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Dimension-reconfigurable bubble film nanochannel for wetting based sensing

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Dimensions and surface properties are the predominant factors for the applications of nanofluidic devices. Here we use a thin liquid film as a nanochannel by inserting a gas bubble in a glass capillary, a technique we name bubble-based film nanofluidics. The height of the film nanochannel can be regulated by the Debye length and wettability, while the length independently changed by applied pressure. The film nanochannel behaves functionally identically to classical solid state nanochannels, as ion concentration polarizations. Furthermore, the film nanochannels can be used for label-free immunosensing, by principle of wettability change at the solid interface. The optimal sensitivity for the biotin-streptavidin reaction is two orders of magnitude higher than for the solid state nanochannel, suitable for a full range of electrolyte concentrations. We believe that the film nanochannel represents a class of nanofluidic devices that is of interest for fundamental studies and also can be widely applied, due to its reconfigurable dimensions, low cost, ease of fabrication and multiphase interfaces. Dimensions and the surface properties of the nanochannels are vital to the functions and applications of nano-fluidic devices. Here Ma et al. studied the film thickness of a Bretherton bubble in a microcapillary and demonstrate the liquid film can be used for label-free biosensing.
The tunable height and length of film nanochannel with characterizations a The measured conductance of film nanochannel per unit length at pH 8.5 (dots), with theoretical predictions (black solid line). The colored lines are theoretical conductance of a fictitious solid-state nanochannel with different surface charge densities and a height of 11 nm. b The calculated film thickness from the normalized conductance as a function of KCl concentration at pH 8.5 by theoretical approach (circle dots) and simulations by PNP equations (square dots). Dashed line shows the dependence of the Debye length on concentration. c The normalized conductance with 10 mM KCl solution. d The calculated film thickness as a function of pH at 10 mM solutions. Solid lines are the theoretical predictions described in Methods section. e Bubble shrinkage by applied pressure. The length of the film channel decreases with increasing external pressure of liquid phase. Snapshot of a single gas bubble when the applied external pressure increases from 0 to 1 bar. The length decreases to nearly half value when 1 bar pressure applied on the microchannel. f The decrease of bubble-length (upper graph, green squares)-induced decrease of film nanochannel resistance (upper graph, orange squares) as a function of applied pressure. Solid lines were derived from Eq. 1 with length predicted by Ideal Gas Law. The normalized resistance of film nanochannel (lower graph, dots) and channel height (lower graph, dots) remain constant due to the persistence of capillary pressure (contact angle of bubble). The error bars are the standard deviation of five or more individual results.
… 
Label-free immunosensing by film nanochannel a Schematic picture illustrating the principle of sensing the biotin-SAv reaction. b The functionalization with biotin (top) and subsequent successful binding of avidin on the capillary surface (bottom) was demonstrated by the fluorescence of FITC-SAv. c A change of contact angle in the capillary was observed after the immobilization of SAv. d The I–V curves show a strong change of the conductance induced by the biotin-SAv binding reaction (19 μM SAv). e The bubble length-normalized conductance of the film nanochannel Gfch* was derived by linear fitting in 10⁻³× to 10× PBS solutions. The dashed lines are the theoretical conductance of a ‘fictitious’ solid-state nanochannel neglecting the surface conductance. f Sensitivity (GSAv/Gbio) of film nanochannels (green) as function of salt concentration, compared to that of a polysilicon nanochannel¹³ (orange column). The blue square dots represent the contribution from the change of zeta potential, while the red circular dots represent the contribution from the wettability change. g The kinetics of the biotin-SAv reaction in 1 nM (orange square dots) and 10 nM (green circle dots) SAv solutions, with predicted ratio (0 to 1) of occupied biotin sites (right axis, solid lines). h The reaction kinetics in 50 nM (dark blue dots) and 200 nM (light blue dots) SAv solutions, with predicted ratio of biotin-SAv binding (right axis, solid lines). i The bubble-length normalized film nanochannel conductance Gfch* as a function of SAv concentration for 0.01× and 1× PBS solutions. The dashed lines represent the measured conductance before biotin-SAv binding at 0.01× (blue) and 1× (red) PBS, while the dots are measured Gfch* after SAv binding. j Calculated sensitivity as a function of SAv concentrations in 0.01× and 1× PBS solutions. The solid line represents data from a solid-state nanochannel⁵¹. The error bars are the standard deviation obtained from five or more individual measurements.
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ARTICLE
Dimension-recongurable bubble lm nanochannel
for wetting based sensing
Yu Ma1,2, Miao Sun1,2, Xuexin Duan 3, Albert van den Berg1,4, Jan C.T. Eijkel1,4 & Yanbo Xie1,2*
Dimensions and surface properties are the predominant factors for the applications of
nanouidic devices. Here we use a thin liquid lm as a nanochannel by inserting a gas bubble
in a glass capillary, a technique we name bubble-based lm nanouidics. The height of the
lm nanochannel can be regulated by the Debye length and wettability, while the length
independently changed by applied pressure. The lm nanochannel behaves functionally
identically to classical solid state nanochannels, as ion concentration polarizations. Further-
more, the lm nanochannels can be used for label-free immunosensing, by principle of
wettability change at the solid interface. The optimal sensitivity for the biotin-streptavidin
reaction is two orders of magnitude higher than for the solid state nanochannel, suitable for a
full range of electrolyte concentrations. We believe that the lm nanochannel represents a
class of nanouidic devices that is of interest for fundamental studies and also can be widely
applied, due to its recongurable dimensions, low cost, ease of fabrication and multiphase
interfaces.
https://doi.org/10.1038/s41467-020-14580-x OPEN
1International Joint Laboratory of Nanouidics and Interfaces, School of Physical Science and Technology, Northwestern Polytechnical University, 710100
Xian, China. 2MOE Key Laboratory of Material Physics and Chemistry under Extraordinary Conditions, School of Physical Science and Technology,
Northwestern Polytechnical University, 710072 Xian, China. 3State Key Laboratory of Precision Measuring Technology and Instruments, College of Precision
Instrument and Opto-Electronics Engineering, Tianjin University, 300072 Tianjin, China. 4BIOS Lab-on-a-Chip Group, MESA+Institute for Nanotechnology,
Technical Medical Centre and Max Planck Center for Complex Fluid Dynamics, University of Twente, 7522NB Enschede, The Netherlands.
*email: ybxie@nwpu.edu.cn
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The application of micro- and nanouidic devices has
greatly boosted the development of the chemical and bio-
logical sciences and technologies19. When the typical
length of a nanostructure approaches the thickness of the elec-
trical double layer (EDL), some unique phenomena occur that
have been widely used, for example for preconcentration10,
desalination11, bio-sensing12,13, and energy conversion14,15.
However, the technical barriers and cost of fabrication are con-
sidered to be constraints to the development of nanouidics16.
The invention of technologies helped to overcome these two
barriers1721. Besides, well-controlled dimensions and surfaces
are critical for the physicochemical properties of nanouidic
devices. Deformable nanochannels could for example help in
these respects, as the tunable dimension can be used for various
applications. Recently, Bonhomme et al., reported a soft nano-
uidic channel by using a foam bubble, which can produce a
circular deformable nanochannel with minimum height down to
50 nm, using liquid/air interfaces instead of liquid/solid inter-
faces22. These interfaces introduce some specic properties like
an electrical eld dependent thickness22, concentration-
independent conductance23, and an anomalous zeta potential24.
Inspired by the foam nanochannel22 and wetting lms at
surfaces25,26, here we report a lm nanouidic channel based on a
thin layer of liquid created by inserting a gas bubble in a glass
capillary. We name this technology bubble-based lm nano-
uidics (BFN). Although studies on liquid lms surrounding
bubbles in a capillary existed for decades2729, the lms were
rarely developed as a nanouidic device30, not speaking of a
detailed characterization of their properties. Bubble-based lm
nanouidic channels are fundamentally different from either
solid-state nanochannels or foam nanochannels since here three
(gas/liquid/solid) phases determine the properties instead of two
phases. Compared to the solid-state nanochannel, the height of
the lm nanochannel can be tuned by changing the EDL thick-
ness and wettability, with length of the lm nanochannel tuned
independently by applied pressure. Compared to the foam
nanochannel, the lm nanochannel can work in a surfactant-free
environment, which is more friendly to biological samples31.
Here we demonstrate that the BFN can exhibit functionalities
typical of solid state nanochannels, for instance ion concentration
polarization (ICP), useful for pre-concentration and desalination.
Besides, the lm nanochannel performs even better than the
solid-state nanochannel when used for label-free immunosensing,
based on the principle of wettability change. We coated biotin on
the capillary inner surface and demonstrated sensing of the
biotin-avidin reaction in the lm nanochannel. Our results
indicate that the optimal sensitivity in the lm nanochannel is
two orders of magnitude higher than in the solid-state nano-
channel, due to the change of wettability due to the reaction also
inuencing the lm nanochannel properties instead of only a
change in surface conduction as in the solid-state nanochannel.
Thus, the immunosensing capabilities of the lm nanochannel are
sustained over a full range of salt concentrations, where in the
solid-state nanochannel it only exists in low concentrated
solutions.
Results
Devices and principles. We generated bubbles of equal size with
a microuidic ow-focusing structure, created by a standard
PDMS chip fabrication and connection process (Fig. 1a)32.
Nitrogen gas (99.9% pure) ows in the center channel (100 μm
wide and 180 μm height), and was squeezed by the continuous
ow of electrolyte solutions on the branch channels forming
bubbles (Fig. 1b). The pressure of both the gas and water phases
was kept constant at 2050 mbar, operated by a pressure pump
(Fluigent, MF CF-EZ).
The bubbles were then conducted from a rectangular PDMS
channel to a circular capillary (Molex, 106815) of 100 μm inner
diameter. We kept a single slug bubble in the capillary by
stopping the ows, after which no apparent bubble shrinkage was
observed for at least 12 h. The bubble in the capillary occupies
most of the cross-sectional area of the glass capillary, leaving a
cylindrical liquid lm between solid and gas phase as shown in
Fig. 1a. The Laplace pressure in the bubble works against the
disjoining pressure in the liquid lm33. The balance of the two
pressures induces a speciclm thickness that is determined by
the EDL and the wettability of the solid surface. We characterized
the lm thickness by the electrical conductance using both Cyclic
Voltammetry (CV) and electrochemical impedance spectrum
(EIS) in a KCl solution, with two Ag/AgCl electrodes inserted at
pinched holes in the PDMS chip (Fig. 1e). The details of chip
fabrication and electrical characterizations are described in the
Methods section. The liquid/gas interface is molecularly smooth
due to the surface tension. Thus, the roughness of the capillary
inner surface is critical to the properties of the lm nanochannel.
We characterized the roughness of the glass capillary inner
surface by Atomic Force Microscope (Fig. 1f), and found an
average roughness of 2.6 nm with length-oriented wave-like
patterns, possibly originating from the capillary fabrication
process34.
To derive the resistance of the lm nanochannel, we used the
equivalent circuit shown in Fig. 1h, which consists of the
resistance of the microchannels including PDMS channels and
capillary (R
mch
), of the lm nanochannel (R
fch
) in case of a bubble
residing in the capillary, and the capacitance from the gas/liquid
interface at the bubble meniscus (C
b,cap
) and the EDL of the liquid
lm at the liquid/solid interface (C
fch
). The resistance from the
microchannels can be experimentally characterized and also
theoretically calculated when the dimensions and conductivity of
liquids are known. The presence of a single bubble in the capillary
signicantly increased the system resistance as shown in Fig. 1g.
This enabled us to derive the electrical resistance of the lm
nanochannel from the difference of resistance of the system with
and without a bubble, R
fch
=R
b,sys
R
nb,sys
. Here R
b,sys
and R
nb,sys
represent the resistance of system with bubble and without bubble
respectively. We could ignore the far smaller resistance of the
microcapillary compared with the same length of the bubble (See
Supplementary Note 1 for the calculations). The resistance
induced by the bubble meniscus (R
b,cap
) can also be ignored
compared to the lm nanochannel (R
fch
) in our experiments, as
we use a slug instead of a bubble (see Supplementary Note 2).
Electrical characterization. In our experiments, the typical
bubble-length ranged from 0.5 to 1.5 mm, with the remainder of
the microchannels lled with KCl solution. Figure 2a demon-
strates typical CV cycles measured in 10 mM KCl at pH =8.5 and
4. We found that the current amplitude gradually decreased and
became saturated after ~10 cycles, nally dropping off to 60% of
the rst cycle at pH =8.5. The decrease of conductance was more
obvious in the acidic solution (pH =4), with only 28% of con-
ductance remaining compared to the rst cycle. The reduction of
conductance was found at the beginning of every electrical
measurement after bubble generation, no matter how long we
kept the bubble before applying electrical elds. However, once
the conductance reached the saturated state, it remained constant.
More details can be seen in Supplementary Note 3. Typical IV
curves of the saturated states with solutions at pH 8.5 and 4
demonstrated an Ohmic response to the applied voltage shown in
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Fig. 2b. By linear tting the IVcurves (solid lines in Fig. 2b), we
can derive the time evolution of the system conductance (Fig. 2c).
We performed EIS to characterize the conductance as a
comparison to the conductance at the saturated states, as it avoids
ion concentration polarization and limiting-current effects12.We
found a similar conductance decrease in these EIS measurements,
decreasing faster with higher voltage amplitude (see Supplemen-
tary Note 4). We found that the value measured by EIS at
saturated state equaled the value measured by CV in the saturated
state (Fig. 2c). More details are shown in Supplementary Note 5.
We used the conductance values from EIS and the saturated states
of CV in the further analysis, unless noted otherwise.
When trying to explain the conductance changes in CV, we
noted that the surface of the liquid lmappearssmootherafter
40 CV cycles (800 s) than at the start of the electrical
measurement (see Inset of Fig. 2c). We hypothesize that
initially a small volume of water was trapped within the liquid
lm, causing a higher conductance of the system. Also,
contaminations could be trapped within the liquid lm. We
suspect that the reduction of conductance is due to the
extraction of this trapped water by the electrical elds. The
alternating electrical eld generates electroosmotic ow trans-
porting back and forth the trapped water and contaminants,
and nallyremovingthemfromtheliquidlm, inducing the
decrease of conductance. As reported, the side surface of a
moving bubble is slightly concave due to the shear stress of
uids in the channel35. More details of our hypothesis and
measurements can be found in the Supplementary Note 6.
abcd
e
f
g30 With bubble
Without bubble
Linear fitting
20
10
–10
–20
–30
–0.6 –0.3 0.0 0.3 0.6
V (V)
0
10
–10
1
0.5
00
0.5
1
0
I (nA)
h
Solution
Solution
Gas
200 μm
1 cm
200 μm100 μm
Microchannel
Capillary
Ag/AgCl
Rmch
Ground
V0
Cfch
Rb,cap Rfch
Cb,cap
Rb,cap
Rmch
Cb,cap
Bubble
x (μm)
y (μm)
z (nm)
Fig. 1 The principle of lm nanochannel and setup. a Schematic of the principle. The lm nanochannel was formed by inserting a gas bubble in a capillary.
The lm has length Land height h. Two connected electrodes were used for the electrical characterizations. bA snapshot of bubble formation within a
PDMS microuidic ow-focusing structure by high-speed camera (Photron, FASTCAM WX50). cA single bubble was conducted to a glass capillary and
remained static in microscopic view, where it appeared circular from the cross-sectional view (d). ePicture of setup. Two electrodes were inserted in the
pinched holes, and connected to a potentiostat for electrochemical measurements. fWave-like patterns were found by AFM at the inner surface of
capillary, creating an average roughness of 2.6 nm. gTypical IVcurves of a system with bubble (green) and without bubble (red). hAn equivalent circuit
of the system, consisting of resistances for the microchannel and lm nanochannel and capacitances for the bubble meniscus (C
b,cap
, gas/liquid interface)
and EDL of lm nanochannel (C
fch
, liquid/solid interface).
100 μm
0 s
800 s
ab c
2
10
8
6
G (nS)
4
2
0
0
pH = 8.5 pH = 8.5 pH = 8.5
pH = 4
pH = 4 pH = 4
Linear fitting
CV
EIS
–2
0
3
0 200 400 600 800 –0.6 –0.3 0.0 0.3 0.6
–3
I (nA)
I (nA)
I (nA)
t (s)
0 200 400 600 800
t (s)V (V)
–1
0
1
Fig. 2 The electrical characterization of the lm nanochannel. a The amplitude of lm nanochannel conductance measured by cyclic voltammetry
decreased in time, becoming saturated after a certain number of cycles, at pH values of 8.5 (top) and 4 (bottom), respectively. bTypical IVcurves at the
saturated states at pH values of 8.5 and 4 (dashed), showing the Ohmic behavior of the system. cThe evolution of system conductance measured by CV
(solid lines) gradually reached the value measured by EIS (dashed lines). Inset gure shows snapshot of a single bubble before (top) and after (bottom) the
electrical measurements, exhibiting a smoother surface after the measurements.
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Another point to be noted is that the bubble hardly moves in
the capillary under the applied electrical elds in our experiments,
except in case of a thick EDL at low salt concentration. However,
the motion of the bubble in low concentration salt not necessarily
induces a variation of lm thickness. According to previous
studies, the lm thickness still remains constant when the capillary
number (Ca) is <1043638. The evidence from our electrical
measurements also likely points to this conclusion (see Supple-
mentary Note 7). In this paper, we focused in the experiments on
the static or low Ca state (Ca is lower than 106, and the measured
data can be seen in Supplementary Table 1) of the lm
nanochannel with a small amplitude of applied voltage by CV
and EIS.
We rst investigated the effects of salt concentration and pH
on the conductance, since changes in the EDL signicantly
inuence the disjoining pressure, and hence the equilibrium lm
thickness. To eliminate the inuence of differences in bubble
length, we express the conductance of the lm nanochannel per
unit length, as G
fch
*=L·G
fch
. The displayed conductance is an
averaged value with an error bar from at least ve individual
measurements (measured data can be seen in Supplementary
Table 2 and 3). We calculated the error bars from ve or more
individual experiments using different capillaries, where the
majority of errors originated from the variation of wettability at
the capillary surface caused by the pre-cleaning process. A good
cleaning or coating of the surface can help to increase the
repeatability of lm conditions as we demonstrated in
immunosensing experiments (<4% error bars). Our experimental
results (green dots in Fig. 3a) show that the conductance per unit
length decreases by two orders of magnitude when the KCl
solution is diluted from 1 M to 0.01 mM. Our theoretical
prediction (black solid line) matches well with these experimental
results. The dashed line in Fig. 3a represents the bulk
conductance of a ctitious solid-state nanochannel with a xed
height of 11 nm. The system conductance is neither similar to
that of a solid-state nanochannel shown with colored solid lines
in Fig. 3a, which has a plateau at diluted concentrations
dependent on the surface charge density39, nor to that of a foam
nanochannel which has a conductance that remains of the same
order at all concentrations23. As we will illustrate later in this
paper, this results from the three-phase conguration of the lm
nanochannel with a concentration-dependent liquid lm
thickness.
From the measured conductance, we can calculate the lm
thickness by the following equation:
Gfch ¼2πrh
Lκð1Þ
where r,h,Lare the radius of the capillary, the height of the
nanochannel, and the length of the bubble, respectively.
Conductivity has contributions of bulk solution conductivity κ
b
and surface conductivity κ
s
, the latter originating from two
different interfaces liquid/gas and liquid/solid. The surface
conductivity can be derived from the theory of electrokinetic ow
abc
def
0 bar
1 bar 200 μm
pp
Bubble
10–1 Exp. data
Model
Exp. data
Exp. data
Ideal gas law
Exp. data 80
40
0
Ideal gas law
Model
Exp. data
PNP equations
Model
Exp. data C–0.5
PNP equations
Model
0.05 C·m–2
0.02 C·m–2
0.01 C·m–2
0.001 C·m–2
0.03 C·m–2
10–2
10–3
10–4
104
103
102
101
10–1
10–2
10–3
10–4
1200
L (μm)
800
600
Rfch (MΩ)
400
200
400
100
102
101
100
3456
pH
789
3
4
2
0
0 500 1000
P (mbar)
456
pH
789
10–3 10–2 10–1 100101
C (mM)
10210310–3 10–2 10–1 100101
C (mM)
102103
Gfch* (nS·m)
Gfch* (nS·m)
Gfch* (×10–3 nS·m)
h (nm)
h (nm)
h (nm)
Fig. 3 The tunable height and length of lm nanochannel with characterizations. a The measured conductance of lm nanochannel per unit length at pH
8.5 (dots), with theoretical predictions (black solid line). The colored lines are theoretical conductance of a ctitious solid-state nanochannel with different
surface charge densities and a height of 11 nm. bThe calculated lm thickness from the normalized conductance as a function of KCl concentration at pH
8.5 by theoretical approach (circle dots) and simulations by PNP equations (square dots). Dashed line shows the dependence of the Debye length on
concentration. cThe normalized conductance with 10 mM KCl solution. dThe calculated lm thickness as a function of pH at 10 mM solutions. Solid lines
are the theoretical predictions described in Methods section. eBubble shrinkage by applied pressure. The length of the lm channel decreases with
increasing external pressure of liquid phase. Snapshot of a single gas bubble when the applied external pressure increases from 0 to 1 bar. The length
decreases to nearly half value when 1 bar pressure applied on the microchannel. fThe decrease of bubble-length (upper graph, green squares)-induced
decrease of lm nanochannel resistance (upper graph, orange squares) as a function of applied pressure. Solid lines were derived from Eq. 1with length
predicted by Ideal Gas Law. The normalized resistance of lm nanochannel (lower graph, dots) and channel height (lower graph, dots) remain constant due
to the persistence of capillary pressure (contact angle of bubble). The error bars are the standard deviation of ve or more individual results.
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in parallel-plate nanochannels and has the following form40:
κs¼μσ
1þσ2
ðÞ
h1þ1
2πlBμη
 ð2Þ
where μ,l
B
,η,σ
1
, and σ
2
are the ionic mobility, Bjerrum length,
liquid viscosity, and charge density of gas/liquid and solid/liquid
interfaces respectively. The values of σ
1
and σ
2
were derived from
previous studies4144, and we experimentally characterized the
zeta potential of the solid/liquid interface by measuring the
streaming current in the capillary (see Supplementary Note 8;
measured data can be seen in Supplementary Table 4). It needs to
be noted that the accuracy of channel height estimation by Eq. 2
at low concentration is not as high as in high concentrations, as
the surface conduction contribution can no longer be ignored in
the diluted solutions. However, the height of lm channel can still
be estimated, since the conductance change induced by the height
change is comparable to the contribution of the surface
conductance in our low surface charge system. More detailed
information can be found in Supplementary Note 9. The
theoretical predictions demonstrate that the contribution from
the surface conductivity depends on the lm height for the entire
range of salt concentrations. This is different from the solid-state
nanochannel where the conductance reaches a plateau value due
to the overlap of EDL where the conductance is becoming
independent of channel height. In our lm nanouidic channel,
the conductance change due to a change in lm thickness can not
be neglected, so that we could derive the lm thickness by
conductance measurements. Substituting Eq. 2in 1, we obtain
h¼G
fch
2πrμσ
1þσ2
ðÞ1þ1
2πlBμη

=κbð3Þ
Finally, substituting all physical constants (see Methods) and
the measured conductance into Eq. 3, we can derive the height of
the nanochannel shown as open circle dots in Fig. 3b. The height
of lm nanochannel can also be estimated by numerical
simulations by Poisson-Nernst-Planck (PNP) equations, shown
as open square dots in Fig. 3b. The estimated lm height from
both calculations and simulations did not represent a signicant
difference, and more details of the simulations can be found in
Supplementary Note 9. Assuming the zeta potential remains
constant in various concentrations, the Eq. 6in Methods can be
simplied as exp(λh)=const, where the λis reciprocal of the
Debye length. According to the denition of Debye length λ1=
(ε
0
ε
r
k
B
T/e2CN
A
)1/2 where ε
r
,ε
0
,k
B
,T,e, and N
A
are relative
permittivity of the liquid, electrical permittivity of vacuum,
Boltzmann constant, temperature, elementary charge, and
Avogadro constant, respectively, we know the lm thickness is
proportional to C0.5 which is shown as the dashed line in
Fig. 3b, matching well with our experimental results. The
relationship between channel height and the normalized
conductance of the lm nanochannel can be seen in Supplemen-
tary Note 9. The theory (solid line) slightly deviates from the
experimental data at diluted solution, due to the use of zeta
potential at gas/liquid surface tted from previous studies (See
Supplementary Note 8)4143.
As already briey described in the device section, the thickness
of the lm nanochannel is determined by a balance between the
disjoining pressure and the capillary pressure. The disjoining
pressure at low salt concentrations (lower than 300 mM) is
dominated by the long range electrostatic repulsion forces
between the solid/liquid and gas/liquid interfaces, resulting in a
high disjoining pressure and a thick lm. The derived lm
nanochannel thickness ranges from 11 nm to 920 nm for salt
concentrations from 1 M to 0.01 mM, well in accordance with the
theoretical values. In high concentration solutions (higher than
300 mM), the short range van der Waals forces start to govern
disjoining pressure and a minimal lm thickness of 11 nm is
reached. The thinnest lm was in the range of common black
lms, due to the surface tension and wettability (CA equals to
25°) in our system45. In addition, the roughness of the capillary
inner surface probably induces a thicker equivalent lm.
The lm thickness is also expected to be pH-dependent, as a
higher pH value increases surface charge density and hence the
electrostatic contribution to the disjoining pressure. We char-
acterized the conductance of the lm nanochannel per unit length
for pH values ranging from 8.5 to 3, similar as above. The results
in Fig. 3c demonstrate for a 10-mM KCl solution that the
conductance decreases nearly an order of magnitude in this pH
range, as well as the calculated channel height in Fig. 3d (32 nm to
10 nm). The lowest pH value is close to the isoelectric point of
both glass surface (pH 2.8 ± 0.246) and air/water surface (pH3.0 ±
0.542), where both interfaces are nearly electroneutral.
Besides the height, the length of the lm channel can be
adjusted, as a compressible gas bubble is used. To keep the bubble
in a static position in the capillary, we applied identical external
pressures at the two ends of the microchannel (Fig. 3e). With
applied pressures increasing from 0 to 1 bar, the bubble length
gradually shrinks from 1100 µm to 500 µm (Fig. 3e), with the
effects by pressure increase shown in Supplementary Note 10.
The ideal gas law (pV =nRT, where p,V,n,T, R are the pressure,
volume, the number of moles, thermodynamic temperature of
ideal gas, and ideal gas constant respectively) well predicted the
bubble-length decrease (black solid line in Fig. 3f).
The change of bubble length was observed by the increase of
conductance as it is proportional to the bubble length according
to Eq. 1. We found that the normalized conductance of the lm
nanochannel (G
fch
*) remained constant at varying external
pressure, indicating a constant height of the lm nanochannel
(Fig. 3f). This is in accordance with the equation in our
theoretical predictions in the Methods section. The lm thickness
is determined by the equilibrium of disjoining pressure and
capillary pressure, the latter of which relates to the contact angle
of the bubble that remained constant. The constant capillary
pressure causes a constant lm thickness even when the absolute
pressures in both gas and liquid phase increase.
Summarizing, our results demonstrated that the dimensions
both height and lengthof the lm nanochannel are widely and
independently tunable, the height by adjusting salt concentration
or pH and the length by applying external pressure. A
recongurable dimension of lm nanochannel may not only
help to decrease the costs and technical barriers of making
nanouidic devices by avoiding the necessity of fabricating
numerous nanouidic devices with different geometries for
specic uses. As we will demonstrate later in this paper, the lm
nanochannels also can be operated as another type of highly
sensitive (bio)chemical sensors, using the property of wettability.
ICP in lm nanochannel. Nanouidic channels can generate ion
concentration polarization (ICP) due to their ion permselectivity,
generally allowing predominantly cations to pass11,47. ICP causes
salt accumulation and depletion at the two opposite ends of the
nanochannel during prolonged passage of current. The ICP
phenomenon is useful in biomolecule pre-concentration, seawater
desalination, and more11,48,49. Here we demonstrate that the lm
nanochannels also give rise to ICP.
Two different concentrations (70 µM and 3 mM) of sodium
tetraborate buffer solution at pH 8 (STB, Na
2
B
4
O
7
) were used in
the experiments, with addition of 30 μMuorescein as uorescent
concentration indicator. Depletion of uorescein (dark) was
readily observed in 70 µM STB solution after applying 10 V DC
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voltage for 2 min (Fig. 4b), and became more obvious over time
(Fig. 4cf), while this phenomenon was not observed in the high
concentration STB solution (Fig. 4gl). Fluorescein enrichment
was not obvious on the opposite side of the bubble, probably due
to photobleaching by the continuous UV excitation50. The
recorded conduction current under DC applied voltage shows a
continuous decrease and nally saturation for diluted electrolyte
solution, while nearly remaining constant at high concentration
solutions (see Supplementary Note 11). The current-limiting
effects at low salt concentration can be attributed to the high
resistance of the depletion zone created.
Label-free immunosensing by BFN. Nanouidic channels have
been used for biosensing using the principle of surface con-
ductance (the conductance in the EDL), because a (bio)chemical
binding reaction such as the biotin-avidin binding13,5153 causes a
change of surface charge density, which causes a conductance
change in diluted solution (Fig. 5a)13.
We will use the sensitivity of a conductivity-based immuno-
sensor as a critical performance indicator, which we dene as the
ratio of the conductance after G
SAv
and before G
biotin
the SAv
reaction:
Sensitivity ¼GSAv=Gbiotin
We will demonstrate that the sensitivity of immunosensing in a
lm nanochannel is enhanced due to the change of wettability in
addition to changes in surface charge density.
We coated the inner surface of the capillary by applying a self-
synthesized PLL-g-OEG-Biotin54,55 solution to the capillary inner
surface. The cationic macromolecule Poly-L-Lysine (PLL)
assembled on the negatively charged glass capillary surface, and
oligo ethylene glycol (OEG) was used to block non-specic
binding54. Successful functionalization of the capillary with biotin
and reactivity of the immobilized biotin was demonstrated using
subsequent binding of uorescein isothiocyanate-labeled Strepta-
vidin within 12 h as microscopically observed (Fig. 5b). We then
pumped liquids through the capillary for the surface coating
(Biotin) and binding reaction (SAv), and only then generated a
single bubble in the capillary to form a lm nanochannel for the
measurement of conductance. (see Methods) Although pressure-
driven ow was used to accelerate the binding reactions, our
system was still operated in the mass transport-limited regime,
with a Damkohler number (D
a
) of 70.
We found a clear change of the contact angle, before (CA is
~50°) and after the specic SAv reaction (CA is ~28°), probably
caused by the increase of surface charge density after binding
(Fig. 5c). The increased wettability on SAv binding decreases the
contact angle and importantly also increases the disjoining
pressure and lm thickness (see the theory in Methods section).
We characterized the conductance of the biotin-coated lm
nanochannel by CV and EIS in phosphate-buffered saline (PBS)
solution, to obtain the conductance changes caused by the Biotin-
Avidin reaction. The IVcurves at 0.001× PBS demonstrate an
obvious conductance change after SAv binding (Fig. 5d), enabling
to derive the conductance by linear tting of IVcurves. We
found that the lm conductance at 0.001× PBS increased by
nearly an order of magnitude, which is higher than the
conductance increase found in a solid-state nanochannel
(1.23.4)13,51. We attribute this to a major factor of wettability
change, and a minor factor of surface conductance change, as we
will discuss below. We repeated the conductance characterization
after biotin-SAv reaction at various PBS concentrations (Fig. 5e).
The error bars in Fig. 5were calculated from the repeated
electrical measurements from a single capillary with ve or more
generated bubbles. The errors of <4% demonstrate the reliability
of the electrical detection. The conductance behaves similar to the
bulk solution conductance of a solid-state nanochannel, since a
ctitious conductance (dashed line) of a solid-state nanochannel
matched well to our results. The equivalent height of the
nanochannel after SAv reaction is 7 nm (green), while the
equivalent height is only 0.07 nm (red) before the SAv reaction,
indicating that a stable liquid lm at the biotin-coated surface did
not exist.
The sensitivity as immunosensor was dened by the ratio of
the conductance after and before the SAv reaction: G
SAv
/G
bio
,asa
critical performance indicator. Figure 5f shows that the sensitivity
0 min
2 min
4 min
6 min
8 min
10 min
0 min
2 min
4 min
6 min
8 min
10 min
200 μm
g
h
i
j
k
l
a
b
c
d
e
f
Fig. 4 Ion concentration polarization by lm nanochannel. afICP effects were observed in 70 μM STB solution, while not in 3 mM STB solution (gl),
with 30 μMuorescein used as uorescence dye. The images were recorded every 2 min, to prevent the photobleaching of uorescence. White solid lines
were drawn to outline the capillary and the position of the bubble.
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of the lm nanochannel is higher than reported in the data for
solid-state nanochannels in diluted solution, including conduc-
tance change (approximates to 4)13. Moreover and surprisingly,
we found that the sensitivity of the lm nanochannel is even
higher in the high concentration solutions, with a maximal
sensitivity of 233 in 1× PBS solution.
To illustrate the mechanism of sensitivity enhancement and
effects of the salt concentration, we separated the contributions
to the sensitivity from the surface conduction and wettability.
We derived the contribution from the surface conduction using
the zeta potential of the biotin and SAv surface13,asshownin
Supplementary Note 12. We found that the sensitivity due to
surfaceconductance(squarebluedotsinFig.5f) behaved
similarly to that in the solid-state nanochannel but at nearly
half the value, since only the solid/liquid interface can be coated
and functional for the sensing. By subtracting the contribution
of surface conduction, we can nd that the contribution from
the change of wettability (circular red dots in Fig. 5f) is
predominant.
In diluted solutions, the contribution of the surface conduc-
tance can no longer be ignored. However, the sensitivity caused
by the surface conductance change is weaker than by the
Biotin-SAv
Gas bubble
Gas bubble
Biotin
Biotin
50°
50 μm
Biotin-SAv
28°
Biotin
Biotin-SAv
a
b
c
e
d
f
gh
ij
100 μm
10–1
10–2
10–3
10–4
10–5
Gfch* (nS·m)
[bio-SAv]
[bio-SAv]
Gfch* (nS·m)
I (nA)
GSAV/Gbiotin
GSAV/Gbiotin
GSAv/Gbiotin
GSAv/Gbiotin
CSAv (μM)
C (mM)
CSAv (μM)
C (mM)
V (V)
10–6
10–2
103
102
101
100
10–1
10–3
10–4
10–5
10–6
0.001
2.0 1 nM SAv 50 nM SAv 50 nM SAv
200 nM SAv 200 nM SAv
Biotin Film nanochannel
Solid nanochannel
Wettability contribution
contribution
Biotin-SAv
Biotin
Biotin-SAv
Linear fitting
0.001× PBS
Bulk conductance
10 nM SAv
1 nM SAv
10 nM SAv
SAv, 0.01× PBS 0.01× PBS
SAv, 1× PBS 1× PBS
Solid nanochannel
Biotin
1.5
1.0
0 100
100
10
1
90
60
0.15 1.5 15 150 1500
1.0
0.5
0.5
30
0.4
0.2
0.0
–0.2
–0.4
–10 –5 0 5 10
200 300
Time (min) Time (min)
400 500 600 0 30 60 90 120
1.0
0.5
0.0
0.01 0.1 1 10 0.001 0.01 0.1 1 10
10–7
10–1 100101102103
Fig. 5 Label-free immunosensing by lm nanochannel. a Schematic picture illustrating the principle of sensing the biotin-SAv reaction. bThe
functionalization with biotin (top) and subsequent successful binding of avidin on the capillary surface (bottom) was demonstrated by the uorescence of
FITC-SAv. cA change of contact angle in the capillary was observed after the immobilization of SAv. dThe IVcurves show a strong change of the
conductance induced by the biotin-SAv binding reaction (19 μM SAv). eThe bubble length-normalized conductance of the lm nanochannel G
fch
*was
derived by linear tting in 103× to 10× PBS solutions. The dashed lines are the theoretical conductance of a ctitioussolid-state nanochannel neglecting
the surface conductance. fSensitivity (G
SAv
/G
bio
)oflm nanochannels (green) as function of salt concentration, compared to that of a polysilicon
nanochannel13 (orange column). The blue square dots represent the contribution from the change of zeta potential, while the red circular dots represent
the contribution from the wettability change. gThe kinetics of the biotin-SAv reaction in 1 nM (orange square dots) and 10 nM (green circle dots) SAv
solutions, with predicted ratio (0 to 1) of occupied biotin sites (right axis, solid lines). hThe reaction kinetics in 50 nM (dark blue dots) and 200 nM (light
blue dots) SAv solutions, with predicted ratio of biotin-SAv binding (right axis, solid lines). iThe bubble-length normalized lm nanochannel conductance
G
fch
*as a function of SAv concentration for 0.01× and 1× PBS solutions. The dashed lines represent the measured conductance before biotin-SAv binding at
0.01× (blue) and 1× (red) PBS, while the dots are measured G
fch
*after SAv binding. jCalculated sensitivity as a function of SAv concentrations in 0.01× and
1× PBS solutions. The solid line represents data from a solid-state nanochannel51. The error bars are the standard deviation obtained from ve or more
individual measurements.
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wettability change as can be seen from the sensitivity of solid state
nanochannels13, since the surface conductance linearly responds
to the change of surface charge density (κ
s
is proportional to σ)51.
As the surface conduction plays a more important role in diluted
solutions, the system sensitivity decreases and approaches that of
the solid-state nanochannel.
In concentrated solutions, the conduction can be estimated as
G
fch
*~2πhκ
b
h, where the height dominates the conductance. For
a solid state nanochannel the height remains constant, hence it
will not present a conductance variation after reaction. Conse-
quently, solid states nanochannels cannot be used for biosensing
at high salt concentration when using the principle of surface
conductance change. However, in a lm nanochannel where both
wettability and surface charge determine the thickness of the
wetting lm, conductance can be used for biosensing. The
immobilization of the SAv molecules results in a change of both
wettability and surface charge density. A well-wetting surface
results in a small contact angle and large Laplace pressure, and a
thick liquid lm, which was described in Supplementary Eq. 16 in
Supplementary Note 12. The critical inuence of the wettability
can be seen by the results of pH effects as a control group (Fig. 3c,
d). The normalized conductance only increased by one order of
magnitude for a pH change from 3 (electroneutral surface) to 8.5
under a constant CA (25°). This change, due to the increase of
surface charge density, is much smaller than the change observed
in the immunosensing experiment. Summarizing, due to the
contributions of both wettability and surface conduction, the
label-free sensing of biotin-SAv reaction can be electrically
measured over a full range of salt concentrations in the lm
nanochannel.
To investigate the minimum concentration and binding
kinetics of SAv, we measured the conductance change of the
liquid lm performing the binding reaction in a 1× PBS solution
in time. We hereby followed the procedure Reactions and
measurements in the Methods section. We found a minimum
detectable SAv concentration of 10 nM, with a sensitivity equal to
1.21.7 due to the small change of CA (Fig. 5g). Unfortunately,
lower concentrations (lower than 10 nM) of SAv could not be
detected, probably due to mass transport limitations in the
microcapillary, where the Damkohler number was 70 1
(Da¼kabiotin½δ
DSAv , where k
a
, [biotin], δ,D
SAv
are association rate
constant, surface density of biotin, thickness of depletion layer
and diffusion coefcient of SAv, respectively). Here the
Damkohler number D
a
represents the ratio of reaction rate and
diffusive mass transport rate. The mass transport rate determines
the binding rate at D
a
>1, while the reaction rate is dominating at
D
a
< 1. To further decrease the minimum detectable concentra-
tions, working in a ner capillary will be helpful to increase mass
transport.
At concentrations above 50 nM, a change of CA could already
be microscopically observed, inducing a sensitivity of 5060
(Fig. 5h). Our results show that binding can already be measured
at an early stage by the liquid lm nanochannel. For example, for
200 nM SAv the change of CA saturated at a sensitivity of 60
within 10 mins. Thus not only the sensitivity is enhanced as
compared to solid-state nanochannels, but also the speed of
sensing is increased. This possibly indicated a nonlinear response
of the binding kinetics to the micro-bubble contact angle change
in the capillary. Although the real-time characterizations of the
SAv binding ratio at the capillary inner surface is technically not
easy in our current device, it would be interesting to investigate
the connections between binding kinetics and contact angle
change in the future work. The decrease of sensitivity in 200 nM
SAv was possibly caused by the damage to the biotin lm at the
capillary surface by the hydrodynamic shear stress of the
pressure-driven ow. A similar phenomenon was found in
previous work in solid-state nanochannels51. More details about
our theoretical model can be found in Supplementary Note 13.
Finally, by using the lm nanochannel, we could quantify the
minimum detectable SAv concentration at the equilibrium states,
except the SAv concentrations lower than 10 nM. We took the
conductance at concentration of 1 and 10 nM SAv after 10 h
binding reactions in Fig. 5i, since a longer reaction is not useful in
the clinical diagnostic. To separately demonstrate the effects from
wettability and surface conduction, we chose two concentrations
of PBS solution 0.01× PBS and 1× PBS, where the former
measurements are expected to be determined by changes in
surface conduction and the latter by wettability changes.
To perform the binding reactions, SAv solutions with
concentrations ranging from 1 nM to 19 μM were used, following
the procedure in Reactions and measurements. Figure 5i shows
the normalized conductance of the lm channel after biotin
modication (dashed lines) and SAv binding (dots) for the two
PBS concentrations. The normalized conductance after SAv
binding signicantly increased and remains at the same order of
magnitude as they reached the equilibrium states when the SAv
concentration is over 50 nM.
Using our denition, we calculated the sensitivity as a function
of SAv concentration at 0.01× PBS and 1× PBS (Fig. 5j).
Compared to the sensitivity in solid state nanochannels (solid line
derived from a previous study51), the sensitivity of the lm
nanochannel is higher for both diluted and concentrated
solutions. For diluted solutions, the wettability-induced height
change contribution is comparable to that of the surface
conduction, thus increasing the sensitivity of the lm nanochan-
nel. For high concentration solutions, the height change inuence
is predominant, with the sensitivity reaching the magnitude of
100 at 1× PBS. Finally, the lm nanochannel can be useful for the
electrical measurement of binding equilibria for immunosensing.
Some further minor factors determining the sensitivity of the lm
nanochannel are discussed in Supplementary Note 14.
Our results demonstrate that the lm nanochannel has great
promise for label-free biosensing, with a maximum sensitivity
that is two orders of magnitude higher than in a solid state
nanochannel. Besides, the biosensing works over the entire
common range of salt concentrations (0.1 mM to 1000 mM), with
the optimal working condition actually at the physiological
conditions of a 1× PBS solution. By using the mechanism of CA
change, the binding can be measured at an early stage before
equilibrium binding is reached, accelerating the speed of sensing.
These results indicate that the wetting-based sensing allows
working at the physiological salt concentrations, which can be
very useful for clinical diagnostics. Furthermore, lm nanochan-
nels are easy-to-make, low cost, and as demonstrated possess a
number of unique properties which are attractive for further
development and study.
Discussion
We reported a liquid lm nanochannel produced by inserting a
gas bubble in a cylindrical glass capillary. We electrically char-
acterized the lm conductance, and calculated the lm thickness.
We found that the height and length of the lm nanochannel can
be individually tuned by EDL thickness and applied pressure,
which is important for making dimension-recongurable nano-
channels for non-specic uses. We demonstrated that the lm
nanochannels share some fundamental properties with other
nanouidic devices, such as ion concentration polarization.
Finally, we demonstrated that the lm nanochannel can be used
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as another type of label-free biosensor using the principle of
wettability change. With the biotin-SAv binding reaction as
model, our results indicate that the maximal sensitivity of the lm
nanochannel can be two orders of magnitude higher than for a
solid state nanochannel. This surprising result can be explained
by a binding reaction-induced change of surface wettability that
causes a large change of lm thickness. In addition, the binding
can be measured at an early stage before the equilibrium state is
reached, accelerating the speed of sensing. The optimal working
concentration is that of physiological solution (1× PBS), opening
up attractive possibilities for clinical analytical applications.
Methods
Device fabrication. The PDMS chip was fabricated by standard photolithography
processes. A layer of 180 μm negative photoresist (Microchem, SU-8 2075) was
spin-coated on a polished silicon wafer. The photoresist was then exposed using a
mask and mask aligner with 24 mW cm2UV light density for 15 s. After devel-
oping the microstructures for 5 min, we obtained a SU8 mold with 180μm height
microchannels. PDMS was mixed with curing agent at a ratio of 10:1, poured on
the lithography wafer and baked at 60 °C for 4 h. The PDMS chip was then fab-
ricated by standard PDMSPDMS bonding technique using an oxygen plasma
cleaner (Harrick Plasma, PDC-002). A channel structure of 360 μm width was
designed for capillary connection. After inserting the capillary into the PDMS
channel, some uncured PDMS was applied at the junction of PDMS and capillary,
to ensure water tightness after curing.
Hydrogen peroxide (30% H
2
O
2
) and diluted potassium hydroxide (0.1 M KOH)
were sequentially injected for 15 and 45 min respectively, as a pretreatment of the
capillary surface to have a clean and well wettable surface. Then, the solutions
prepared for experiments were ushed through the capillary for at least 45 min
before the electrical measurements, to obtain an equilibrium state of the surface
chemistry, especially when working at different pH solutions.
The cleaning of the capillary can be repeated per 48 h ensuring the wetting state
of the capillary. The capillary can be reused for many times by a drying process
(100 °C for 0.5 h) and cleaning procedure, unless becoming contaminat ed or
physically breaking down.
Solution preparation. The solutions used for conductance measurements were
prepared by rst dissolving the monovalent salt KCl (from Sigma-Aldrich) at 1 M
in DI water (Merck Millipore, D24 UV). The solutions of other concentrations
were prepared by diluting this solution. The pH value of the solution was adjusted
with diluted KOH and HCl, avoiding other ionic species introduced in the elec-
trolyte solution. The solutions were re-prepared every 24 h to avoid the absorption
of CO
2
. The solution pH was characterized with a pH meter (LeiCi, PHS-25), while
the conductivity of the solution was characterized with a conductivity meter
(Mettler Toledo, FE38). All experiments were performed at room temperature
(22 °C).
Electrical characterization. The gas bubble was generated by operating a
computer-controlled pressure pump while monitoring under a Microscope (Zeiss,
Axio Observer A1). When one bubble had entered the capillary, the remainder of
the gas bubbles were removed from the PDMS channels, ensuring one single
bubble remaining. Homemade Ag/AgCl electrodes were used to minimize over-
potentials of the electrochemical reactions. They were connected to a pico-ammeter
voltage source station (Keithley 6482) for CV characterizations controlled by in-
house LabVIEW software, and an electrochemical workstation (CHI660E) for EIS
measurements. The CV characterizations were operated using a triangular wave
voltage with scanning rate of 0.1 V s1and amplitude of 0.5 V for at least 800 s. As
a control experiment, we operated the EIS characterizations at 0.5 V amplitude of
voltage with frequencies ranging from 1 to 1k Hz immediately after the CV.
Biotin and SAv preparation. PLL (1530 kDa) and FITC-SAv were purchased
from Sigma-Aldrich. EZ-Link N-hydroxysuccinimidyl ester NHS-OEG4-Biotin was
purchased from Thermo SCIENTIFIC. Streptavidin was purchased from J&K
Scientic. PLL-g-OEG4-Biotin was synthesized by adding NHS-OEG4-Biotin into
a 40-mg mL1solution of PLL dissolved in 50 mM Na
2
CO
3
, and reacting for 5 h at
room temperature.
Reactions and measurements.Werst pumped the self-synthesized PLL-g-OEG-
Biotin through a microcapillary for a homogeneous coating of Biotin on its inner
surface for at least 2 h. Then we pumpe d specic concentrations of SAv solutions in
for the binding reactions, without bubble insertion. Only then, we generate a single
bubble with specic PBS solutions in the capillary, to form the liquid lm nano-
channel for the electrical measurements.
Surface modication. The capillary was rst rinsed with 0.1× PBS (pH 7.2; 10×
PBS contains 1.55 M KCl, 0.015 M KH
2
PO
4
, and 0.027 M K
2
HPO
4
) for 2 h, then
immersed in a 1-mg mL1solution of biotin in 10 mM 4-(2-hydroxyethyl)-1-
piperazineethanesulfonic acid (HEPES) for 1 h to complete the surface modica-
tion with biotin. The capillary was then immersed for 1 h in a 200-nM FITC-SAv
solution (also in 10 mM HEPES) to verify the modication result of biotin and to
test the specic binding. A 0.1× PBS solution with 1 mg mL1SAv (19 μM), was
used to research the effect of specic binding on channel conductance, immersing
the capillary for 10 h. Other SAv solutions of different concentration were diluted
from 1 mg mL1stock solution, and immersion time still kept as 10 h. All the
experiments were performed at room temperature.
Theoretical predictions. The thickness of the liquid lm, as previously reported,
results from an equilibrium between capillary pressure p
c
and disjoining pressure
Π
d
, expressed as56:
Πd¼pc¼PgPext þγcosθ
rð4Þ
where P
g
and P
ext
are the gas pressure inside the bubble and the external pressure.
Furthermore, γ,r,θare interfacial tension, inner radius of capillary, and wetting
angle, respectively. As the pressure difference between inside and outside of the
bubble is determined by the meniscus curvature, we can derive the capillary
pressure as pc¼γcosθ
r. The contact angle of the bubble can be optically character-
ized in the capillary. (See Supplementary Note 15). The disjoining pressure is in
general seen as composed of two terms, one representing van der Waals forces and
the other electrostatic interaction Π
d
=Π
vdW
+Π
el
, where the van der Waals
pressure resulting from molecular interactions can be calculated as57
ΠvdW ¼ A
6πh3ð5Þ
Here Ais the Hamaker constant of the medium in the liquid lm, and hindicates
its thickness. The electrostatic repulsion can be calculated as:
Πel ¼64kTC1γ1γ2exp λhðÞ ð6Þ
γi¼tanh zeζi
4kT

;i¼1;2ð7Þ
Here k,T,C
,1/λ,h,e, and zare the Boltzmann constant, temperature, bulk
number density of the electrolyte ions, Debye length, lm thickness, elementary
charge, and ionic valence, respectively. γ
1
,γ
2
are the reduced surface potentials of
the liquid/air and liquid/solid interfaces, with corresponding zeta potentials ζ
1
,ζ
2
respectively. Since it is still nearly impossible to characterize the liquid/solid surface
potential58, here we took the zeta potential instead of the surface potential to
estimate the thickness of the liquid lm. According to the Supplementary Eq. 17,
this deviation causes a negligible difference on the calculated liquid lm. Since the
characterization of zeta potential was performed when using pure gas bubbles
without surfactants, the measured value might already take the slippage into
account. Here we did not take additional slippage effects into account in the
calculations. Finally, we can derive the theoretical value of liquid lm thickness, as
well as the predicted lm resistance shown in Fig. 3. It needs to be noted that the
theory described above is only valid for static liquid lms or low Ca number.
Physical constants.μ: ionic mobility, 8.1 × 109m2s1V1
η: liquid viscosity, 1.01 × 103Pa s
l
B
: Bjerrum length, 0.7 nm
γ: interfacial tension, 7.2 × 102Nm
1
e: elementary charge, 1.6 × 1019 C
A: Hamaker constant, 1.03 × 1021 J
k: Boltzmann constant, 1.38 × 1023 JK
1
T: temperature, 295.15 K
k
a
: association rate constant, 5 × 106M1s1
[biotin]: surface density of biotin, 5.5 × 108mol m2
δ: thickness of depletion layer, 1.5 × 105m
D
SAv
: diffusion coefcient of SAv, 6 × 1011 m2s1
Data availability
The data that support the plots within this paper and other nding of this study are
available from the corresponding author upon reasonable request.
Received: 17 June 2019; Accepted: 15 January 2020;
References
1. Whitesides, G. M. The origins and the future of microuidics. Nature 442,
368373 (2006).
2. Sparreboom, W., van den Berg, A. & Eijkel, J. C. T. Principles and applications
of nanouidic transport. Nat. Nanotechnol. 4, 713 (2009).
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3. Howorka, S., Cheley, S. & Bayley, H. Sequence-specic detection of individual
DNA strands using engineered nanopores. Nat. Biotechnol. 19, 636639
(2001).
4. Eijkel, J. C. T. & van den Berg, A. Nanouidics: what is it and what can we
expect from it? Microuid. Nanouid. 1, 249267 (2005).
5. Napoli, M. T., Eijkel, J. C. T. & Pennathur, S. Nanouidic technology for
biomolecule applications: a critical review. Lab Chip 10, 957985 (2010).
6. Sparreboom, W., van den Berg, A. & Eijkel, J. C. T. Transport in nanouidic
systems: a review of theory and applications. New J. Phys. 12, 015004 (2010).
7. Eijkel, J. C. T. Liquid slip in micro- and nanouidics: recent research and its
possible implications. Lab Chip 7, 299301 (2007).
8. Eijkel, J. C. T. & van den Berg, A. Nanouidics and the chemical potential
applied to solvent and solute transport. Chem. Soc. Rev. 39, 957973 (2010).
9. Shui, L., van den Berg, A. & Eijkel, J. C. T. Scalable attoliter monodisperse
droplet formation using multiphase nano-microuidics. Microuid.
Nanouid. 11,8792 (2011).
10. Sanghavi, B. J., Varhue, W., Chavez, J. L., Chou, C. & Swami, N. Electrokinetic
preconcentration and detection of neuropeptides at patterned graphene-
modied electrodes in a nanochannel. Anal. Chem. 86, 41204125 (2014).
11. Kim, S. J., Ko, S. H., Kang, K. H. & Han, J. Direct seawater desalination by ion
concentration polarization. Nat. Nanotechnol. 5, 297301 (2010).
12. Schoch, R. B., Han, J. & Renaud, P. Transport phenomena in nanouidics.
Rev. Mod. Phys. 80, 839883 (2008).
13. Karnik, R., Castelino, K., Fan, R., Yang, P. & Majumdar, A. Effects of
biological reactions and modications on conductance of nanouidic
channels. Nano Lett. 5, 16381642 (2005).
14. van der Heyden, F. H. J., Bonthuis, D. J., Stein, D., Meyer, C. & Dekker, C.
Power generation by pressure-driven transport of ions in nanouidic
channels. Nano Lett. 7, 10221025 (2007).
15. Siria, A., Bocquet, M. L. & Bocquet, L. New avenues for the large-scale
harvesting of blue energy. Nat. Rev. Chem. 1, 0091 (2017).
16. Whitesides, G. M. What comes next. Lab Chip 11, 191193 (2011).
17. Kwok, H., Briggs, K. & Tabard-Cossa, V. Nanopore fabrication by controlled
dielectric breakdown. PLoS ONE 9, e92880 (2014).
18. Siwy, Z. et al. Ion transport through asymmetric nanopores prepared by ion
track etching. Nucl. Instrum. Methods Phys. Res. Sect. B 208, 143148 (2003).
19. de Vreede, L. J., van den Berg, A. & Eijkel, J. C. T. Nanopore fabrication by
heating Au particles on ceramic substrates. Nano Lett. 15, 727731 (2015).
20. Huh, D. et al. Tuneable elastomeric nanochannels for nanouidic
manipulation. Nat. Mater. 6, 424 (2007).
21. Kim, B. et al. Tunable ionic transport for a triangular nanochannel in a
polymeric nanouidic system. ACS Nano 7, 740747 (2013).
22. Bonhomme, O., Liot, O., Biance, A. L. & Bocquet, L. Soft nanouidic transport
in a soap lm. Phys. Rev. Lett. 110, 054502 (2013).
23. Bonhomme, O., Mounier, A., Simon, G. & Biance, A. L. Surface conductivity
measurements in nanometric to micrometric foam lms. J. Phys. Condens.
Matter 27, 194118 (2015).
24. Joly, L., Detcheverry, F. & Biance, A. L. Anomalous ζpotential in foam lms.
Phys. Rev. Lett. 113, 088301 (2014).
25. Wasan, D. T. & Nikolov, A. D. Spreading of nanouids on solids. Nature 423,
156159 (2003).
26. Bonn, D., Eggers, J., Indekeu, J., Meunier, J. & Rolley, E. Wetting and
spreading. Rev. Mod. Phys. 81, 739805 (2009).
27. Hammoud, N. H., Trinh, P. H., Howell, P. D. & Stone, H. A. Inuence of van
der Waals forces on a bubble moving in a tube. Phys. Rev. Fluids 2, 063601
(2017).
28. Chaudhury, K. & Chakraborty, S. Scaling regimes of thermocapillarity-driven
dynamics of conned long bubbles: effects of disjoining pressure. Phys. Rev. E
91, 033021 (2015).
29. Takhistov, P., Indeikina, A. & Chang, H. C. Electrokinetic displacement of air
bubbles in microchannels. Phys. Fluids 14,114 (2002).
30. Nie, J. et al. Power generation from the interaction of a liquid droplet and a
liquid membrane. Nat. Commun. 10, 2264 (2019).
31. Husale, S., Grange, W., Karle, M., Bürgi, S. & Hegner, M. Interaction of
cationic surfactants with DNA: a single-molecule study. Nucleic Acids Res. 36,
14431449 (2008).
32. Zheng, B., Tice, J. D., Roach, L. S. & Ismagilov, R. F. A dropletbased,
composite PDMS/glass capillary microuidic system for evaluating protein
crystallization conditions by microbatch and vapordiffusion methods with
onchip Xray diffraction. Angew. Chem. 43, 25082511 (2004).
33. von Klitzing, R. Effect of interface modication on forces in foam lms and
wetting lms. Adv. Colloid Interface Sci. 114, 253266 (2005).
34. Kaupp, S. & Wätzig, H. Characterization of inner surface phenomena in
capillary electrophoresis capillaries by electron microscopy, atomic force
microscopy and secondary ion mass spectroscopy. J. Chromatogr. A 781,
5565 (1997).
35. Churaev, N. V. Wetting lms and wetting. J. Phys. 23, 975987 (1988).
36. Bretherton, F. P. The motion of long bubbles in tubes. J. Fluid Mech. 10,
166188 (1961).
37. Chen, J. D. Measuring the lm thickness surrounding a bubble inside a
capillary. J. Colloid Interface Sci. 109, 341349 (1986).
38. Chaudhury, K., Acharya, P. V. & Chakraborty, S. Inuence of disjoining
pressure on the dynamics of steadily moving long bubbles inside narrow
cylindrical capillaries. Phys. Rev. E 89, 053002 (2014).
39. Stein, D., Kruithof, M. & Dekker, C. Surface-charge-governed ion transport in
nanouidic channels. Phys. Rev. Lett. 93, 035901 (2004).
40. Levine, S., Marriott, J. R. & Robinson, K. Theory of electrokinetic ow in a
narrow parallel-plate channel. J. Chem. Soc. Faraday Trans. 71,111 (1975).
41. Kim, J., Song, M. & Kim, J. Zeta potential of nanobubbles generated by
ultrasonication in aqueous alkyl polyglycoside solutions. J. Colloid Interface
Sci. 223, 285291 (2000).
42. Cho, S. H., Kim, J. Y., Chun, J. H. & Kim, J. D. Ultrasonic formation of
nanobubbles and their zeta-potentials in aqueous electrolyte and surfactant
solutions. Colloids Surf. A 269,2834 (2005).
43. Fan, X., Zhang, Z., Li, G. & Rowson, N. A. Attachment of solid particles to air
bubbles in surfactant-free aqueous solutions. Chem. Eng. Sci. 59, 26392645
(2004).
44. Behrens, S. H. & Grier, D. G. The charge of glass and silica surfaces. J. Phys.
Chem. 115, 67166721 (2001).
45. Bhakta, A. & Ruckenstein, E. Decay of standing foams: drainage, coalescence
and collapse. Adv. Colloid Interface Sci. 70,1124 (1997).
46. Scales, P. J., Grieser, F., Healy, T. W., White, L. R. & Chan, D. Y.
Electrokinetics of the silica-solution interface: a at plate streaming potential
study. Langmuir 8, 965974 (1992).
47. Pu, Q., Yun, J., Temkin, H. & Liu, S. Ion-enrichment and ion-depletion effect
of nanochannel structures. Nano Lett. 4, 10991103 (2004).
48. Kwak, R., Kim, S. J. & Han, J. Continuous-ow biomolecule and cell
concentrator by ion concentration polarization. Anal. Chem. 83, 73487355
(2011).
49. Ko, S. H. et al. Nanouidic preconcentration device in a straight microchannel
using ion concentration polarization. Lab Chip 12, 44724482 (2012).
50. Song, L., Hennink, E. J., Young, I. T. & Tanke, H. J. Photobleaching kinetics of
uorescein in quantitative uorescence microscopy. Biophys. J. 68, 25882600
(1995).
51. Schoch, R. B., Cheow, L. F. & Han, J. Electrical detection of fast reaction
kinetics in nanochannels with an induced ow. Nano Lett. 7, 38953900
(2007).
52. Durand, N. F. Y. & Renaud, P. Label-free determination of proteinsurface
interaction kinetics by ionic conductance inside a nanochannel. Lab Chip 9,
319324 (2009).
53. Duan, C. et al. Label-free electrical detection of enzymatic reactions in
nanochannels. ACS Nano 10, 74767484 (2016).
54. Duan, X. et al. Functionalized polyelectrolytes assembling on nanoBioFETs
for biosensing applications. Adv. Funct. Mater. 25, 22792286 (2015).
55. Han, Z., Wang, Y. & Duan, X. Biofunctional polyelectrolytes assembling on
biosensorsa versatile surface coating method for protein detections. Anal.
Chim. Acta 964, 170177 (2017).
56. Stubenrauch, C. & von Klitzing, R. Disjoining pressure in thin liquid foam and
emulsion lms - new concepts and perspectives. J. Phys. Condens. Matter 15,
R1197 (2003).
57. Derjaguin, B. V. & Churaev, N. V. Structural component of disjoining
pressure. J. Colloid Interface Sci. 49, 249255 (1974).
58. Bocquet, L. & Charlaix, E. Nanouidics, from bulk to interfaces. Chem. Soc.
Rev. 39, 10731095 (2010).
Acknowledgements
We acknowledge the nancial support from NSCF (Grant Nos. U1732143 and
U1730133), Fundamental Research Funds for the Central Universities (Grant Nos.
3102017jc01001, 3102019ghxm020, and 3102019PB006), and the support from Analy-
tical and Testing center of Northwestern Polytechnical University in Xian.
Author contributions
Y.X. conceived and designed the experiments. Y.M. and M.S. performed the experiments.
X.D. provided the biomolecule sample and operated the modication of biomolecule. Y.X
and Y.M. set up the theoretical model and analyzed the data. Y.X., Y.M., J.E., and A.vdB.
wrote the manuscript. All authors actively took part in all scientic discussions.
Competing interests
The authors declare no competing interests.
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... Inherent to these models is the assumption that the overall conductance of a nanochannel-microchannel system ( Fig. 1) is determined solely by the nanochannel resistance. Since both models are remarkably simple and intuitive, they have not been challenged nor scrutinized, and as such are still in use [14,33,34,36,[38][39][40][41][42][44][45][46]49]. ...
... In contrast to the previous "saturation-to-linear-increase" paradigm, which neglected the effects of the microchannels, the recent approach emphasizes the importance of the microchannels and shows that theσ ∼c 0 scaling originates due to microchannel effects. Since the Ohmic response lays at the heart of any nanofluidic based application (electrodialysis [55][56][57][58][59], energy harvesting [3,[34][35][36][37][38]51,[60][61][62], fluid-based electrical diodes [4,51,[63][64][65][66][67], DNA biosensors [68][69][70][71][72][73][74][75], biomaterial modeling [33], and modeling basic physiological phenomena [76]) that span all nanoporous material (grapheneoxide-based membranes [5,14,[25][26][27]40,77], carbon nanotubes [20,78,79], silicon nanochannels and nanopores [6,39,46,52,80,81], conducting hydrogels [33], colloidbased membranes [7,8,41], mesoporous silica films [28], exfoliated layers of a clay mineral [29], Nafion [82], cellulose nanofiber membrane from wood [30,42], Ti 3 C 2 MXene membranes [9,35,36], MXene/Kevlar membranes [34], single-layer MoS 2 nanopores [18], AMX-Sb anion exchange membranes [83][84][85], and more [38,43,44]), it is crucial to revisit the nanochannel conductance "saturationto-linear-increase" paradigm suggested two decades ago and reconcile the apparent inconsistency between the original "saturation-to-linear-increase" paradigm to the (a) (c) ...
... On the one hand, there is abundant evidence supporting the older paradigm (see all of the above-mentioned works, notably recent works [14,33,34,36,[38][39][40][41][42][44][45][46]49]). As with any well-established paradigm it is difficult to question and/or challenge it. ...
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... On the one hand, there is abundant evidence supporting the older paradigm (see all of the above-mentioned works, notably recent works [14,33,34,36,[38][39][40][41][42][44][45][46]49]). As with any well-established paradigm it is difficult to question and/or challenge it. ...
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We found that gold nanoparticles, when heated to close to their melting point on substrates of amorphous SiO2 or amorphous Si3N4, move perpendicularly into the substrate. Dependent on applied temperatures, particles can become buried or leave nanopores of extreme aspect ratio (diameter ≅ 25 nm, length up to 800 nm). The process can be understood as driven by gold evaporation and controlled by capillary forces and can be controlled by temperature programming and substrate choice.Keywords: Nanopore; silicon oxide; silicon nitride; gold; dewetting; surface energy