Nano-copper Enhanced Flexible Device for Simultaneous Measurement of Human Cardio-pulmonary Activities

Background: Cardiopulmonary activities re�ect the ability of the human heart to pump blood and the lungs to inhale oxygen. Thus, a device could simultaneously measure electro-cardiac signal and respiratory pressure could provide vital signs for predicting early warning of cardio-pulmonary function-related chronic diseases such as cardiovascular disease, and respiratory system disease. Results: In this study, a �exible device integrated with piezo-resistive sensing element and voltage-sensing element was developed to simultaneously measure human respiration and electro-cardiac signal (including respiratory pressure, respiration frequency, and respiration rhythm; electro-cardio frequency, electro-cardio amplitude, and electro-cardio rhythm). When applied to the measurement of respiratory pressure, the piezo-resistive performance of the device was enhanced by nano-copper modi�cation, which detection limitation of pressure can reduce to 100 Pa and the sensitivity of pressure can achieve to 0.053 ± 0.00079 kPa -1 . In addition, the signal-to-noise ratio during bio-electrical measurement was increased to 10.7 ± 1.4, �ve times better than that of the non-modied device. Conclusion: This paper presents a �exible device for the simultaneous detection of human respiration and cardiac electrical activity. To avoid interference between the two signals, the layout of the electrode and the strain sensor was optimized by FEA simulation analysis. To improve the piezo-resistive sensitivity and bio-electric capturing capability of the device, a feather-shaped nano-copper was modi�ed onto the surface of carbon �ber. The operation simplicity, compact size, and portability of the device open up new possibilities for multi-parameter monitoring.


Background
Ischaemic heart disease and stroke have been the top killer diseases in the world.According to the health data from American Heart Association in 2019, more than 33% of deaths worldwide were related to heart diseases [1,2], a great number of which are related to cardio-pulmonary dysfunction [3].It has been proved that continuous and simultaneous monitoring of physiological signals, including electro-cardiac signals (like beating frequency, beating rhythm and electrical pulse) and respiratory signals (like respiratory pressure, respiration frequency, and respiration rhythm), would be bene cial in early prediction and diagnosis of these diseases [4,5], because this can help patients to get timely treatment, and lower the death rate and the caring costs.
A number of devices have been conducted to record electro-cardiac signals and human respiration [6][7][8][9][10][11][12][13][14][15].Electrocardiograph (ECG) was commonly used to describe the electrical activity of the heart.abnormal information of heart frequency and heart rhythm can be detected from ECG waveforms (e.g.P wave and QRS complex), which can be further interpreted for diagnosis of heart diseases (e.g.myocardial ischemia, myocardial infarction) [9,[16][17][18].Conventional 12-lead ECG could provide comprehensive heart condition.However, the large size and the large bundle of cables make ECG only suitable for hospitalspeci c examinations but not for long-term and continuous monitoring of heart status [8,19].The early warning signals of random heart abnormality due to lacking much necessary context to the data could be missed [20].A exible micro/nano device is a powerful tool to solve this problem.For example, a graphene-based dry exible electrode was used for a-week continuous recording ECG without degradation in the signal quality [15,21].
For measurement of respiration, either pressure / strain sensing or air ow sensing methods were applied to detect respiratory info (including respiratory frequency respiratory rhythm, and respiratory pressure / volume) in recent proposed devices [8,[22][23][24][25].However, air ow sensors need to be worn over face, which discouraged patients from long-term respiratory monitoring.The strain-depended respiratory devices were commonly attached to the surface of human chest, which could also sense other bioelectrical signals due to the co-existing physiological signals in the same region and the conductive materials used in the device (e.g.nano-gold or carbon-based nanomaterials) [26][27][28][29][30].To achieve monitoring the simultaneous signals of ECG and respiration, a key technology is signal processing to separate respiratory and heat signals, using such as wavelet signal processing or principal component analysis, which have already been investigated extensively [12,38,39].However, the signal processing method only provides an indicator (e.g.normalized parameter) but not a physical quantity (e.g.pressure or air in ow) for evaluating respiration, direct correlations between the indicator and the respiratory pressure produced by the lung remain to be solved.In addition, signal processing method indeed could separate respiratory signals (0.13 Hz ~ 0.33 Hz) from ECG (1.0 Hz ~ 1.67 Hz) and other bio-signals (e.g.haemo-dynamic uctuations: 0.04 Hz ~ 0.09 Hz) in human normal activity [40].However, this method cannot distinguish the respiratory signal in abnormal state.For example, the respiratory frequency was less than 0.1 Hz when intracranial hypertension occurred [41]; another, respiratory frequency was higher than 3.0 Hz when psychopathology of hysteria occurred [42].Furthermore, some other devices reported simultaneously measurement of respiratory signals and ECG [22].For example, a polyvinylidene-uoride polymer sensor patch based on the piezoelectric mechanism was developed for simultaneously monitoring heartbeat and respiration [8].However, the devices also used an indicator to replace the physical quantity (pressure or air in ow) (Table 1), which is a similar issue with the signal processing method.
In this study, we proposed a exible device that can simultaneously measure ECG and respiration (including parameters of electro-cardio frequency, electro-cardio rhythm, and electro-cardio amplitude; respiratory frequency, respiratory stress, and respiratory rhythm).Nanoparticle modi cation and nite element analysis (FEA) were used to improve the performance of sensing elements and optimize the structure of devices [43].The key improvement of the device is that the carbon ber was modi ed with nano-copper.The modi cation of nano-copper onto electrochemical methods has excellent performance in improving the sensitivity and the detection limit of the analyte [44][45][46].However, the piezo-resistive sensitivity and of electrical capturing ability of the nano-copper have not been reported.Finite element analysis (FEA) was used to optimize the structure of device.For the devices with monitoring functions of respiration and ECG, FEA optimized the layout of each sensing element from the following considerations [47]: (1) The microelectrode for measuring ECG should locate at the place with small strain, which can avoid the movement of microelectrode during breath [48].
(2) In addition, the distance between the electrode and the piezoresistive strain sensor should be determined.This can reduce the effect of the transient electrical eld on detecting resistance signals during the electrical pulse generated by the heart [49].To obtain stabilized output, the device was preconditioned for 4500s.The relationship between the resistance change and the pressure was also calibrated, which would be used for converting the resistance change in the measurement to the pressure of human respiration.Finally, 17 volunteers were tested to prove the suitability of the device for simultaneously monitoring of ECG and respiration.

Results And Discussions
2.1 CNT-PDMS device characterization.

FEA result of the exible device
The simulation of the stress distribution and the simulation of the electric eld distribution were used to guide the layout of the exible device.
For mechanical stress simulation, a pressure (1.5 kPa) was applied onto the whole device.The edges of the device were set as xed, and the other parts of the device were set as free.The young's modulus of the oating PDMS membrane was 467.5 kPa ± 10.27 kPa measured by AFM.The simulation result (Fig. 1A) showed that the stress gradually decreased from the center of the device along the radial direction, and stress concentration occurred at the xed edges of the device.The corresponding stress values decreasing from 0.51 kPa to 0.06 kPa.The results also revealed that the layout of the electrodes for ECG should avoid the locations of the stress concentration and the center of the device.This arrangement could reduce the in uence in detecting ECG caused by the shape change of the device during the movement.
As resistance change was performed for detecting human respiration, a continuous voltage (0.5V) was applied to the strain sensor.The electrical eld generated by the applied voltage may interfere with cardiac electrical pulse detection.Based on the consideration, an insulating layer was added between the microelectrode and the strain sensor.To prove the e ciency of the insulating layer, the electrical eld of the device with and without insulating layer was simulated (Fig. 1B).The top inset in Fig. 1B is the electrical eld distribution of the device without insulating layer.The result showed that (1) the electrical eld could transport across the whole device, thus it could interfere with the detection of the cardiac electrical pulse.(2) The electrical eld covered all the top layers of PDMS, and electrical eld unevenly decreased from the positive pole (4.5 V/m) to the grounding pole (0 V/m).However, the bottom inset in Fig. 1B showed that electrical eld only exists along the strain sensor.The electric eld strength of other locations, especially around the microelectrodes were nearly 0 V/m after adding an insulating layer.

Device characterization
To characterize the geometry of the device, an optical pro ler (Bruker, USA) was employed to scan the top-surface morphology during steps of fabrication.The thin PDMS lm was the critical component in the device, which thickness determines the performance in sensing the strain caused by respiration.To make the rst layer of PDMS lm with a thickness of 30 μm, the PDMS was spin-coated onto photoresist (AZ4620) at the speed of 1600 r/min as shown in the left-rst plot of the Fig. 1D.After locating carbon ber into photoresist, the thickness of the device increased to 37 μm, as shown in the left-second plot of Fig. 1D.
Then, the thickness of the second PDMS layer was spin-coated at the above same speed, which was around 30 μm.The total thickness of the device was around 67 μm after locating ECG electrode.
XRD was used to determine the existence of nano-copper and carbon ber, which is the direct evidence for the periodic atomic structure of a speci c element[61].An inner-section of a exible device was identi ed by XRD with scan the 2θ degree from 10°t o 85° (Fig. 1G).The spike at the 2θ degrees of 42.5°, 51°, 45°, and 73° represent the existence of nano-copper.Similarly, the spike at the 2θ degree of 22 was the characteristic peaks of carbon ber.The results demonstrate that the nano-copper was modi ed on the surface of carbon ber.
Then, the 2D surface morphology of carbon bers with and without nano-copper was captured by SEM (Fig. 1H to Fig. 1K).
Fig. 1H shows that it displays like a cylindrical stick with a diameter of 7.1 μm ± 0.2 μm.Fig. 1I shows that the tidy and smooth surface of carbon ber, which is a bene t for nano-copper to adhere.For the carbon ber modi ed with nano-copper (Fig. 1J), the diameter increased to 8.0 μm ± 0.2 μm, and the enlarged SEM (Fig. 1K) shows that numbers of feather-shaped nano-copper are grown on the surface of carbon ber.The inset in Fig. 1K shows that the feather-shape nano-copper consists of numbers of spherical nanoparticles, which diameter concentrates at 100 nm.These nanoparticles can greatly improve the speci c surface area of the sensor, which can improve the sensitivity of the sensor and lower detection limit [62].

Mechanical behaviors of the exible device 2.2.1 Improvement of mechanical response after exible device modi ed with nano-copper
To compare the mechanical behaviors between the exible device with nano-copper and the device without nano-copper, the strain testing was rst performed.Fig. 2A shows the resistances of the devices with and without nano-copper changed with a gradual increase of strain.The resistances of both devices increase with each 2.5% increment of the strain.Under the same strain, the resistance response (ΔR/R 0 ) of the exible device with nano-copper was around 12-fold than that of the exible device without nano-copper.For example, the resistance response (ΔR/R 0 ) of the exible device without nano-copper was 0.0011 under the strain of 10%, whereas ΔR/R 0 of the exible device with nano-copper was 0.013.Furthermore, the strain-resistance curve was tted, Fig. 2 B shows the linear range of the modi ed exible device is from 7.5% to 30%.However, the linear range of the exible device without nano-copper was from 10% to 22%.The results revealed that the mechanical response (strain sensitivity and linear range) of the device could improve through modifying nano-copper.

Tensile failure and response time of the device with and without nano-copper
Both devices were broken when the strain increased to around 32.5%, this result was similar to the breaking point of PDMS without carbon ber [63].This indicates that PDMS embedded with individual carbon ber (diameter = 7 μm) would not affect the tensile performance of exible devices.
In addition, we found that the exible device with nano-copper would prolong the response time to stabilize resistance for each strain change.For example, when the strain of the thin PDMS membrane is greater than 10%, the stable time of exible device with nano-copper needs more than 20 s.However, the response time of a exible device without nano-copper needs no more than 10 s.This result may be attributed that many nano-copper nanoparticles overlapped on the surface of carbon ber (veri ed from the SEM in Fig. 1K) of nano-copper, which is not stable when the device undergoes strain.To overcome the issue, preconditioning for each fresh fabricated device would be performed as follows.

Preconditioning strain sensor
To stabilize the resistance of the modi ed exible device within the measurement period (human respiration period is around 4 s ~ 6 s), each fresh device was rstly preconditioned for 4500 s under the strain of 7.5%.Fig. S2A showed that resistance of exible devices with nano-copper changed over time similarly in logarithmic growth way.The resistance increased from 7.96 kΩ to 10.82 kΩ.The P-value between (ΔR/R 0 ) at 4500 s and that at 5500 s was 0.13 (n=4), which indicates that the response of device with nano-copper would be stable after preconditioning 4500 s.

Calibrating Relationship between respiratory pressure and ΔR/R 0
For quantifying respiratory stress using the developed device, the relationship between resistance change (ΔR/R 0 ) and corresponding stress caused by respiration was necessary to be established [64].To this end, a device was assembled onto the surface of an open cylinder (Fig. S2B), thin-lm in the device would bulge / concave when the air was imported/exported with a micro-pump.The electrical resistance of carbon ber would change due to the shape change (strain change) of the thin lm [55].
Fig. 2C showed that their electrical resistance stepped increased when pressure changed from 100 Pa to 0.6 kPa.The signal-tonoise ratio between resistance and background noise was larger than three when 100 Pa was applied, which was regarded as the detection limit of the strain sensor.Fig. 2E was the enlarged plots of resistance response and the input pressure when the pressure changed from 0.35 kPa to 0.40 kPa.For obtaining a steady piezo-resistive response, each pressure was recycled 30 times.The data was extracted and tted as shown in Fig. 2G.The calculated sensitivity of the device was 0.053 ± 0.00079 kPa -1   with a tting coe cient of 0.96.The ability of store charge of the microelectrodes in the device plays an important role in sensing the weak ECG [18].To test this ability, electrochemical method (Differential pulse voltammetry, DPV) was used.The microelectrodes were scanned from -0.3 V to 0.3 V at the speed of 50 mV/s in the 0.05 M solution of potassium ferricyanide (K 3 Fe(CN) 6 ), as shown in Fig. 2F.The area of the CV curve represents the charging-discharging performance.The area of microelectrode with nano-copper was 6.6 times larger than that of microelectrode without nano-copper (8.0 nA v.s.1.2 nA).This demonstrates that the ability of store charge would largely increase by modi cation of nano-copper.This is due to that many porous nanoparticles increase speci c surface area and increase electron transfer speed [65].

Anti-background noise ability
Electrical background noise is another factor that would affect the detection of ECG [66].The reported amplitude of ECG often ranges from 0.1 mV to 10 mV.If the introduced background noise was larger than this value, the device will not observe the effective ECG signal [67].To this end, we performed anti-noise testing.Fig. S2 E showed the time domain graph of the introduced background noise.The amplitude of the microelectrode without nano-copper was 3.45 ±0.68 mV, however, the amplitude of the microelectrode with nano-copper was 0.37 ± 0.09 mV.In the meanwhile, 50Hz power line was the primary interference from spectral analysis (Fig. 2I).This is because that the nano-copper carries with numbers of charged active-particles on the surface, which can increase the electron transfer speed and improve the anti-interference performance [59].and the conductive path formed by the inter-connections of nano-copper.When an external force or pressure is applied on the nano-copper, the distance between the adjacent nano-copper becomes larger, the formed nano-copper conductive path can be broken, which was similar to the composites of CNT and PDMS [68][69][70].Accordingly, the chance of electronic transition between adjacent nano-copper is reduced.The morphologies of nano-copper under the different electroplating time were captured by SEM to explore the strain-sensing mechanism.(Fig. 3C-F and Fig. 3H).Only a few nano-copper was modi ed on the surface of carbon ber when electroplating time was 5s.With the increase of electroplating time, the surface of nano-copper was gradually covered.Until the electroplating time was 80s, a uniform layer of nano-copper was grown on the surface of carbon ber.
However, the blocky-shaped particles appeared and irregular surface lead to an increase of roughness when the electroplating time increased to 160s.

Optimization and voltage -sensing mechanism of the ECG electrode
To obtain the voltage signal with anti-noise ability, the modi cation time for the ECG electrode was also explored.Signal-tonoise-ratio (S/N) was used to evaluate the performance of each electrode under different conditions.The curve in Fig. 3B showed that S/N increased with the increase of electroplating time.When electroplating time was 40s, the S/N trends to be steady with the value of 10.7 ± 1.4, which has no signi cant difference with the S/N observed under modi cation time of 80s and 160s.Thus, 40s were selected as the modi ed condition for micro-electrode.
To explore the mechanism of sensing ECG, an equivalent circuit model between the microelectrode and the surface of the skin was proposed.As the physiology of pigskin resembles human skin [71], it was used to simulate human skin (a exible device was located onto the surface of pigskin, Fig. 3G).The frequency responses (Bode plots and Nyquist plots) of pigskin, microelectrode, and the integrity of the pigskin and microelectrode were respectively measured from 0.01 Hz to 100 kHz (at 20 mV), which were shown in Fig. 3J and Fig. 3 K.Bode plot of carbon ber (blue curve in Fig. 3J) showed that carbon ber is a resistance with the value of 10.87 kΩ that will not change with frequency change.The Nyquist plot (red curve in Fig. 3E and F) shows that frequency response of pigskin is a straight line with slope of 0.45, which demonstrates that pigskin behaves as a constant phase element.The Nyquist plot of the black curve in Fig. 3F shows that a semi-circle appears when the carbon ber electrode attaches to the surface of pigskin, which corresponds to the gap between exible device and pig skin (the inset in Fig. 3I).It can be regarded as the parallel of the resistance and capacitance in the circuit model, and the value of capacitance is 1.6 μF ± 0.41 μF (Fig. 3I).

Simultaneous measurement of respiration and electrical activity from the human body
To further verify the ability of our device that can measure respiration and electrical activity, 17 volunteers were employed to simultaneously record breath and heart electrical activity before and after exercise.The volunteers' age ranged from 18 to 31, with a height from 55 kg to 75 kg.Supplementary video 2 and Fig. 4A showed that a volunteer was monitored by our developed exible device, the rhythmical ECG and resistance signals can be simultaneously observed at resting state.The top-left plot in Fig. 4B shows that the ECG signal sample was recorded from a volunteer at the resting state by a carbon ber modi ed with nano-copper.The top-right plot in Fig. 4B shows that the same carbon ber was recorded ECG from the volunteer after jumping 50 times.We also used the carbon ber without nano-copper to measure ECG signal from the volunteer (see the bottom-plots in Fig. 4B).To quantify the difference of ECG signals observed from two kinds of carbon ber, statistics for the signal-to-ratio (S/N) was proceeded (Fig. 4C).At resting state, the S/N of the microelectrode with nano-copper was 10.7±1.4,and the S/N of the bare microelectrode was 2.2±1.9.The P-value was 0.007, demonstrating that signi cant difference exists between the two kinds of carbon ber.After exercise, Both S/N increased by 486%, but signi cant difference still exists (P-value = 0.01).To clearly characterize the heart state change before and after exercise, Poincaré plot was introduced.Poincaré plot was described by neighboring beating periods, thus it can re ect whether the heart has rhythmic beating.From Fig. 4D, we can see that the beating period gather together about 0.63s at the resting state, after exercise, the beating period shortened to 0.45s and arrhythmic beating occurred in this volunteer.
In addition, respiratory signals were also analyzed.The parameters including respiratory frequency, respiratory pattern, and respiratory stress were quantitatively analyzed [72].At resting state, the respiratory frequency was 0.13 Hz, respiration pattern displays as an asymmetrical triangular wave.Respiratory stress changed from 0.46 kPa to 0.57 kPa.As a comparison, carbon ber without nano-copper was also employed to measure respiration [25].This kind of carbon ber could capture the respiration at the resting state and after exercise.However, the amplitude was much less than that observed from the carbon ber with nano-copper (0.21 kPa vs. 0.57 kPa).Similarly, S/N was also less than that of the electrode with nano-copper (7.3 vs.10.2).We used Fourier transform to compare the energy distribution with and without nano-copper (Fig. 4F).At resting state, the power magnitude of the respiratory signal measured by nano-copper modi ed electrode was 5.20 x10 -5 Ω, whereas the magnitude of the respiratory signal measured by bare electrode was 1.01 x 10 -8 Ω.After exercise, the magnitude of respiratory signal measured by nano-copper modi ed electrode was 3.18 x 10 -4 Ω, the magnitude of respiratory signal measured by bare electrode was 7.44 x 10 -6 Ω.Furthermore, we analyzed four of 17 volunteer's respiratory frequency and respiratory stress using box plot (Fig. 4G and   H).For respiratory frequency, the four volunteers have obvious difference before and after exercise, with the range changing from 0.12 ± 0.11 Hz to 0.38 ± 0.14 Hz.Respiratory stress represents the strain change of exible device caused by the inspiratory volume of air.Thus, we compared the four volunteer's respiratory stress before and after exercise.All amplitude of respiratory stress decreased after exercise, which speci c values of respiratory stress changed from 0.55 ± 0.09 kPa to 0.28 ± 0.12 kPa.

Simulation of Strain distribution and electric eld intensity
Finite element analysis (FEA) was employed to optimize the structure of a exible device [50].The simulation result would contribute to optimizing the layout of sensing elements (microelectrode and strain sensor) in exible devices.The elastic modulus of the exible device, dimensions of the device and applied pressure were used as input data for the FEA model.The elastic modulus of the exible device was 467.5 ± 10.27 kPa (n = 6), which was measured by Atomic Force Microscopy (AFM, Bruker, America) (Fig. S1A).PDMS was often regarded as the isotropic elastic materials in exible device, and which Poisson's ratios was 0.49 in simulation model [51].Optical pro ler (Bruker, USA).The applied pressure was 1.5 kPa, which was measured from a volunteer using a pressure meter.
To determine whether the applied voltage in the strain sensor affects the detection of heart electrical signals, the distribution of electric eld was simulated.A 2-Dimensional axisymmetric geometry was used as the simpli ed model.The material of exible device is selected as PDMS, and its conductivity was de ned as 10 − 3 S/m.The conductivity of the electrode with nano-copper is de ned as 10 6 S/m, which relative dielectric constant is 12.The remaining parameters are processed by the default values of the material properties in the software [52].

Fabrication of the exible device
The developed device could simultaneously sense electrical pulse and strain change, which is achieved by the microelectrode and piezo-resistive element [50].Figure 1C shows the fabrication process: Acrylic slide with thickness 2 mm was selected as a substrate, and it was washed following acetone, ethyl alcohol, and deionized water.Then, we calibrated the relationship between the lm's thickness and spin-coating speed.As the viscosities of PDMS and photoresist (AZ4620) are different, Fig. S1C and D showed their thickness decreased with exponential decay.When the spin-coating speed was 400r/min, AZ4620 would have a thickness of 30 µm; when PDMS was spin-coated with speed of 1600 r/min, the lm thickness was around 30 µm.Through these relationships, the exible device was fabricated according to the process in Fig. 1C.The results are similar to the reference [53].A mask with a spiral pattern was placed onto the photoresist and was exposed to UV light (wavelength: 365 nm) for 23 s using a lithography machine.After that, the spiral channel was patterned in the layer of photoresist, the carbon bers (the nanocopper modi ed or the unmodi ed) were gently embedded into the channels.After that, polydimethylsiloxane (PDMS, Sylgard 184, Dow Corning, US) with a weight ratio of 1:10 (curing agent to prepolymer) was spin-coated for 1 min, and it was baked in the oven at 65° for 40 min [54].When PDMS was half-solidi ed, the carbon bers modi ed with copper nanoparticles were assembled to the surface of PDMS layer.At each end of carbon ber, the copper wire was weld by an electric iron.After that, the curing process was continued by baking for 4 hours.Finally, the device with PDMS was immersed in the acetone for dissolving AZ4620, a exible device with microelectrodes and strain sensors was fabricated as shown in Fig. 1G.

Electrochemical synthesized copper nanoparticles
The electrochemical modi cation of copper nanoparticle was performed as follows [55].In a typical procedure, carbon ber was rstly washed by oxygen plasma for 15 s at the power of 50 W.Then, 0.5 g copper sulfate (CuSO 4 ) was dissolved in 100 mL 0.1M solution of sodium nitrate (NaNO 3 ).Carbon ber, platinum, and Ag/AgCl were respectively used for a working electrode, a counter electrode, and a reference electrode.The electrodeposition was carried out by chronoamperometry for 50 s at the voltage of 12 V at room temperature.To obtain the uniform copper nanoparticle on the surface of carbon ber, the carbon ber was slowly inserted into the reaction chamber with a xed speed of 5 mm/s[56].After that, the modi ed carbon ber was assembled into the PDMS.

Characterization of the exible device
Optical pro ler (Bruker, USA), SEM (Hitachi, Japan), AFM (Bruker, USA), and XRD (Rigaku, Japan) were employed to characterize exible devices.The optical pro ler was used to obtain geometric dimensions of the device during fabrication.In each step of fabrication, the thickness and width of the device were investigated, and which would contribute to constructing a geometry model used in the simulation.Before fabricating device, the thickness of the PDMS was also measured by optical pro ler for correlating with spin-coating speed [57].Atomic Force Microscope (AFM) and SEM were used for observing 2D and 3D surface  Tensile failure is the maximum tensile stress that a device can take.The test was performed to the exible device embedded with nano-copper modi ed carbon ber and the device with unmodi ed-carbon ber.First, both ends of the exible device were xed into two PDMS blocks (the inset in Fig. 2A).Then, a home-made stretching instrument (Fig. S1B and supplementary information video 1) closely clamps PDMS blocks and stretches them gradually.In each step, the stretching instrument increases 2.5% strain through programmable procedure, and keep it at least 120 s for obtaining the stable resistance.The changes in strain and resistance were recorded until the exible device broke down.To obtain the stable resistance-response for strain change, we performed preconditioning (tensile training) for each device (including the carbon ber modi ed with nanocopper and the bare carbon ber).Through analyzing the curves between strain and resistance, the rst point in the linear range of the curve was selected for tensile training.The resistance was continuously recorded until the stable response of the strain sensor was observed.The sampling rate was 100 Hz.For each device, the tensile training was performed along portrait orientation and landscape orientation.

Calibration of the exible device
To predict the pressure generated by respiration, the relationship between pressure and resistance should be calibrated.We sealed a device onto the surface of a cavity and inserted a needle into the cavity from side face.A homemade microinjection pump was used to bulge the exible device, and a Y-type tee was connected with pressure meter (accuracy = 1 Pa, Hong Kong) (A schematic was shown in Fig. S2B).The resistance change and pressure were simultaneously recorded during exible device were bulged by the pump.The input pressure changed from 100 Pa to 600 Pa and kept for 2 min at each pressure.The sampling rate was 100 Hz.The bulged shape of exible device was also captured by microscopy at different pressure (Fig. S2D).

Anti-noise ability and bandwidth of the microelectrode in the exible device
To evaluate the anti-noise ability of microelectrode in a exible device, the introduced electrical noise testing was performed [59].
The microelectrodes (carbon ber with nano-copper and the bare carbon ber) were respectively connected to an amplifying circuit, voltage signal was recorded with time-varying at a sampling frequency of 10 kHz.Anti-noise comparison of the two-type microelectrodes was analyzed by the magnitude and power spectrum of the induced voltage.
To verify whether the bandwidth of the device is enough for capturing respiration and electrical activity of the heart, impedance spectroscopy analysis (Autolab, Switzerland) was used to scan a device from the frequency of 0.1 Hz to 100 kHz.The magnitude of AC voltage was set as 20 mV[60].

Simultaneous detection of respiration and ECG in the human body
Flexible devices were attached to 17 volunteers, whose ECG and resistance change deduced by respiration and heart electrical activity were both recorded.The signals from volunteers at rest were recorded for 2 min, and continuing to record for 2 min after running.We ethically obligated to perform every test.

optimization of nano-copper modi cation
To obtain the optimal sensitivity for the strain sensor and the electrode in the exible device, devices were modi ed for six groups of conditions (5 s, 10 s, 20 s, 40 s, 80 s, and 160 s) at the potential of 12 V.After modi cation, resistance changes of different devices were compared to nd the largest value and its corresponding modi cation condition was selected for the strain sensor in exible device.For microelectrode, the optimal modi cation condition was evaluated by the introduced electrical noise level.

Conclusion
This paper presents a exible device for the simultaneous detection of human respiration and cardiac electrical activity.To avoid interference between the two signals, the layout of the electrode and the strain sensor was optimized by FEA simulation analysis.To improve the piezo-resistive sensitivity and bio-electric capturing capability of the device, a feather-shaped nanocopper was modi ed onto the surface of carbon ber.The piezo-resistive strain sensor in the device achieved the resolution of 100 Pa in pressure measurement with a sensitivity of 0.053 ± 0.00079 kPa − 1 , The S/N ratio of the voltage improves from 2.2 ± 1.9 to 10.7 ± 1.4.Furthermore, the optimal modi cation condition and mechanisms of sensing strain and voltage were determined.Finally, the device was applied to measure the signals of 17 volunteers.In future work, we will integrate the signal acquisition and wireless transmission elements in our device.

2. 4
Electrical performance of the modi ed carbon ber 2.4.1 Stored charge capacity of the electrode in exible device

2. 5
Optimization of modi cation time and exploring mechanisms for sensing strain and voltage 2.5.1 Optimization and strain-sensing mechanism of the strain sensor To enable the strain sensor and the ECG electrode of the device with the optimized performance, the modi cation time of the nano-copper was explored.Six groups of modi cation time (5 s, 10 s, 20 s, 40 s, 80 s, and 160 s) were used.Resistance changes (ΔR/R 0 ) of the modi ed devices were measured under the pressure change of 0.51 kPa.Fig.3Ashows that ΔR/R 0 achieved to the largest value (0.023) at the modi cation time of 80 s, then ΔR/R 0 decreased with the increase of modi cation time.The resistance change of carbon ber with nano-copper is determined by the distance between adjacent nano-copper nanoparticles morphologies of individual particles and groups of particles.AFM offers the visualization in diameters of nanoparticles.X-ray Powder Diffraction (XRD) (Rigaku, model Geiger ex) was used for phase identi cation of PDMS, carbon ber and nano-copper and can provide information for determining the existence of the three materials.The diffractograms were measured at a scanning speed of 8°/min, by means of a tube voltage of 40 kV and a tube current of 30 mA[58].

3. 5
Tensile failure test and preconditioning of exible device

Simulations
for guiding the layout of the exible device and characterization of the fabricated device.(A) Stress simulation of and strain sensor in the exible device.The stress gradually decreased from the center of the device along the radial direction, and stress concentration occurred at the xed edges of the device.(B) The electrical eld simulation of the electrode in the device with and without insulating layer.The up-top inset revealed that the electrical eld could transport across the whole device.The bottom inset showed that electrical eld only exists along the strain sensor.The electric eld strength of other locations, especially around the microelectrodes were nearly 0 V/m after adding an insulating layer.(C) The fabrication process of exible device.First a thin PDMS lm was spin-coated onto a 2 cm x 2 cm acrylic slide.Then lithography was employed to form a spiral channel and carbon ber was assembled into the channel.The isolation layer was spin-coated onto the carbon ber.Finally, carbon ber adhered to the top layer of PDMS.(D) Determination of exible device dimension during its fabrication.(E) The schematic for the developed device.(F) An image of the fabricated exible device.(G) XRD for determining the existing of carbon ber and nano-copper.(H) SEM of bare carbon ber.(I) SEM of enlarged bare carbon ber for showing its smooth surface.(J) SEM of and the carbon ber modi ed with nano-copper (electroplating time = 80 s).(K) SEM of enlarged carbon ber modi ed with nano-copper, which showing nano-copper with feather-shape.The inset showed that the feather-shaped nano-copper was constructed by spherical nanoparticles.

Table 1
The property comparisons of the current device and our device