314
(
2024
).
74.
J.
Liu
,
X.
Guo
,
M.
Sun
,
H.
Xu
,
W.
Pang
, and
X.
Duan
, “
Transdermal drug delivery based on liquid needles generated by hypersonic systems
,” in
Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems
(IEEE,
2020)
, pp.
408
411
.
75.
C.
Bustamante
,
C.
Bustamante
,
L.
Alexander
,
K.
MacIuba
, and
C. M.
Kaiser
, “
Single-molecule studies of protein folding with optical tweezers
,”
Annu. Rev. Biochem.
89
,
443
470
(
2020
).
76.
D.
Gao
,
W.
Ding
,
M.
Nieto-Vesperinas
,
X.
Ding
,
M.
Rahman
,
T.
Zhang
,
C. T.
Lim
, and
C. W.
Qiu
, “
Optical manipulation from the microscale to the nanoscale: Fundamentals, advances and prospects
,”
Light: Sci. Appl.
6
,
e17039
(
2017
).
77.
A.
Ashkin
,
J. M.
Dziedzic
,
J. E.
Bjorkholm
, and
S.
Chu
, “
Observation of a single-beam gradient force optical trap for dielectric particles
,”
Opt. Angular Momentum
11
(
5
),
288
290
(
1986
).
78.
J.
Yao
,
K.
Zhao
,
J.
Lou
, and
K.
Zhang
, “
Recent advances in dielectrophoretic manipulation and separation of microparticles and biological cells
,”
Biosensors
14
(
9
),
417
(
2024
).
79.
X. H.
Huang
,
K.
Torres-Castro
,
W.
Varhue
,
A.
Salahi
,
A.
Rasin
,
C.
Honrado
,
A.
Brown
,
J.
Guler
, and
N. S.
Swami
, “
Self-aligned sequential lateral field non-uniformities over channel depth for high throughput dielectrophoretic cell deflection
,”
Lab Chip
21
(
5
),
835
843
(2021).
80.
Y.
Qiang
,
J.
Liu
,
M.
Dao
,
S.
Suresh
, and
E.
Du
, “
Mechanical fatigue of human red blood cells
,”
Proc. Natl. Acad. Sci. U.S.A.
116
(
40
),
19828
19834
(
2019
).
81.
E.
Islamzada
,
K.
Matthews
,
Q.
Guo
,
A. T.
Santoso
,
S. P.
Duffy
,
M. D.
Scott
, and
H.
Ma
, “
Deformability based sorting of stored red blood cells reveals donor-dependent aging curves
,”
Lab Chip
20
(
2
),
226
235
(
2020
).
82.
Y.
Zheng
,
E.
Shojaei-Baghini
,
A.
Azad
,
C.
Wang
, and
Y.
Sun
, “
High-throughput biophysical measurement of human red blood cells
,”
Lab Chip
12
(
14
),
2560
2567
(
2012
).
83.
M. A.
Lizarralde Iragorri
,
S.
El Hoss
,
V.
Brousse
,
S. D.
Lefevre
,
M.
Dussiot
,
T.
Xu
,
A. R.
Ferreira
,
Y.
Lamarre
,
A. C.
Silva Pinto
,
S.
Kashima
,
C.
Lapouméroulie
,
D. T.
Covas
,
C.
Le Van Kim
,
Y.
Colin
,
J.
Elion
,
O.
Français
,
B.
Le Pioufle
, and
W.
El Nemer
, “
A microfluidic approach to study the effect of mechanical stress on erythrocytes in sickle cell disease
,”
Lab Chip
18
(
19
),
2975
2984
(
2018
).
84.
J. E.
Mancuso
and
W. D.
Ristenpart
, “
Stretching of red blood cells at high strain rates
,”
Phys. Rev. Fluids
2
(
10
),
101101
(
2017
).
85.
V.
Faustino
,
R. O.
Rodrigues
,
D.
Pinho
,
E.
Costa
,
A.
Santos-Silva
,
V.
Miranda
,
J. S.
Amaral
, and
R.
Lima
, “
A microfluidic deformability assessment of pathological red blood cells flowing in a hyperbolic converging microchannel
,”
Micromachines
10
(
10
),
645
(
2019
).
86.
M. H.
Rahman
,
C. H. N.
Wong
,
M. M.
Lee
,
M. K.
Chan
, and
Y. P.
Ho
, “
Efficient encapsulation of functional proteins into erythrocytes by controlled shear-mediated membrane deformation
,”
Lab Chip
21
(
11
),
2121
2128
(
2021
).
87.
V.
Rizzuto
,
A.
Mencattini
,
B.
Álvarez-González
,
D.
Di Giuseppe
,
E.
Martinelli
,
D.
Beneitez-Pastor
,
M. D.
Mañú-Pereira
,
M. J.
Lopez-Martinez
, and
J.
Samitier
, “
Combining microfluidics with machine learning algorithms for RBC classification in rare hereditary hemolytic anemia
,”
Sci. Rep.
11
(
1
),
13553
(
2021
).
88.
M. E.
Fay
,
O.
Oshinowo
,
E.
Iffrig
,
K. S.
Fibben
,
C.
Caruso
,
S.
Hansen
,
J. O.
Musick
,
J. M.
Valdez
,
S. S.
Azer
,
R. G.
Mannino
,
H.
Choi
,
D. Y.
Zhang
,
E. K.
Williams
,
E. N.
Evans
,
C. K.
Kanne
,
M. L.
Kemp
,
V. A.
Sheehan
,
M. A.
Carden
,
C. M.
Bennett
,
D. K.
Wood
, and
W. A.
Lam
, “
iCLOTS: Open-source, artificial intelligence-enabled software for analyses of blood cells in microfluidic and microscopy-based assays
,”
Nat. Commun.
14
(
1
),
5022
(
2023
).
89.
A.
Link
,
I. L.
Pardo
,
B.
Porr
, and
T.
Franke
, “
AI based image analysis of red blood cells in oscillating microchannels
,”
RSC Adv.
13
(
41
),
28576
28582
(
2023
).
90.
N.
Praljak
,
S.
Iram
,
U.
Goreke
,
G.
Singh
,
A.
Hill
,
U. A.
Gurkan
, and
M.
Hinczewski
, “
Integrating deep learning with microfluidics for biophysical classification of sickle red blood cells adhered to laminin
,”
PLoS Comput. Biol.
17
(
11
),
e1008946
(
2021
).
91.
M.
Razizadeh
,
M.
Nikfar
,
R.
Paul
, and
Y.
Liu
, “
Coarse-grained modeling of pore dynamics on the Red blood cell membrane under large deformations
,”
Biophys. J.
119
(
3
),
471
482
(
2020
).
92.
S.
Sohrabi
and
Y.
Liu
, “
A cellular model of shear-induced hemolysis
,”
Artif. Organs
41
(
9
),
E80
E91
(
2017
).
93.
M.
Piergiovanni
,
G.
Casagrande
,
F.
Taverna
,
I.
Corridori
,
M.
Frigerio
,
E.
Bianchi
,
F.
Arienti
,
A.
Mazzocchi
,
G.
Dubini
, and
M. L.
Costantino
, “
Shear-induced encapsulation into red blood cells: A New microfluidic approach to drug delivery
,”
Ann. Biomed. Eng.
48
(
1
),
236
246
(
2020
).
94.
P.
Sethu
,
M.
Anahtar
,
L. L.
Moldawer
,
R. G.
Tompkins
, and
M.
Toner
, “
Continuous flow microfluidic device for rapid erythrocyte lysis
,”
Anal. Chem.
76
(
21
),
6247
6253
(
2004
).
95.
C. X.
Xu
and
X. F.
Yin
, “
Continuous cell introduction and rapid dynamic lysis for high-throughput single-cell analysis on microfluidic chips with hydrodynamic focusing
,”
J. Chromatogr. A
1218
(
5
),
726
732
(
2011
).
96.
A.
Link
and
T.
Franke
, “
Acoustic erythrocytometer for mechanically probing cell viscoelasticity
,”
Lab Chip
20
(
11
),
1991
1998
(
2020
).
97.
C. S.
Centner
,
E. M.
Murphy
,
M. C.
Priddy
,
J. T.
Moore
,
B. R.
Janis
,
M. A.
Menze
,
A. P.
Defilippis
, and
J. A.
Kopechek
, “
Ultrasound-induced molecular delivery to erythrocytes using a microfluidic system
,”
Biomicrofluidics
14
(
2
),
024114
(
2020
).
98.
H.
Xu
,
R.
You
,
H.
Zhang
,
W.
Wei
,
T.
Li
, and
X.
Duan
, “
One-step on-chip preparation of nanoparticle-conjugated red blood cell carriers
,”
Colloids Surf. B
246
,
114373
(
2025
).
99.
Y.
Liu
and
F.
Xin
, “
Nonlinear large deformation of a spherical red blood cell induced by ultrasonic standing wave
,”
Biomech. Model. Mechanobiol.
21
(
2
),
589
604
(
2022
).
100.
Y.
Liu
and
F.
Xin
, “
Characterization of red blood cell deformability induced by acoustic radiation force
,”
Microfluid. Nanofluidics
26
(
1
),
1
12
(
2022
).
101.
L.
Meng
,
X.
Liu
,
Y.
Wang
,
W.
Zhang
,
W.
Zhou
,
F.
Cai
,
F.
Li
,
J.
Wu
,
L.
Xu
,
L.
Niu
, and
H.
Zheng
, “
Sonoporation of cells by a parallel stable cavitation microbubble array
,”
Adv. Sci.
6
(
17
),
1900557
(
2019
).
102.
H.
Xu
,
Z.
Wang
,
W.
Wei
,
T.
Li
, and
X.
Duan
, “
Microfluidic confined acoustic streaming vortex for liposome synthesis
,”
Lab Chip
24
,
2802
2810
(
2024
).
103.
Y.
Lu
,
J.
Huskens
,
W.
Pang
, and
X.
Duan
, “
Hypersonic poration of supported lipid bilayers
,”
Mater. Chem. Front.
3
(
5
),
782
790
(
2019
).
104.
S.
He
,
W.
Pang
,
X.
Wu
,
Y.
Yang
,
W.
Li
,
H.
Qi
,
C.
Sun
,
X.
Duan
, and
Y.
Wang
, “
A targeted hydrodynamic gold nanorod delivery system based on gigahertz acoustic streaming
,”
Nanoscale
14
(
41
),
15281
15290
(
2022
).
105.
O.
Jakobsson
,
M.
Antfolk
, and
T.
Laurell
, “
Continuous flow two-dimensional acoustic orientation of nonspherical cells
,”
Anal. Chem.
86
(
12
),
6111
6114
(
2014
).
106.
B.
Ran
,
B.
Liu
,
C.
Chen
,
W.
Tong
,
J.
Shi
,
J.
Du
,
Z.
Yu
,
S.
Bai
,
H.
Chen
, and
Y.
Zhu
, “
Acoustic micromixing in a serpentine channel with sharp teeth for controllable nanomaterial synthesis
,”
Chem. Eng. J.
504
,
159094
(
2025
).
107.
X.
Zhao
,
H.
Chen
,
Y.
Xiao
,
J.
Zhang
,
S.
Watanabe
, and
N.
Hao
, “
Sharp-edge–driven spiral acoustic micromixers for functional nanoarray engineering
,”
Mater. Today Nano
22
,
100338
(
2023
).
108.
Z.
Liu
,
Y.
Lu
,
W.
Tan
, and
G.
Zhu
, “
Dual-drive acoustic micromixer for rapid nucleation and ultrafast growth of perovskite nanoparticles
,”
Lab Chip
25
,
7
15
(
2024
).
109.
A.
Ashkin
, “
Acceleration and trapping of particles by radiation pressure
,”
Phys. Rev. Lett.
24
(
4
),
156
159
(
1970
).
110.
S.
Hénon
,
G.
Lenormand
,
A.
Richert
, and
F.
Gallet
, “
A new determination of the shear modulus of the human erythrocyte membrane using optical tweezers
,”
Biophys. J.
76
(
2
),
1145
1151
(
1999
).
111.
M. T.
Inanc
,
I.
Demirkan
,
C.
Ceylan
,
A.
Ozkan
,
O.
Gundogdu
,
U.
Goreke
,
U. A.
Gurkan
, and
M. B.
Unlu
, “
Quantifying the influences of radiation therapy on deformability of human red blood cells by dual-beam optical tweezers
,”
RSC Adv.
11
(
26
),
15519
15527
(
2021
).
112.
Z.
Yao
,
C. C.
Kwan
, and
A. W.
Poon
, “
An optofluidic ‘tweeze-and-drag’ cell stretcher in a microfluidic channel
,”
Lab Chip
20
(
3
),
601
613
(
2020
).
113.
W.
Zhao
,
H.
Yu
,
Y.
Wen
,
H.
Luo
,
B.
Jia
,
X.
Wang
,
L.
Liu
, and
W. J.
Li
, “
Real-time red blood cell counting and osmolarity analysis using a photoacoustic-based microfluidic system
,”
Lab Chip
21
(
13
),
2586
2593
(
2021
).
114.
S. K.
Mohanty
,
A.
Uppal
, and
P. K.
Gupta
, “
Self-rotation of red blood cells in optical tweezers: Prospects for high throughput malaria diagnosis
,”
Biotechnol. Lett.
26
(
12
),
971
974
(
2004
).
115.
J. A.
Dharmadhikari
,
S.
Roy
,
A. K.
Dharmadhikari
,
S.
Sharma
, and
D.
Mathur
, “
Naturally occurring, optically driven, cellular rotor
,”
Appl. Phys. Lett.
85
(
24
),
6048
6050
(
2004
).
116.
S. M.
Mohi
,
H. L.
Saadon
, and
A. A.
Khalaf
, “
Single laser trapping for optical folding and rotation of red blood cells in sickle cell disease in response to hydroxyurea treatment
,”
Biochem. Biophys. Res. Commun.
554
,
222
228
(
2021
).
117.
X.
Chen
,
G.
Xiao
,
X.
Han
,
W.
Xiong
,
H.
Luo
, and
B.
Yao
, “
Observation of spin and orbital rotation of red blood cell in dual-beam fibre-optic trap with transverse offset
,”
J. Opt.
19
(
5
),
055612
(
2017
).
118.
X.
Liu
,
J.
Huang
,
Y.
Li
,
Y.
Zhang
, and
B.
Li
, “
Rotation and deformation of human red blood cells with light from tapered fiber probes
,”
Nanophotonics
6
(
1
),
309
316
(
2017
).
119.
C.
Lizano
,
S.
Sanz
,
J.
Luque
, and
M.
Pinilla
, “
In vitro study of alcohol dehydrogenase and acetaldehyde dehydrogenase encapsulated into human erythrocytes by an electroporation procedure
,”
Biochim. Biophys. Acta, Gen. Subj.
1425
(
2
),
328
336
(
1998
).
120.
Y.
Cao
,
J.
Yang
,
Z. Q.
Yin
,
H. Y.
Luo
,
M.
Yang
,
N.
Hu
,
J.
Yang
,
D. Q.
Huo
,
C. J.
Hou
,
Z. Z.
Jiang
,
R. Q.
Zhang
,
R.
Xu
, and
X. L.
Zheng
, “
Study of high-throughput cell electrofusion in a microelectrode-array chip
,”
Microfluid. Nanofluidics
5
(
5
),
669
675
(
2008
).
121.
Y. K.
Lee
and
P. G.
Deng
, “
Review of micro/nano technologies and theories for electroporation of biological cells
,”
Sci. China: Phys., Mech. Astron.
55
(
6
),
996
1003
(
2012
).
122.
X.
Guo
and
R.
Zhu
, “
Controllable in-situ cell electroporation with cell positioning and impedance monitoring using micro electrode array
,”
Sci. Rep.
6
,
31392
(
2016
).
123.
J. J.
Fischer
and
H.
Yabuki
, “
Preparation of red blood cells containing exogenous hemogloblin
,”
Artif. Cells. Blood Substit. Immobil. Biotechnol.
26
(
4
),
377
387
(
1998
).
124.
A.
Lucas
,
D.
Lam
, and
P.
Cabrales
, “
Doxorubicin-loaded red blood cells reduced cardiac toxicity and preserved anticancer activity
,”
Drug Delivery
26
(
1
),
433
442
(
2019
).
125.
K.
Kinosita
and
T. Y.
Tsong
, “
Survival of sucrose-loaded erythrocytes in the circulation
,”
Nature
272
(
5650
),
258
260
(
1978
).
126.
K.
Kinosita
and
T. Y.
Tsong
, “
Hemolysis of human erythrocytes by a transient electric field
,”
Proc. Natl. Acad. Sci. U.S.A.
74
(
5
),
1923
1927
(
1977
).
127.
N.
Bao
,
G. C.
Kodippili
,
K. M.
Giger
,
V. M.
Fowler
,
P. S.
Low
, and
C.
Lu
, “
Single-cell electrical lysis of erythrocytes detects deficiencies in the cytoskeletal protein network
,”
Lab Chip
11
(
18
),
3053
3056
(
2011
).
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