Small,
Journal Year:
2023,
Volume and Issue:
20(7)
Published: Oct. 3, 2023
Abstract
Previous
on‐chip
technologies
for
characterizing
the
cellular
mechanical
properties
often
suffer
from
a
low
throughput
and
limited
sensitivity.
Herein,
an
inertial
multi‐force
deformability
cytometry
(IMFDC)
is
developed
high‐throughput,
high‐accuracy,
high‐applicability
tumor
cell
mechanotyping.
Three
different
deformations,
including
shear
deformations
stretch
under
forces,
are
integrated
with
IMFDC.
The
3D
focusing
of
cells
enables
to
deform
by
identical
fluid
flow,
10
parameters,
such
as
area,
perimeter,
deformability,
roundness,
rectangle
obtained
in
three
deformations.
IMFDC
able
evaluate
that
sensitive
forces
on
single
chip,
demonstrating
high
applicability
analyzing
lines.
In
identifying
types,
exhibit
responses
sizes
deformability.
A
discrimination
accuracy
≈93%
both
MDA‐MB‐231
MCF‐10A
≈500
s
−1
can
be
achieved
using
multiple‐parameters‐based
machine
learning
model.
Finally,
metastatic
pleural
peritoneal
effusions
characterized,
enabling
practical
application
clinical
cancer
diagnosis.
Smart Medicine,
Journal Year:
2022,
Volume and Issue:
1(1)
Published: Dec. 1, 2022
Microfluidic
detection
methods
for
cell
deformability
cytometry
have
been
regarded
as
powerful
tools
single-cell
analysis
of
cellular
mechanical
phenotypes,
thus
having
widely
applied
in
the
fields
preparation,
separation,
clinical
diagnostics
and
so
on.
Featured
with
traits
like
easy
operations,
low
cost
high
throughput,
such
shown
great
potentials
on
investigating
physiological
state
pathological
changes
during
deformation.
Herein,
a
review
advancements
microfluidic-based
deformation
is
presented.
We
discuss
several
representative
their
frontiers
practical
applications.
Finally,
we
analyze
current
status
propose
remaining
challenges
future
perspectives
development
directions.
Small,
Journal Year:
2023,
Volume and Issue:
19(45)
Published: July 12, 2023
Abstract
Reflecting
various
physiological
states
and
phenotypes
of
single
cells,
intrinsic
biophysical
characteristics
(e.g.,
mechanical
electrical
properties)
are
reliable
important,
label‐free
biomarkers
for
characterizing
cells.
However,
single‐modal
or
properties
alone
not
specific
enough
to
characterize
cells
accurately,
it
has
been
long
challenging
couple
the
conventionally
image‐based
characterization
impedance‐based
characterization.
In
this
work,
spatial‐temporal
impedance
sensing
signal
leveraged,
an
multimodal
electrical‐mechanical
flow
cytometry
framework
on‐the‐fly
high‐dimensional
measurement
is
proposed,
that
is,
Young's
modulus
E
,
fluidity
β
radius
r
cytoplasm
conductivity
σ
i
membrane
capacitance
C
sm
With
characterization,
can
better
reveal
difference
in
cell
types,
demonstrated
by
experimental
results
with
three
types
cancer
(HepG2,
MCF‐7,
MDA‐MB‐468)
93.4%
classification
accuracy
pharmacological
perturbations
cytoskeleton
(fixed
Cytochalasin
B
treated
cells)
95.1%
accuracy.
It
envisioned
provides
a
new
perspective
accurate
single‐cell
Small Methods,
Journal Year:
2022,
Volume and Issue:
6(7)
Published: May 20, 2022
Mechanical
properties
of
single
cells
are
important
label-free
biomarkers
normally
measured
by
expensive
and
complex
imaging
systems.
To
unlock
this
limit
allow
mechanical
comparable
across
different
measurement
platforms,
camera-free
intrinsic
cytometry
(CFIMC)
is
proposed
for
on-the-fly
two
major
parameters,
that
is,
Young's
modulus
E
fluidity
β,
cells.
CFIMC
adopts
a
framework
couples
the
impedance
electrodes
with
constriction
channel
spatially,
so
signals
contain
dynamic
deformability
information
cell
squeezing
through
channel.
Deformation
thus
extracted
from
used
to
derive
parameters.
With
reasonably
high
throughput
(>500
min-1
),
can
successfully
reveal
difference
in
cancer
normal
(i.e.,
human
breast
lines
MCF-10A,
MCF-7,
MDA-MB-231),
living
fixed
cells,
pharmacological
perturbations
cytoskeleton.
It
further
found
1
µM
level
concentration
Cytochalasin
B
may
be
threshold
treated
induce
significant
cytoskeleton
effect
reflected
envisioned
provides
an
alternative
avenue
high-throughput
real-time
single-cell
analysis.
Analytical Chemistry,
Journal Year:
2023,
Volume and Issue:
95(6), P. 3468 - 3475
Published: Feb. 1, 2023
Circulating
tumor
cells
(CTCs)
have
emerged
as
promising
circulating
biomarkers
for
non-invasive
cancer
diagnosis
and
management.
Isolation
detection
of
CTCs
in
clinical
samples
are
challenging
due
to
the
extreme
rarity
high
heterogeneity
CTCs.
Here,
we
describe
a
poly(ethylene
oxide)
(PEO)
concentration
gradient-based
microfluidic
method
rapid,
label-free,
highly
efficient
isolation
directly
from
whole
blood
samples.
Stable
gradients
PEO
were
formed
within
microchannel
by
co-injecting
side
fluid
(blood
sample
spiked
with
0.025%
PEO)
center
(0.075%
solution).
The
competition
between
elastic
lift
force
inertial
enabled
size-based
separation
large
small
based
on
their
distinct
migration
patterns.
device
could
process
1
mL
30
min,
efficiency
>90%
an
enrichment
ratio
>700
cells.
isolated
enumerated
immunofluorescence
staining,
allowing
discrimination
breast
patients
healthy
donors
accuracy
84.2%.
provides
powerful
tool
label-free
wide
range
applications.
Materials Today Bio,
Journal Year:
2023,
Volume and Issue:
19, P. 100594 - 100594
Published: Feb. 28, 2023
Single-cell
encapsulation
in
droplets
has
become
a
powerful
tool
immunotherapy,
medicine
discovery,
and
single-cell
analysis,
thanks
to
its
capability
for
cell
confinement
picoliter
volumes.
However,
the
purity
throughput
of
are
limited
by
random
process,
which
resuts
majority
empty
multi-cells
droplets.
Herein
we
introduce
first
label-free
selectable
quantity
sorting
system
overcome
this
problem.
The
utilizes
simple
reliable
electrical
impedance
based
screening
(98.9%
accuracy)
integrated
with
biocompatible
acoustic
select
droplets,
achieving
90.3%
efficiency
up
200
Hz
throughput,
removing
(∼60%
rejection)
(∼90%
rejection).
We
demonstrate
use
droplet
improve
∼9-fold
compared
conventional
process.
Small Science,
Journal Year:
2024,
Volume and Issue:
4(4)
Published: Feb. 2, 2024
From
deciphering
infection
and
disease
mechanisms
to
identifying
novel
biomarkers
personalizing
treatments,
the
characteristics
of
individual
cells
can
provide
significant
insights
into
a
variety
biological
processes
facilitate
decision‐making
in
biomedical
environments.
Conventional
single‐cell
analysis
methods
are
limited
terms
cost,
contamination
risks,
sample
volumes,
times,
throughput,
sensitivity,
selectivity.
Although
microfluidic
approaches
have
been
suggested
as
low‐cost,
information‐rich,
high‐throughput
alternative
conventional
isolation
methods,
limitations
such
necessary
off‐chip
pre‐
post‐processing
well
systems
designed
for
workflows
restricted
their
applications.
In
this
review,
comprehensive
overview
recent
advances
integrated
microfluidics
on‐chip
three
prominent
application
domains
provided:
investigation
somatic
(particularly
cancer
immune
cells),
stem
cells,
microorganisms.
Also,
use
cell
separation
(e.g.,
dielectrophoresis)
unconventional
or
ways,
which
advance
integration
multiple
systems,
is
discussed.
Finally,
critical
discussion
related
current
how
they
could
be
overcome
provided.
Small Methods,
Journal Year:
2024,
Volume and Issue:
8(7)
Published: Jan. 11, 2024
Abstract
The
existence
of
many
background
blood
cells
hinders
the
accurate
identification
circulating
tumor
(CTCs)
in
cancer
patients.
To
unlock
this
limitation,
a
hydrodynamic
sorting‐mechanotyping
cytometry
(HSMC)
integrated
with
sorting‐concentration
chip
and
detection
is
proposed
for
simultaneously
achieving
high‐throughput
cell
sorting
multi‐parameter
mechanotyping
sorted
cells.
HSMC
adopts
spiral
inertial
microfluidics
label‐free
manner,
allowing
efficient
enrichment
from
large
Then,
are
concentrated
by
concentration
unit
finally
passed
through
deformation.
has
high
throughput
can
successfully
reveal
differences
cellular
mechanical
properties.
After
characterizing
optimizing
single
chips,
white
(WBCs)
three
types
(A549,
MCF‐7,
MDA‐MB‐231
cells)
achieved.
accuracies
WBCs
different
all
larger
than
94%,
while
highest
accuracy
up
to
99.2%.
This
study
envisions
that
will
offer
an
avenue
analysis
intrinsic
mechanics
clinical
medicine.
Lab on a Chip,
Journal Year:
2021,
Volume and Issue:
21(15), P. 2869 - 2880
Published: Jan. 1, 2021
Submicron-precision
particle
characterization
is
crucial
for
counting,
sizing
and
identifying
a
variety
of
biological
particles,
such
as
bacteria
apoptotic
bodies.
Microfluidic
impedance
cytometry
has
been
attractive
in
current
research
microparticle
due
to
its
advantages
label-free
detection,
ease
miniaturization
affordability.
However,
conventional
electrode
configurations
three
electrodes
floating
have
not
yet
demonstrated
the
capability
probing
submicron
particles
or
microparticles
with
size
difference.
In
this
study,
we
present
high-throughput
(∼800
per
second)
impedance-based
microfluidic
flow
system
integrated
novel
design
double
differential
configuration,
enabling
detection
(down
0.4
μm)
minimum
resolution
200
nm.
The
signal-to-noise
ratio
boosted
from
13.98
dB
32.64
compared
typical
three-electrode
configuration.
With
proposed
cytometry,
shown
results
that
accurately
correlate
manufacturers'
datasheets
(R2
=
0.99938).
It
also
shows
population
ratios
differently
sized
beads
mixture
samples
are
consistent
given
by
commercial
fluorescence-based
(within
∼1%
difference).
This
work
provides
approach
precision
counting
microscale
new
avenue
designing
feature
suppressing
electrical
noise
accomplishing
high
wide
range
frequencies.
sensing
paves
pathway
real-time
analysis
accurate
screening
pathological
pharmacological
research.
