On-site biosignal amplification using a single high-spin conjugated polymer

W4406060737 · 수집 2026-09-26 12:32:49

T11690 Advanced battery technologies research 이차전지

CoT 라벨링

라벨링 전

PDF 파일

자동 다운로드한 PDF PDF 보기

기본 정보

DOI 제목 발행년도 저널 URL 페이지 열기 PDF URL PDF 열기 발행기관 피인용수 라이선스

추가 정보 초록 본문

Article https://doi.org/10.1038/s41467-024-55369-6
# On-site biosignal amplification using a single high-spin conjugated polymer

Received: 2 October 2024

Accepted: 5 December 2024

Check for updates

Gao-Yang Ge 1,4, Jingcao Xu 1,4, Xinyue Wang2, Wenxi Sun1, Mo Yang 2, Zi Mei3,
Xin-Yu Deng 1, Peiyun Li1, Xiran Pan1, Jia-Tong Li 1, Xue-Qing Wang1,
Zhi Zhang 1, Shixian Lv1, Xiaochuan Dai 2 & Ting Lei 1

On-site or in-sensor biosignal transduction and amplification can offer several
benefits such as improved signal quality, reduced redundant data transmission, and enhanced system integration. Ambipolar organic electrochemical
transistors (OECTs) are promising for this purpose due to their high transconductance, low operating voltage, biocompatibility, and suitability for
miniaturized amplifier design. However, limitations in material performance
and stability have hindered their application in biosignal amplification. Here,
we propose using high-spin, hydrophilic conjugated polymers and a computational screening approach to address this challenge. We designed a high-spin
polymer, namely P(TII-2FT), which exhibits satisfactory, stable, and balanced
ambipolar OECT performance. The figure-of-merits achieved by the P(TII-2FT)
devices surpass those of the current leading materials by 5 to 20 times,
resulting in remarkable voltage gains while maintaining a compact form factor.
Based on this amplifier, we have successfully achieved on-site capture and
amplification of various electrophysiological signals with greatly enhanced
signal quality.

Biosignal recording systems typically involve front-end signal transducers and downstream backend signal amplification, filtering, or feature
detection components 1 . To mitigate noise, enhance signal quality,
reduce redundant data transmission, and improve system integration,
on-site or in-sensor signal processing has emerged as an increasingly
significant avenue in bioelectronics 2,3 . Coating conducting polymers on
electrodes can reduce interfacial impedance and improve the signal-tonoise ratio (SNR) 4,5 . Nevertheless, this approach lacks on-site amplification, and the large physical distance between the sensors and the
backend signal processors introduces additional noise, resulting in
compromised signal quality 6,7 . To achieve on-site amplification with
compact form factors and exceptional performance, organic electrochemical transistors (OECTs), a burgeoning polymer-based bioelectronic technology 8–10, have garnered growing attention due to their low
operating voltage (<0.8 V), remarkable flexibility/stretchability, high
transconductance (gm), and ability to form intimate biointerface 11 .

OECTs have found utility in diverse biological applications,
including metabolite sensing and electrophysiological recordings,
with performance surpassing those of electrode-based sensors and
inorganic transistors 12,13 . However, their current output presents challenges for practical implementation, given that most electrophysiology equipment demands a voltage input 14 . To tackle this issue,
OECT-based circuits, such as unipolar circuits 15, complementary metaloxide-semiconductor (CMOS)-like circuits 16 and ambipolar OECTbased circuits 14, have been devised (Supplementary Fig. 1). Ambipolar OECT-based circuits can enhance device integration, reduce footprint, and simplify manufacturing processes 14 . Nonetheless, the
performance and stability of ambipolar OECT materials remain
inadequate to meet the requirements of practical signal amplification.
Moreover, achieving in vivo and on-site amplification within living
organisms has yet to be realized, likely due to limitations in device
stability and performance.

1National Key Laboratory of Advanced Micro and Nano Manufacture Technology, School of Materials Science and Engineering, Peking University,
Beijing, China. 2 School of Biomedical Engineering, Tsinghua University, Beijing, China. 3 School and Hospital of Stomatology, Peking University, Beijing, China.
4These authors contributed equally: Gao-Yang Ge, Jingcao Xu. [e-mail: tinglei@pku.edu.cn](mailto:tinglei@pku.edu.cn)

The past few years have witnessed rapid advancements in OECT
materials, with p-type materials showcasing high μC* values exceeding
500 F cm −1 V −1 s −1 and n-type materials demonstrating elevated μC*
values surpassing 50 F cm −1 V −1 s −1 17–20 . In contrast, the current best
ambipolar material is based on blending p-type and n-type materials,
resulting in moderate yet unbalanced performance, with a p-type μC*
of 22.8 F cm −1 V −1 s −1 and an n-type μC* of 11.8 F cm −1 V −1 s −1 21 . Although
this approach is straightforward, it offers limited performance and
may lead to inadequate uniformity in large-area fabrication due to
challenges in controlling the morphology and phase separation of the
two OECT materials. Single-component ambipolar materials are more
appealing, as they simplify device fabrication processes while promoting better film uniformity. However, their performance and stability remain subpar 14,22 . The most promising single-component
ambipolar material, 2DPP-OD-TEG, exhibits a p-type μC* of
31.8 F cm −1 V −1 s −1 and an n-type μC* of 6.8 F cm −1 V −1 s −1, and its device
performance drops rapidly after 84 cycles during p-type operation 22 .
Thus, ambipolar OECT materials are underexplored, significantly
trailing behind their p-type and n-type counterparts. In traditional
OFET material design, achieving high-performance, stable, and
balanced ambipolar characteristics is feasible through the use of
classical low-bandgap donor-acceptor (D-A) polymers 23–25 . Nevertheless, our attempts indicate that this approach is not applicable to
ambipolar OECT materials, primarily due to the challenge of restricted
polaron delocalization and unstable doped states (see Supplementary
Fig. 2 for detailed discussions) 18 . Consequently, the design strategy for
achieving high-performance, stable, and balanced ambipolar OECT
materials remains elusive.

Here, we propose designing high-spin conjugated polymers for
high-performance, stable and balanced ambipolar OECTs. We have
successfully developed a single-component ambipolar polymer, P(TII2FT) (Fig. 1d), which demonstrates balanced and exceptionally high
ambipolar properties with μC* values of 158.6 F cm −1 V −1 s −1 for the
p-type regime and 147.4 F cm −1 V −1 s −1 for the n-type regime. These

values are over 5 to 20 times higher than the current best singlecomponent ambipolar materials. Our ambipolar OECTs also exhibited
unprecedented stability with less than 6% current change after cycling
over 1000 times. Computational studies corroborate that the design of
high-spin polymers facilitates the effective delocalization and stabilization of positive and negative polarons, resulting in enhanced performance and much better stability. By leveraging this material, we
have successfully realized NOT (Inverter), NAND, and NOR gates, as
well as ultrahigh gain amplifiers. Furthermore, we harnessed the
amplifiers to monitor human electrocardiograph (ECG), electroencephalograph (EEG), and mouse electrocorticogram (ECoG) signals.
These biosignals experienced amplification exceeding 70 times,
showcasing the immense potential of employing hydrophilic high-spin
polymers for on-site biosignal capture and amplification.

Results
Polymer design, synthesis, and characterization
Compared with OFET materials, which work in neutral or lightly doped
states, OECT materials generally operate in highly doped states 26, thus
their charge delocalization capabilities and stability in the doped states
are crucial 18 . We propose that a high-performance, stable, and
balanced ambipolar OECT material requires (1) high charge carrier
mobility, (2) stable p-doped and n-doped states and (3) balanced hole/
electron injection/transport ability. To meet these requirements, we
selected polymer building blocks through the following steps: (I) Most
high-mobility conjugated polymers are based on several highperformance building blocks (e.g., bithiophene imide (BTI) 27, naphthalene diimide (NDI) 14,28, isoindigo (IID) 29, dithienyl diketopyrrolopyrrole (TDPP) 4, benzodifurandione-based oligo(p-phenylene
vinylene) (BDOPV) 30, and thienoisoindigo (TII) 31 ), primarily due to their
good backbone planarity and strong interchain interactions. (II) The
singlet-triplet energy gap (ΔEST = ES − ET) represents the energy difference between the singlet and triplet states 32 . As the energy level of
the singlet state approaches that of the triplet state, the organic

## d

P(TII-T)

P(TII-2FT)

_V_ DD

OECT1 OECT2

## a b

GND

_V_ in

_V_ out

## c

Au Layer

P(TII-2FT)

Vias

Parylene C

Au Layer

Parylene C

P(TII-2ClT)

Fig. 1 | Schematic illustration of using high-spin polymers for on-site biosignal
amplification. a Schematic illustration of a flexible OECT sensor matrix for capturing and amplifying mouse electrocorticogram (ECoG). b Diagram of the compact signal amplifier based on a cofacial vertical OECT pair and the corresponding

circuit diagram. c The layered device configuration of our device. d Chemical
structures of the three high-spin polymers, P(TII-T), P(TII-2FT), and P(TII-2ClT) used
for this study. Panel a was partly generated using Servier Medical Art under a
Creative Commons Attribution 3.0 unported license.

Fig. 2 | Polymer design and characterization. a Schematic illustration of the
transition from a closed-shell state to an open-shell state as the energy gap between
the singlet state and the triplet state decreases. b Resonance structures and the
amphoteric redox behaviors of P(TII-Ar), which could encompass both aromatic
type (closed-shell) and quinoid type (open-shell) structures. The “Ar” represents

semiconductor gradually transitions from a closed-shell to an openshell character (Fig. 2a) 33 . Simultaneously, the degree of overlap
between the highest occupied molecular orbital (HOMO) and the
lowest unoccupied molecular orbital (LUMO) of the material increases,
implying enhanced charge delocalization along the polymer backbone
and further stabilizing the electronic structure in a high-spin state 34,35 .
High-spin electronic structures usually exhibit rich redox
behaviors 36,37, with two electrons occupying two nearly degenerate
frontier orbitals, each capable of gaining or losing electrons. We propose that this characteristic could enable stable ambipolar charge
transport after doping (Fig. 2b). (III) The polymers must also have a
planar backbone for better intrachain/interchain charge transport.

Based on these assumptions, we screened available high-mobility
building blocks by calculating their ΔEST values (Fig. 2c). Among them,
TII exhibits the largest ΔEST value, suggesting that TII could possess the
most significant open-shell character. Thiophene (T), bithiophene
(2T), and thieno[3,2-b]thiophene (TT) are commonly used comonomers and were also employed for calculations. Compared to P(TII-2T)
and P(TII-TT), P(TII-T) demonstrates the largest ΔEST value (Supplementary Table 1, Fig. 2d, and Supplementary Fig. 3). Thus, TII and T
were selected for constructing the polymers. Based on P(TII-T), P(TII2FT) and P(TII-2ClT) were also designed (Fig. 1d), with two fluorine or
chlorine atoms introduced to tune the frontier orbital energy levels for
balanced hole/electron injection. Ethylene glycol (EG) side chains were
used to enhance the polymers’ hydrophilicity. Detailed synthesis and
characterization of the polymers can be found in Supplementary Fig. 4–7.

All the polymers display similar absorption features with optical
bandgaps below 1 eV (Fig. 3a and Supplementary Table 2). Notably, the
absorption spectrum of P(TII-T) shows a slight redshift compared to

the comonomers. c Calculated ΔEST values of the six commonly used high-mobility
building blocks. d Calculated ΔEST values of the three polymers: P(TII-T), P(TII-2T),
and P(TII-TT). 1, 2, 3, and 4 represent the number of repeating units used for
calculation.

P(TII-2FT) and P(TII-2ClT) (Fig. 3a and Supplementary Fig. 8), largely
due to its strong intramolecular charge transfer effects and strong
interchain aggregation (Supplementary Figs. 9–11). The absorption
spectrum of P(TII-2FT) reveals a pronounced vibronic absorption
shoulder at ~1067 nm, suggesting that P(TII-2FT) has a more planar
backbone in thin film, consistent with the relaxed potential energy
surface calculations (Supplementary Fig. 12). To further quantify the
backbone planarity, we used a planarization index 〈cos 2 φ〉 38, which
ranges between 0 (perpendicular) and 1 (coplanar) (see Supplementary Information for more details). The calculated results show that
〈cos 2 φ〉 values for P(TII-T), P(TII-2FT), and P(TII-2ClT) are 0.69, 0.72,
and 0.48, respectively. The higher 〈cos 2 φ〉 values indicate better
backbone planarity for P(TII-T) and P(TII-2FT) relative to P(TII-2ClT).
All the polymers display distinct reduction and oxidation peaks during
electrochemical operation (Supplementary Fig. 13). The HOMO/LUMO
energy levels were determined to be −4.59/−3.99 eV for P(TII-T), −4.76/
−4.05 eV for P(TII-2FT), and −4.89/−4.03 eV for P(TII-2ClT), respectively, consistent with the density functional theory (DFT) calculations
(Supplementary Table 2 and Supplementary Fig. 14). Spectroelectrochemistry was also performed. All the polymers showed new
absorption peaks (>1250 nm) in the long-wavelength region with
decreased neutral polymer absorption (800–1200 nm), irrespective of
reduction or oxidation, which can be attributed to the formation of
polarons/bipolarons after doping (Fig. 3b, c, Supplementary
Fig. 15–17).These results suggest thatthe three polymerscan bereadily
p-doped or n-doped, promising for ambipolar charge transport.

Electron paramagnetic resonance (EPR) spectroscopy is
employed to assess the open-shell characteristics of the polymers. At
room temperature, P(TII-2ClT), P(TII-2FT), and P(TII-T) all exhibited
strong EPR signals (Fig. 3e). We also synthesized other polymers with

Fig. 3 | Optoelectronic and electrochemical properties of the polymers.
a Normalized UV-vis-NIR absorption spectra of P(TII-T), P(TII-2FT), and P(TII-2ClT)
in thin film. Electrochemical absorption spectra of P(TII-2FT) with b positive voltages (0 to +0.8 V) and c negative voltages (0 to −0.8 V) on ITO glass in 0.1 M NaCl
aqueous solution. The ΔAbs. represents the difference in absorption intensity at

different building blocks (e.g., P(gTDPP2FT))and side chains (e.g., alkyl
chains) for comparison (Supplementary Figs. 12 and 18). All the results
indicate the presence of unpaired electrons in their backbone and the
polymers adopt an open-shell electronic structure. DFT-calculated
ΔEST and y0 values indicate that the order of the open-shell characteristics is as follows: P(TII-T) > P(TII-2FT) > P(TII-2ClT) (Fig. 3d and
Supplementary Fig. 19). Compared to the closed-shell polymer
P(gTDPP2FT) with a TDPP moiety, we can conclude that the open-shell
characteristics of these polymers originate from the TII moiety.
Variable-temperature EPR spectroscopy showed that both P(TII-T) and
P(TII-2FT) exhibited a decreasing trend in EPR signals as the temperature increased (Fig. 3f and Supplementary Fig. 20), suggesting the
presence of a triplet high-spin ground state in both materials 39,40 .

OECT device fabrication and characterization
The OECT devices based on the polymers were prepared using a photolithography and parylene patterning method 13 . The OECT performance of the polymers was characterized in an aqueous environment
(0.1 M NaCl). All three polymers showed satisfactory ambipolar behaviors (Fig. 4a, b, and Supplementary Fig. 21–27). To evaluate the OECT
performance of the polymers, the Bernards’ model was used (Eq. 1) 41 .

gm = ðW =LÞ � d � μ � C * �jðV Th � V GSÞj ð1Þ

where gm, µ, and C* are the transconductance, charge carrier mobility,
and volumetric capacitance; W, L, and d are the channel width, length,
and film thickness; VTh and VGS are the threshold voltage and the voltage between the gate and source electrodes. In the model, a figure-ofmerit, μC*, can be extracted to evaluate the performance of an OECT
material 42 . The p-type/n-type μC* values are 122.2/16.4 F cm −1 V −1 for
P(TII-T), 83.2/71.5 F cm −1 V −1 for P(TII-2FT), and 96.4/63.0 F cm −1 V −1 for
P(TII-2ClT), respectively (Supplementary Table 3). It can be seen that
the overall ambipolar steady-state performance of P(TII-2FT) is higher

various bias voltages. d Calculated ΔEST and y0 values of the polymers. The y0 value,
ranging from 0 (closed-shell) to 1 (pure diradical), can be used to evaluate the
diradical characteristic. e Comparison of the room-temperature EPR signals of the
three polymers with P(gTDPP2FT) in the solid state. f Variable-temperature EPR
signals of P(TII-T) in the solid state from 5 K to 70 K.

and more balanced. To achieve optimal OECT performance, the three
polymers were further fractionated using preparative GPC to narrow
the molecular weight distribution (Supplementary Fig. 28–35, and
Supplementary Table 4). The purified P(TII-2FT) exhibited a remarkable p-type μC* of 158.6 F cm −1 V −1 and an n-type μC* of 147.4 F cm −1 V −1,
setting a high standard for ambipolar OECT materials (Fig. 4f and
Supplementary Table 5). Compared with P(TII-T) with a large n-type
and small p-type VTh (0.76 V and −0.10 V), P(TII-2FT) and P(TII-2ClT)
exhibited more balanced VTh values.

The C* values for OECTs operating in the p-regime/n-regime were
measured to be 157/203 F cm −3 for P(TII-T), 88/138 F cm −3 for P(TII2FT), and 180/214 F cm −3 for P(TII-2ClT), respectively (Supplementary
Fig. 36). These values are comparable to those of other highperformance OECT polymers 43,44 . Using μC* and C*, the evaluated
hole (μh) and electron mobilities (μe) of the polymers are 0.78/
0.08 cm 2 V −1 s −1 for P(TII-T), 1.80/1.07 cm 2 V −1 s −1 for P(TII-2FT), and 0.54/
0.30 cm 2 V −1 s −1 for P(TII-2ClT), respectively. These results indicate that
P(TII-T) exhibits hole-dominant transport, whereas P(TII-2FT) and
P(TII-2ClT) exhibit relatively balanced hole and electron transport.
Compared with the pure n-type material P(gTDPP2FT) 18, P(TII-2FT)
exhibits ideal ambipolar OECT characteristics by replacing the TDPP
with TII. This highlights the efficacy of utilizing ΔEST to select the
comonomer for ambipolar OECT materials. Furthermore, we evaluated
the response speed of their OECT devices (Fig. 4c, d, Supplementary
Figs. 37, and 38). All the polymers exhibited fast responses with τon/τoff
on the scale of several milliseconds, comparable to the state-of-the-art
p-type and n-type materials 44 . Under long-term cycling and continuous
charging conditions, the stability of all three polymers significantly
outperforms previously reported ambipolar polymers (Fig. 4g and
Supplementary Figs. 39–41). For P(TII-2FT), it maintains 94% of the
original current after 1000 cycles of cycling measurements in the air
(Fig. 4e), and exhibits higher current retention under p-doped/ndoped operation (Supplementary Fig. 40). Furthermore, its OECT

Fig. 4 | OECT device and logic circuits fabrication and characterization.
a Transfer and b output characteristics based on P(TII-2FT) (W/L = 100/10 µm).
Transient response behavior of the c p-type and d n-type working regime of P(TII2FT). e Operational stability over 1000 on-off cycling and alternating polarities of
the OECT device. f Performance and g device stability comparison of our polymers
with some state-of-the-art p-type, n-type, and ambipolar OECT materials (Supplementary Tables 5 and 6). h Comparison of the gain and supply voltage of the

performance shows negligible changes after being stored in the air for
2 months (Supplementary Fig. 42), suggesting tremendous potential
for large-scale integration in logic circuits and amplifiers. We also
analyzed their polymer film microstructures and found that the higher
crystallinity and minimal morphology change of P(TII-2FT) after doping might explain its excellent performance and satisfactory stability
(Supplementary Figs. 43–46).

Logic circuits fabrication and characterization
Recently, a new OECT device configuration, namely the cofacial vertical OECT (vOECT) 14, was proposed to increase the integration level
and reduce the overall device size. However, this work only demonstrated moderate device performance due to poor OECT performance
and stability. To fabricate high-performance single-component vOECT
circuits, P(TII-2FT) has been employed to create vOECTs (Fig. 1b), in
which two metal layers are separated by a parylene insulating layer
serving as the source/drain contacts and interconnects. The thickness

different types of inverters (Supplementary Table 7). i Circuit diagram and j voltage
input and output behavior given by the NOR gate based on P(TII-2FT). k A flexible
transistor array with 300 × 300 inverters attached to the back of a hand (scale bar:
1 cm). l Microscope image of the inverter array. Inset: enlarged microscope image
of the inverter array (blue dashed line: VDD electrode contour; purple dashed line:
VSS or VGND electrode contour; green dashed line: VOUT electrode contour; red
dashed line: ambipolar OECT material channel contour; scale bar: 100 μm).

of the parylene layer roughly determines the vOECT channel length
(0.5 μm), and the width of the OECT is defined by the etched area
(100 μm) in photolithography (see Supplementary Information for
more details). The vOECT inverters based on P(TII-2FT) demonstrated
an ultra-high gain (∂Vout/∂Vin) of 809 V/V at a voltage step size of
0.1 mV with a simple device fabrication process (Supplementary
Figs. 47 and 48). This gain, obtained under a low supply voltage (VDD)
of 0.8 V, is significantly higher than that of previously reported inverters based on OECTs and OFETs (Fig. 4h). Interestingly, we observed
reduced inverter gains with larger voltage step sizes (Supplementary
Fig. 49), showing a gain of 272 V/V at a 1 mV step and 30.1 V/V at a
10 mV step. NAND and NOR gates were also fabricated based on P(TII2FT) (Fig. 4i, j, and Supplementary Fig. 50). We defined the output
voltage below 0.05 V as ‘0’ and the voltage above 0.55 V as ‘1’. All the
devices showed correct logic operations, demonstrating the possible
creation of complex logic circuits using a single material. Additionally,
we successfully fabricated a flexible array consisting of 300 × 300

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

1 Hz
2 Hz 5 Hz
10 Hz

L-929

P(TII-2FT)

Petri Dish

41.1 V/V
119 V/V
273 V/V _V_ in

413 V/V 340 V/V _V_ out

50 Hz
100 Hz

27.5 V/V

d _V_ DD e

_V_ in

0 2 4 6 8 10 12

Time (s)

Original EEG signal Amplified EEG signal

_V_ in

_V_ DD

1 s

Original ECG signal Q S Amplified ECG signal

_V_ in

GND
_V_ out

GND

_V_ DD

1 s

Original ECoG signal

2 s

Amplified ECoG signal

2 s

g h

AgCl/Ag ( _V_ in)

_V_ DD

_V_ SS

_V_ out

Fig. 5 | Biosignal amplification using P(TII-2FT)-based amplifiers. a Schematic
illustration of cell viability tests on P(TII-2FT) film. b Live (green fluorescence)/dead
(red fluorescence) staining of mouse fibroblasts (L929) on P(TII-2FT) film (scale bar:
100 μm). c Dynamic response of the amplifier using small sinusoidal signals at
different frequencies. The corresponding gains at different frequencies are also
displayed. d Schematic illustration of the vOECT amplifier for recording (e) EEG and
f ECG signals. g Photograph of in vivo ECoG recording and schematic of the electrical wiring (scale bar: 2 mm, inset: 100 μm). h Microscopic image of the amplifier

vOECT inverters, equivalent to an inverter density of 78,125 cm –2

(Fig. 4k, l, and Supplementary Fig. 51), highlighting the significant
advantage of the ambipolar vOECT device structure in enhancing
device integration and reducing space occupation.

On-site biological amplification
The biocompatibility of P(TII-2FT) was evaluated by cell viability tests.
Live/dead staining results showed that all mouse fibroblasts (L929)
cultured on the P(TII-2FT) film were alive (green fluorescence) with no
significant difference compared to the control group, revealing low
cytotoxicity and good biocompatibility of our polymers (Fig. 5a, b).
The high gain of P(TII-2FT)-based inverters decreases significantly as
the frequency increases (Fig. 5c), similar to other CMOS-like inverters
(see below Supplementary Fig. 54 for more details). At a high frequency of 100 Hz, the gain still maintains a value of 27.5 V/V, demonstrating excellent voltage amplification capabilities and suitability for
on-site sensing and amplification of electrophysiological signals. Subsequently, flexible amplifiers based on P(TII-2FT) were fabricated (see
Supplementary Figs. 52 and 53 for more details) to capture and amplify

array (scale bar: 200 μm). i Photograph of an ultrathin (10 μm) and flexible amplifier
array attached to a finger joint (scale bar: 1 cm). j The ECoG signals of the cortex
in vivo recorded by a metal electrode or a P(TII-2FT) amplifier. The time-frequency
analysis diagram of the signal from the amplifier. In the ECG, EEG, and ECoG signals,
the black lines represent the electrode-collected signals, and the orange lines
represent the signals from our amplifier. Panel a was partly generated using Servier
Medical Art under a Creative Commons Attribution 3.0 unported license.

human EEG (electroencephalogram), ECG (electrocardiogram), and
mouse ECoG (electrocorticography) signals (Fig. 5). The EEG of participants before and during mental arithmetic tasks was utilized for
testing 45 . We collected EEG signals synchronously using a conventional
metal electrode and the amplifier. To eliminate power line interference, we applied a high-pass filter with a cutoff frequency of 3 Hz
and a notch filter at 50 Hz (Fig. 5e). The amplifier exhibited an SNR of
21.5 dB, while the metal electrode only showed an SNR of 9.2 dB.
Similarly, ECG signals can also be recorded by attaching an electrode
to the subject’s skin near the heart, enabling the capture of cardiac
signals. The amplifier can amplify these signals with a high SNR of
31.9 dB, and the QRS complex peaks, P wave, and T wave are well
duplicated (Fig. 5f), meeting the requirements of functional ECG
recording. Remarkably, the output ECG signal achieved a magnitude of
46.3 mV, 73 times higher than the initial voltage collected by the
conventional electrode (Fig. 5f). Such on-site amplifiers possess several
advantages over conventional ECG detectors, including high gain,
considerable SNR, compact size, and portability, which could facilitate
remote ECG monitoring and cardiac disease diagnosis.

Fig. 6 | Computational study and comparison of high-spin polymers and other
OECT polymers. a Chemical structures and μC* values of four polymers: P(bgDPPMeOT2) (p-type); P(gTDPP2FT) (n-type); P(gNDI-gT2) (ambipolar), and P(TII-2FT)
(ambipolar). The side chains of each polymer are omitted for clarity. b LUMO energy
levels and n-doped backbone planarity. 〈cos 2 φ〉 − is the 〈cos 2 φ〉 value of the polymer

The voltage amplifiers were then used to record the electrocorticogram (ECoG) signals of the cortex in vivo. The voltage amplifiers were placed on the dura mater of a mouse after craniectomy.
During the test, ECoG signals were collected using an AgCl/Ag electrode as the ground electrode and brain tissue fluid as the electrolyte
(Fig. 5g). The devices successfully achieved on-site amplification
(Fig. 5j), but compared to static tests and external electrode measurements, the amplification factor is only 5 to 10 times that of conventional electrodes. This unexpectedly low amplification factor might
be due to the high signal frequency and complex solution environment
within the brain tissue fluid (Supplementary Fig. 54). However, this
does not mean that the quasi-static gain is insignificant for practical
application. First, the quasi-static gain can be used to determine the
suitable operating scenarios for an inverter. Smaller quasi-static measurement step aligns with smaller input signals, which could show
larger gains. Quasi-static gain can also serve as an upper limit for actual
amplification performance. Second, the gain may decrease at higher
signal frequencies and is largely influenced by various environmental
factors. Third, quasi-static gain also reflects the overall operational
stability of an inverter (see Supplementary Fig. 54 for more details).
Overall, we successfully realized on-site and in vivo biosignal capture
and amplification using a single high-spin conjugated polymer, which
provides a soft interface with tissues and could be further chemically
modified for additional biofunctions, such as bioadhesion 11 .

in an negatively charged state. c N-doped stability (ΔE − ). d HOMO energy levels and
p-doped backbone planarity. 〈cos 2 φ〉 + is the 〈cos 2 φ〉 value of the polymer in a positively charged state. e P-doped stability (ΔE + ). f Comparison of the six parameters
affecting the device performance of the four polymers. Spin density distribution of
the positively or negatively charged (g) P(gNDI-gT2) and h P(TII-2FT).

Understanding of the high-spin conjugated polymer design
We propose six parameters (HOMO and LUMO energy levels, polaron
stability, and backbone planarity after doping) to correlate our highspin polymer design with ambipolar OECT performance (Fig. 6f). Highlying HOMO/low-lying LUMO energy levels can facilitate hole/electron
injection from the source and drain electrodes 46 . ΔE + and ΔE − were
proposed to evaluate polaron stability (or doped stability). ΔE + represents the energy difference between the neutral and positively charged
states (ΔE + = Epositive − Eneutral), and a smaller ΔE + value indicates better
stability after p-doping, and vice versa. After doping, the backbone
planarity may change 47, and a planar backbone can benefit charge
transport. The 〈cos 2 φ〉 +/− values were employed to evaluate polymer
backbone planarity after p-doping/n-doping. All these parameters can
be obtained using DFT calculations (see Supplementary Fig. 55 for
more details).

Four representative polymers are used for comparisons
(Fig. 6a–e) 18,48,49 . P(bgDPP-MeOT2) has a high-lying HOMO energy level
and the highest stability and backbone planarity after p-doping, making it undoubtedly a p-type polymer. P(gTDPP2FT), featuring a lowlying LUMO energy level and better stability and backbone planarity
after n-doping, is an n-type polymer. Both P(TII-2FT) and P(gNDI-gT2)
span both p-type and n-type zones, exhibiting ambipolar behaviors.
However, despite P(gNDI-gT2) having the lowest LUMO energy level
and good stability in both p-doped and n-doped states, its ambipolar

OECT performance is much lower than that of P(TII-2FT). This is largely
due to its twisted backbone after doping, leading to substantially lower
charge carrier mobility (Fig. 6f). The spin density distribution of the
charged P(gNDI-gT2) and P(TII-2FT) supports this observation (Supplementary Figs. 56–58). In the case of P(TII-2FT), the charges are
uniformly distributed throughout the trimers, irrespective of being
positively or negatively charged (Fig. 6h). For P(gNDI-gT2), the positive
or negative charge is strongly localized (Fig. 6g), further impeding
charge transport along the polymer backbone 50 .

P(TII-2FT) shows balanced ambipolar behavior, while P(TII-T) is
hole-dominated. This experimental result coincides with the sixparameter radar chart (Supplementary Fig. 61). P(TII-T) only satisfies
the three parameters for the p-type regime, hence exhibiting high
p-type and weak n-type OECT performance. In contrast, P(TII-2FT)
matches the six parameters in both p-type and n-type regimes, displaying balanced p-type and n-type OECT performance. We further
experimentally demonstrate that the unmatched LUMO energy level of
P(TII-T) is the origin of its weak n-type performance (Supplementary
Fig. 62). The obvious difference between the two high-spin polymers
evidences that the high-spin electronic structure only endows the
material with more stable polarons and good backbone planarity than
traditional closed-shell polymers. However, the high-spin nature does
not provide suitable HOMO/LUMO energy levels for efficient charge
injection and balanced charge transport. Therefore, functional groups,
such as fluorine or chlorine atoms, were introduced to tune the hole/
electron injection. Both P(TII-2FT) and P(TII-2ClT) show more efficient
electron injection than P(TII-T), indicating that suitable HOMO/LUMO
energy level engineering is necessaryfor our high-spin polymer design.
Supplementary Fig. 63 shows the relationships among our high-spin
design, the six parameters, and ambipolar OECT performance. In
addition to the TII polymer system, a widely used building block, TDPP,
was employed to construct unique high-spin conjugated polymers. In
this system, we employed high-spin monomers BT and TQ for design,
and all the new polymers also show satisfactory ambipolar OECT
performance (Supplementary Fig. 64–66), further demonstrating the
generality and effectiveness of our high-spin polymer design strategy.

Discussion
In summary, we have proposed a general and effective strategy to
screen potential building blocks for designing high-performance,
stable, and balanced ambipolar OECT polymers. The high-spin polymer, P(TII-2FT), demonstrates balanced and remarkable ambipolar
properties, 5 to 20 times higher than current state-of-the-art materials,
with satisfactory operational stability in aqueous media. Based on
P(TII-2FT), we realized single-component flexible logic circuits and
amplifiers with ultrahigh gains of over 800 V/V at a voltage step size of
0.1 mV. P(TII-2FT) also shows good biocompatibility, suitable for onsite biosignal amplification. Several biosignals, such as human ECG,
EEG, and mouse ECoG, can be amplified using a single-component
amplifier with a higher SNR than conventional electrodes. We believe
this exceptional demonstration of single-component polymer in vivo
amplifiers could enable more polymer-based bioelectronics with soft
and multifunctional biointerfaces.

Methods
The EEG and ECG measurements were approved by the Institutional
Review Board (Approval number: PUIRB-2023139). These data were
recorded from a male volunteer who is 24 years old at the time of the
study (2024). And informed written consent was obtained prior to
subiect participation. The animal experiments were supervised and
approved by the Animal Care & Use Committees at Tsinghua University
(THU-LARC-2023-008). Our study is not related to the differences
between individuals (e.g., age, gender, race, ethnicity, and racism). We
only needed to ensure that the samples could provide valid biological
signals.

Materials
All the chemical reagents were purchased and used as received
unless otherwise indicated. All air and water-sensitive reactions
were performed under a nitrogen atmosphere. Dichloromethane
(DCM), tetrahydrofuran (THF), toluene, and N, N-dimethylformamide
(DMF) were dried using a JC Meyer solvent drying system
before use. Ultradry solvents were obtained from J&K reagent
company.

Cytotoxicity
The sample substrate was preloaded into a 6-well plate. 5 × 10 5

mouse fibroblasts (L929) were seeded into each well and cultured in
high glucose DMEM with 10% fetal bovine serum (FBS, 6021031,
DAKEWE), 100 U/mL penicillin (Invitrogen), and 100 μ/mL streptomycin (Invitrogen) at 37 °C with 5% CO2 and 95% humidity. After 24 h, a
live/dead staining assay (cat# 40747ES76, Yeasen) was performed to
evaluate the biocompatibility of the substrates. Briefly, cells
were washed with 1×Assay Buffer. A working solution was prepared by
adding 2 mM Calcein-AM solution and 1.5 mM PI solution to 5 mL of
1×Assay buffer. The working solution and assay buffer were added to
the cell culture plates at a ratio of 1:2 and incubated at 37 °C for 15 min.
Live cells (green fluorescence) and dead cells (red fluorescence) were
excited with a 490 ± 10 nm laser (Nikon DS-F).

Simulated EEG monitoring
The amplifier and the Au electrode, both with the same effective area
on the same flexible device, were positioned on an agar model (2 wt%).
An AgCl/Ag electrode was inserted into the model to simulate the EEG
signal source. The signals from the Au electrode and amplifier were
recorded using the Fs-Pro semiconductor parameter analyzer, PDA.
MATLAB was used for software filtering. The signals were digitally
filtered using a 50 Hz notch filter.

Preparation for in vivo ECoG recording
For the in vivo experiments, mature female C57BL/6 mice, 8 weeks of
age (Charles River Laboratories), were used throughout this study.
The mice were maintained at 22 ± 1 °C with humidity ranging from
30% to 70% and were kept on a 12-h light/dark cycle, with ad libitum
access to food. All 910 experiments were supervised and approved
by the Animal Care & Use Committees at Tsinghua University (THULARC-2023-008). During the surgery, the mice were anesthetized
with oxygen-vaporized isoflurane (3% for induction, 1.5–2% for
maintenance, 0.5 L/min). Body temperature was maintained at 37 °C.
Craniotomies (three craniotomies of 1 mm 2 for testing and larger
craniotomy over 20 mm 2 for visualization) were performed on the
skull to expose the cortical surface without removing the dura mater.
One silver wire coated with silver chloride was inserted into the
cortex to a depth of about 0.5 mm through the craniotomies, serving
as the ground electrode. The flexible amplifier was placed in
another opening. The craniotomy where the flexible amplifier was
positioned was done in different locations revealing various cortical
areas such as the motor (M1), somatosensory (S1), and primary visual
(V1) cortices. During subsequent tests, a metal bar was affixed to the
mouse’s skull using dental methacrylate to stabilize the mouse’s
brain. The FPC connected to the flexible amplifier was secured to the
metal fixed bar to prevent the device from moving on the
mouse’s brain.

Reporting summary
Further information on research design is available in the Nature
Portfolio Reporting Summary linked to this article.

Data availability
The data that support the findings of this study are available from the
corresponding authors upon request.

Code availability
The code that supports the findings of this study is available from the
corresponding authors upon request.

References
1. Lin, Q. et al. Wearable multiple modality bio-signal recording and
processing on chip: a review. IEEE Sens. J. 21, 1108–1123 (2021).
2. Zhou, F. & Chai, Y. Near-sensor and in-sensor computing. Nat.
Electron. 3, 664–671 (2020).
3. Cea, C. et al. Enhancement-mode ion-based transistor as a comprehensive interface and real-time processing unit for in vivo
electrophysiology. Nat. Mater. 19, 679–686 (2020).
4. Musk, E. An integrated brain-machine interface platform with
thousands of channels. J. Med. Internet Res. 21, e16194 (2019).
5. Khodagholy, D. et al. Neurogrid: Recording action potentials from
the surface of the brain. Nat. Neurosci. 18, 310–315 (2015).
6. Tang, X., Shen, H., Zhao, S., Li, N. & Liu, J. Flexible brain–computer
interfaces. Nat. Electron. 6, 109–118 (2023).
7. Shen, K., Chen, O., Edmunds, J. L., Piech, D. K. & Maharbiz, M. M.
Translational opportunities and challenges of invasive electrodes
for neural interfaces. Nat. Biomed. Eng. 7, 424–442 (2023).
8. Huang, W. et al. Vertical organic electrochemical transistors for
complementary circuits. Nature 613, 496–502 (2023).
9. Chen, J. et al. Highly stretchable organic electrochemical transistors
with strain-resistant performance. Nat. Mater. 21, 564–571 (2022).
10. Rivnay, J. et al. Organic electrochemical transistors. Nat. Rev. Mater.
3, 17086 (2018).
11. Li, N. et al. Bioadhesive polymer semiconductors and transistors for
intimate biointerfaces. Science 381, 686–693 (2023).
12. Ohayon, D. et al. Biofuel powered glucose detection in bodily fluids
with an n-type conjugated polymer. Nat. Mater. 19, 456–463 (2020).
13. Khodagholy, D. et al. High transconductance organic electrochemical transistors. Nat. Commun. 4, 2133 (2013).
14. Rashid, R. B. et al. Ambipolar inverters based on cofacial vertical
organic electrochemical transistor pairs for biosignal amplification.
Sci. Adv. 7, eabh1055 (2021).
15. Cea, C. et al. Integrated internal ion-gated organic electrochemical
transistors for stand-alone conformable bioelectronics. Nat. Mater.
22, 1227–1235 (2023).
16. Romele, P. et al. Multiscale real time and high sensitivity ion
detection with complementary organic electrochemical transistors
amplifier. Nat. Commun. 11, 3743 (2020).
17. Griggs, S. et al. The effect of residual palladium on the performance
of organic electrochemical transistors. Nat. Commun. 13,
7964 (2022).
18. Li, P., Shi, J., Lei, Y., Huang, Z. & Lei, T. Switching p-type to highperformance n-type organic electrochemical transistors via doped
state engineering. Nat. Commun. 13, 5970 (2022).
19. Wang, Y. et al. Acceptor functionalization via green chemistry
enables high-performance n-type organic electrochemical transistors for biosensing, memory applications. Adv. Funct. Mater.
[https://doi.org/10.1002/adfm.202304103 (2023).](https://doi.org/10.1002/adfm.202304103)
20. Yang, W. et al. High-performance n-type polymeric mixed ionicelectronic conductors: The impacts of halogen functionalization.
[Adv. Mater. https://doi.org/10.1002/adma.202305416 (2023).](https://doi.org/10.1002/adma.202305416)
21. Stein, E. et al. Ambipolar blend-based organic electrochemical
transistors and inverters. Nat. Commun. 13, 5548 (2022).
22. Samuel, J. J. et al. Single-component cmos-like logic using
diketopyrrolopyrrole-based ambipolar organic electrochemical
transistors. Adv. Funct. Mater. 31, 2102903 (2021).
23. Yang, J. et al. Isoindigo-based polymers with small effective masses
for high-mobility ambipolar field-effect transistors. Adv. Mater. 29,
1702115 (2017).

24. Ni, Z. et al. Mesopolymer synthesis by ligand-modulated direct
arylation polycondensation towards n-type and ambipolar conjugated systems. Nat. Chem. 11, 271–277 (2019).
25. Li, Y.-F., Guo, Y.-L. & Liu, Y.-Q. Recent progress in donor-acceptor
type conjugated polymers for organic field-effect transistors. Chin.
J. Polym. Sci. 41, 652–670 (2023).
26. Wang, S. et al. An organic electrochemical transistor for multimodal sensing, memory and processing. Nat. Electron. 6,
281–291 (2023).
27. Feng, K. et al. Cyano-functionalized fused bithiophene imide dimerbased n-type polymers for high-performance organic thermoelectrics. Adv. Mater. 35, 2210847 (2023).
28. He, T. et al. Site-specific chemical doping reveals electron atmospheres at the surfaces of organic semiconductor crystals. Nat.
Mater. 20, 1532–1538 (2021).
29. Zhou, Y.-Y. et al. Visualizing the multi-level assembly structures of
conjugated molecular systems with chain-length dependent
behavior. Nat. Commun. 14, 3340 (2023).
30. Wang, Y. et al. Green synthesis of lactone-based conjugated polymers for n-type organic electrochemical transistors. Adv. Funct.
Mater. 32, 2111439 (2022).
31. Parr, Z. S. et al. From p- to n-type mixed conduction in isoindigobased polymers through molecular design. Adv. Mater. 34,
2107829 (2022).
32. Sun, Z., Ye, Q., Chi, C. & Wu, J. Low band gap polycyclic hydrocarbons: From closed-shell near infrared dyes and semiconductors
to open-shell radicals. Chem. Soc. Rev. 41, 7857–7889 (2012).
33. Stuyver, T. et al. Do diradicals behave like radicals? Chem. Rev. 119,
11291–11351 (2019).
34. Hinz, A., Bresien, J., Breher, F. & Schulz, A. Heteroatom-based diradical(oid)s. Chem. Rev. 123, 10468–10526 (2023).
35. Yuan, D., Liu, W. & Zhu, X. Design and applications of singlecomponent radical conductors. Chem 7, 333–357 (2021).
36. Mori, S. et al. Medium diradical character, small hole and electron
reorganization energies and ambipolar transistors in difluorenoheteroles. Angew. Chem. Int. Ed. 61, e202206680 (2022).
37. Rudebusch, G. E. et al. A biradical balancing act: redox amphoterism in a diindenoanthracene derivative results from quinoidal
acceptor and aromatic donor motifs. J. Am. Chem. Soc. 138,
12648–12654 (2016).
38. Che, Y. & Perepichka, D. F. Quantifying planarity in the design of
organic electronic materials. Angew. Chem. Int. Ed. 60,
1364–1373 (2021).
39. Abe, M. Diradicals. Chem. Rev. 113, 7011–7088 (2013).
40. Chen, X.-X. et al. High-mobility semiconducting polymers with
different spin ground states. Nat. Commun. 13, 2258 (2022).
41. Bernards, D. A. & Malliaras, G. G. Steady-state and transient behavior of organic electrochemical transistors. Adv. Funct. Mater. 17,
3538–3544 (2007).
42. Inal, S., Malliaras, G. G. & Rivnay, J. Benchmarking organic mixed
conductors for transistors. Nat. Commun. 8, 1767 (2017).
43. Li, P. & Lei, T. Molecular design strategies for high-performance
organic electrochemical transistors. J. Polym. Sci. 60,
377–392 (2022).
44. Kukhta, N. A., Marks, A. & Luscombe, C. K. Molecular design strategies toward improvement of charge injection and ionic conduction in organic mixed ionic–electronic conductors for organic
electrochemical transistors. Chem. Rev. 122, 4325–4355 (2022).
45. Zyma, I. et al. Electroencephalograms during mental arithmetic task
performance. Data 4, 14 (2019).
46. Paterson, A. F. et al. On the role of contact resistance and electrode
modification in organic electrochemical transistors. Adv. Mater. 31,
1902291 (2019).

47. Xiao, M. et al. Charge transport physics of a unique class of rigid-rod
conjugated polymers with fused-ring conjugated units linked by
double carbon-carbon bonds. Sci. Adv. 7, eabe5280 (2021).
48. Giovannitti, A. et al. N-type organic electrochemical transistors with
stability in water. Nat. Commun. 7, 13066 (2016).
49. Jia, H. et al. Engineering donor–acceptor conjugated polymers for
high-performance and fast-response organic electrochemical
transistors. J. Mater. Chem. C 9, 4927–4934 (2021).
50. Fratini, S., Nikolka, M., Salleo, A., Schweicher, G. & Sirringhaus, H.
Charge transport in high-mobility conjugated polymers and molecular semiconductors. Nat. Mater. 19, 491–502 (2020).

Acknowledgements
This work is supported by National Natural Science Foundation of China
(T2425010 (Lei) and 22172085 (Dai)) and Beijing Natural Science Foundation (JQ22006 (Lei)). G.-Y. G. thanks the Boya Postdoctoral Fellowship
of Peking University. The authors thank Prof. Shenzhen Xu for his
insightful discussions on DFT calculations. We acknowledge Molecular
Materials and Nanofabrication Laboratory (MMNL) and Materials Processing and Analysis Center, Peking University, for the use of instruments.
The computational part is supported by the High-Performance Computing Platform of Peking University. The authors thank beamline BL14B1
(Shanghai Synchrotron Radiation Facility) for providing beam time.

Author contributions
G.-Y.G. and J.X. contributed equally to this work. G.-Y.G., X.P., and X.-Q.W.
synthesized the polymer and performed some characterization. J.X., P.L.,
and W.S. performed device fabrication and characterization. J.-T.L. performed AFM measurements. X.-Y.D. performed DFT calculations and EPR
measurements. Z.M. and S.L. performed cell viability tests. X.W., M.Y.,
and X.D. performed mouse ECoG tests. G.-Y.G., J.X., Z.Z., and T.L. wrote
the manuscript. All the authors revised and approved the manuscript.

Competing interests
The authors declare no competing interests.

Additional information
Supplementary information The online version contains
supplementary material available at
[https://doi.org/10.1038/s41467-024-55369-6.](https://doi.org/10.1038/s41467-024-55369-6)

Correspondence and requests for materials should be addressed to
Ting Lei.

Peer review information Nature Communications thanks the anonymous reviewers for their contribution to the peer review of this work. A
peer review file is available.

Reprints and permissions information is available at
[http://www.nature.com/reprints](http://www.nature.com/reprints)

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access This article is licensed under a Creative Commons
Attribution-NonCommercial-NoDerivatives 4.0 International License,
which permits any non-commercial use, sharing, distribution and
reproduction in any medium or format, as long as you give appropriate
credit to the original author(s) and the source, provide a link to the
Creative Commons licence, and indicate if you modified the licensed
material. You do not have permission under this licence toshare adapted
material derived from this article or parts of it. The images or other third
party material in this article are included in the article’s Creative
Commons licence, unless indicated otherwise in a credit line to the
material. If material is not included in the article’s Creative Commons
licence and your intended use is not permitted by statutory regulation or
exceeds the permitted use, you will need to obtain permission directly
[from the copyright holder. To view a copy of this licence, visit http://](http://creativecommons.org/licenses/by-nc-nd/4.0/)
[creativecommons.org/licenses/by-nc-nd/4.0/.](http://creativecommons.org/licenses/by-nc-nd/4.0/)

본문 출처 PDF: PDF 보기 · 다른 PDF는 위 [PDF 업로드]로 올릴 수 있습니다.

활용가능성

이력 0건

아직 편집 이력이 없습니다. 저장할 때마다 이전 내용이 여기에 백업됩니다.