用于即時檢驗的微流控紙基分析設(shè)備的研究進展

Abstract： Point-of-care testing （POCT） refers to a category of diagnostic tests that are performed at or near to the site of the patients （also called bedside testing） and is capable of obtaining accurate results in a short time by using portable diagnostic devices， avoiding sending samples to the medical laboratories. It has been extensively explored for diagnosing and monitoring patients’ diseases and health conditions with the assistance of development in biochemistry and microfluidics. Microfluidic paper-based analytical devices （μPADs） have gained dramatic popularity in POCT because of their simplicity， user-friendly， fast and accurate result reading and low cost. Several μPADs have been successfully commercialized and received excellent feedback during the past several decades. This review briefly discusses the main types of μPADs， preparation methods and their detection principles， followed by a few representative examples. The future perspectives of the development in μPADs are also provided.

Key words： point-of-care testing; microfluidic paper-based analytical devices; sensor; personalized medical treatment; portable diagnostic equipment

CLC number： TP212" " " " " " " " " " "Document code： A DOI： 10.3969/j.issn.1007-7146.2025.01.001

摘 要：即時檢驗（POCT）是指在患者現(xiàn)場或附近進行的一類診斷測試（也稱為床邊測試），能夠通過使用便攜式診斷設(shè)備在短時間內(nèi)獲得準確的結(jié)果，避免將樣本送往醫(yī)學實驗室。隨著生物化學分析和微流體檢測技術(shù)的發(fā)展，POCT已被廣泛用于診斷和監(jiān)測患者的疾病和健康狀況。微流控紙基分析設(shè)備（μPADs）因其簡單、用戶友好、快速準確的結(jié)果讀取和低成本而在POCT中廣受歡迎。在過去的幾十年里，一些μPADs已經(jīng)成功商業(yè)化應(yīng)用，顯示出很好的發(fā)展前景。本文簡要討論了μPADs的主要類型、制備方法及其檢測原理，并列舉了幾個具有代表性的例子，描繪了μPADs的未來發(fā)展前景。

關(guān)鍵詞：即時檢驗；微流控紙基分析設(shè)備；傳感器；個性化醫(yī)療；便攜式診斷設(shè)備

中圖分類號：TP212" " " " " " " " " " " " "文獻標志碼：A" " " " " " " DOI：10.3969/j.issn.1007-7146.2025.01.001

（Acta Laser Biology Sinica， 2025， 34（1）： 00-011）

With the growing human population and the aging demographic， healthcare faces significant challenges［1］. Every year， over 25 million people die from infectious diseases such as malaria， tuberculosis， and acquired immunodeficiency syndrome （AIDS）， representing one-quarter of all deaths［2］. Notably， more than 95% of these deaths occur in developing countries due to inadequate economic and medical support［3］. Most patients are unable to undergo regular medical tests in the early stage of the disease， leading to a deterioration in their health conditions. The failure to detect diseases early not only misses the optimal time for effective treatment， but also significantly increases the healthcare costs. Therefore， screening and early diagnosis of diseases are critical for efficient and effective healthcare.

Traditional clinical diagnosis requires skilled professionals to conduct tests using complex equipment， often involving the collection of blood samples or body fluids. This process is inefficient， encompassing a series of time-consuming and costly steps such as queueing， registration， and result waiting. In recent years， point-of-care testing （POCT） technology has rapidly developed， featuring miniaturization， low cost， and high sensitivity ［4］. It has increasingly been utilized in a various fields such as healthcare and environmental monitoring［5］， with some usage scenarios illustrated in Fig.1. Microfluidic paper-based analytical devices （μPADs） offer various advantages， including simplicity， user-friendliness， fast and accurate result reading， and low cost. They are" ideal techniques for POCT and meet the “ASSURED” criterial proposed by the World Health Organization （WHO）： affordable; sensitive （avoid 1-negative results）; specific （avoid 1-positive results）; user-friendly （simple to perform）; rapid and robust; equipment-free; delivered （accessible to end-users）［6］.

In recent years， the manufacturing techniques and test principles of paper-based sensors have significantly advanced， focusing on miniaturization， precision， multi-channel capabilities， multi-target detection， and user-friendliness. μPADs primarily comprise three components： 1） hydrophobic/hydrophilic channels， 2） the selection and application of sensor detection principle， and 3） the transmission and conversion of the detection signal. This review summarizes the current techniques for preparing μPADs and their detection principles over the past decade. Additionally， by examining commercialized μPADs products available on the market， it discusses existing challenges and future prospects.

1 Development of μPADs

1.1 From microfluidic to paper-based sensor

Microfluidic devices utilize microchips as the platform to precisely control the flow of micro-level fluids ［7］. They have been widely used in the field of analysis due to their rapid analysis speed， low reagent consumption， high resolution， and high sensitivity ［8］. However， with the increasing demand for POCT in recent years， traditional microfluidic devices fall short as they require external resources such as power， pumps， or syringes. Therefore， it is of great importance to develop miniaturized， high efficiency， low power consumption and low-cost sensors. The μPADs have drawn extensive attention as a promising candidate ever since it was introduced in 2007［9］. Paper-based sensor represent a novel detection technology that combines traditional detection methods with microfluidic control. They offer numerous advantages， including low-cost， minimal sample requirement， ease of use， portability， simple post-treatment， and flow pollution［10］. Various analytical methods are available for μPADs， including colorimetry， electrochemistry， chemiluminescence （CL）， electrochemiluminescence （ECL）， and fluorescence. Compared to enzyme-linked immunosorbent assays， these analytical approaches are more sensitive and simpler. Consequently， μPADs are increasing utilized in environmental monitoring， diseases diagnosis， cell culture analysis， and more ［11］.

1.2 Selection of paper-based substrates

Paper has been selected as the substrate for μPADs not only because of its abundance and extremely low cost， but also due to its fibrous and porous microstructure， which facilitates capillary action， absorbency， reagent storage air permeability， high surface-to-volume ratio， and efficient analysis process［12］. These advantages make paper an ideal substrate for POCT， providing a more convenient and versatile platform for various applications. Paper has been used as a detection substrate since the invention of litmus test paper by Müller and Clegg［13-14］. In 2010， Martinez et al.［10］ firstly proposed the use of paper as the base material for microfluidics， and successfully constructed the world’s first protein-glucose paper microfluidic sensor. It was an important milestone in the development of paper microfluidic sensors.

1.2.1 Traditional cellulose papers

Cellulose papers， such as filter papers and chromatographic papers， are widely used in μPADs. Given that μPADs are predominantly employed for medical applications， the substrate materials must meet safety and biocompatibility standards. Compared to other types of paper， cellulose papers do not contain structural enhancers or bleach， which can adversely affect fluid flow or reduce detection accuracy due to background discoloration［15］. Additionally， cellulose papers boast excellent toughness， thermal stability， and high adsorption capacity， making them the preferred substrate material for μPADs［16］. In 2005， Alila et al.［17］ discovered that increasing the negative charge density on the surface of cellulose enhances the electrostatic adsorption of positively charged compounds and has a weak electrostatic effect on macromolecules such as proteins.

1.2.2 Multi-functional “pseudo-paper”

In addition to traditional papers， flexible films with micro and nanostructures， referred to as “pseudo-paper”， have emerged as viable alternatives. Thanks to their excellent optical properties and structural advantages， “pseudo-paper” is increasingly being used to replace traditional cellulose papers as an ideal substrate. In 2019， Gao et al.［18］ designed and prepared μPADs using nitrocellulose multistructured pseudo-paper （NC-MSPs） and elastic copolymer multistructured pseudo-paper （EC-MSPS） as substrates. This microfluidics have three channels for simultaneous detection of cardio troponin （cTnI）， creatine kinase isoenzyme （CKMB） and myoglobin （Myo）， based on the capillary force characteristics of micron arrays.

1.3 Structure design of μPADs

1.3.1 Planar two-dimensional （2D） structure

So far， most of μPADs have 2D structure. In 2007， Martinez et al.［9］ invented a paper-based microfluidic which has a patterned hydrophobic channel on a hydrophilic paper. Since then， paper-based microfluidics with 2D planar structure have been extensively explored. Most of this paper-based microfluidics use hydrophobic agents to treat the paper through physical methods such as painting， dipping and printing， then channels are patterned using physicochemical methods such as batik and photolithography［19］. The final fluid flow is achieved by capillary action as mentioned above. In 2013， Li et al.［20］ designed a 2D magnetic timing valve， the authors claimed that the valve was managed to strictly control the testing process through the magnetic driven cantilever valve and accurately time the fluid flow in the channels through core suction， to achieve orderly multi-step detection.

1.3.2 Three-dimensional （3D） structure

Generally， most 3D paper-based microfluidics are prepared by stacking， folding or chemical bonding a pre-patterned 2D paper to form a multilayer microfluidic with connected hydrophobic/hydrophilic channels ［21］. The idea behind the 3D structural design of the paper-based microfluidics is to avoid the cross contamination between different processes such as biomolecular immobilization and electrode modification. Moreover， the detection channels in 3D microfluidics are more diverse than that of the 2D ones， therefore， 3D microfluidics can be used to detect more analytes in one test， thus saving test sample and are more efficient compared to 2D microfluidics.

Folding is the simplest and most commonly used method to prepare 3D μPADs. In 2012， Lu et al. ［22］ fabricated a μPADs using wax printing and origami （a Japanese paper folding skill）. Different types of analytes can be tested by replacing different substrates in the gripper as shown in Fig. 2a. In 2020， Cao et al. ［23］ and Jiao et al. ［24］ prepared a 3D electrochemical μPADs for glucose detection and a 3D vertical-flow μPADs for multiplexed detection of cancer biomarkers through origami respectively （Fig. 2b）. Both μPADs constructed by folding achieved high selectivity and sensitivity. However， although the origami scheme is easy to operate， the process is time-consuming and inconvenient. Moreover， the stability of the folded μPADs cannot be guaranteed. Li et al. ［25］ proposed a different construction method which was based on wax patterning for fabricating 3D μPADs. They successfully achieved 3D microfluidic channels in a single layer of cellulose paper by controlling the penetration depth of molten wax. Schilling et al. ［26］ significantly reduced the use of assembled materials by using carbon powder as a thermal adhesive between sheets to form hydrophobic channels between sheets of paper while enabling bonding.

3D μPADs are capable of tackling with complex fluid operation， parallel sample analysis and high-throughput multi-sample detection， which dramatically increases the efficiency of μPADs. However， the preparation processes of 3D μPADs are more complicated and tedious than that of 2D ones. Additionally， the channels are prone to leak once the blocking materials dissolve in the liquid media due to the multi-connection between different layers. Therefore， optimizing the design of 3D μPADs and simplifying their preparation processes are the current challenges to apply this microfluidics to wider applications.

2 Classification of paper microfluidic sensors

2.1 Lateral flow assay （LFA）

LFA， also known as lateral flow immunochromatographic analysis is a paper-based immunoassay which usually has four functional areas： 1） injection area （sample smear area）; 2） conjugate area; 3） reaction test area; 4） residual liquid absorption area. The flow of the test samples is enabled by capillary force between those four areas. So far， the most representative LFA device is pregnancy test strip which has accuracy higher than 99%. Therefore， it has been widely used to replace the traditional pregnancy test.

At present， nucleic acid detection （NAT） based on the LFA devices has been widely used in preclinical POCT. However， it is difficult to use LFA to detect micro-level dosed samples due to the structural limitations of the LFA devices. To solve this problem， Choi et al. ［27］ developed a LFA sensor based on handheld battery power， which integrated the paper-based nucleic acid amplification technology into colorimetric LFA. Taking the DNA of the dengue virus which is widely spread in developing countries as the model analyte， the naked eye can be judged according to the color change of the product by isothermal amplification （LAMP） technology combined with LFA for signal detection.

2.2 μPADs

Compared with LFA， μPADs are capable of detecting microliter dosed samples and achieving multi-index， multi-channel parallel analysis on account of their delicate designs ［28］. Therefore， μPADs significantly reduce the cost of test samples and consumables ［15］. μPADs have been used for various applications such as quantitative detection of bacteria， cells， viruses， nucleic acids and metabolites.

3 Fabrication of μPADs

Current fabrication techniques of μPADs can be categorized into three groups： 1） Physical modification： hydrophobic reagents are physically attached to the paper substrates and the hydrophobic effect is achieved by filling the gap between the fibers in the paper base， to complete the construction of pro/phobic channels. This technique mainly includes photolithography， wax printing， screen printing， inkjet solvent etching， drawing， laser treatment， inkjet printing ［9， 29］. 2） Chemical modification： hydrophobic reagents are chemically bonded to the paper substrates. The commonly used reagents are： alkyl ketene dimer （AKD）， fluoroalkyl silane， polystyrene， octadecyl trifluoro silane （OTS） and urethane acrylate （PUA）， etc［7］. 3） Reduction molding： directly cutting or carving paper to construct the fluid channels ［30］.

3.1 Physical modification

3.1.1 Photolithography

Photolithography is a microfabrication technique. Photoresist and ultraviolet irradiation （UV） have been widely used in the fabrication of paper-based microfluidics by patterning hydrophobic reagents on paper substrates to form hydrophilic zooms such as channels and reaction areas［31］. SU-8 is one of the most widely used photoresist because of its good mechanical properties， good thermal stability， and strong corrosion resistance to a variety of chemical reagents. Additionally， compared with other hydrophobic reagents （e.g. wax）， the SU-8 based channel has no resistance effect on hydrophobic fluids passing through it， thus resulting a smooth flow. Martinez et al.［9］ firstly fabricated a μPADs for detecting protein-glucose using photolithography in 2007. The paper substrate was hydrophobically treated with SU-8 adhesive， then covered with a mask and exposed under UV to form a hydrophobic channel. The unexposed adhesive was subsequently removed to form a specific hydrophobic zone and the hydrophobic passage was completed. The following year， Dungchai et al. ［32］ team built on earlier improvements， using double-sided adhesives to bond paper to create a paper microfluidic sensor with a 3D structure. But this approach is more complex. In 2011， Liu et al.［33］ combined origami and photolithography to produce a 3D sensor on a sheet of paper. Asano et al.［34］ used 3D printers to print photomask and fabricate hydrophobic channels on paper. There is also a method of making patterned channels with rubber seals， called soft lithography， which does not require masks. Xiang et al.［35］ used digital micro-mirror device （DMD） to modulate space light and project ultraviolet micrographs during exposure to photoresists film， also avoiding the use of physical masks.

3.1.2 Wax printing

Wax printing is one of the most commonly used methods for fabricating paper-based microfluidics because of its simplicity， fast process， environmental-friendly and low-cost［36］. Generally， wax is firstly printed on one or both sides of the paper surface in a desired configuration followed by a heating process， the printed wax melts and penetrates into paper to form hydrophobic channels. However， the lateral impregnation of wax in paper substrate is quicker than the penetration in the direction of paper thickness， thus resulting in rough edge and poor resolution of wax printed channels. To overcome this disadvantage， Songjaroen et al.［37］ proposed a wax dipping scheme instead of printing. Wax impregnation process needs to use melted wax， and the temperature of melted wax is generally required to be above 100 oC， which greatly reduces the scope of application of the wax impregnation process. Liu et al.［38］ reported a wax screen printing.

Although wax printing and wax screen printing have gained successes in fabricating paper-based microfluidics， they require extra heating step which reduces the resolution of patterned features. Li et al.［39］ developed a pen-on-paper （PoP） strategy which had two customized pens loading with wax and conductive inks respectively to directly write microfluidic channels and electrochemical sensing element as shown in Fig. 3. This PoP strategy did not need extra heating step to pattern wax， which not only simplified the pattering process， but also improved the resolution of patterned features. In recent years， with the remarkable development of 3D printing technology， the combination of 3D printing and wax-patterning provides a new approach for preparing paper-based microfluidics.

3.2 Chemical modification

Plasma contains many active particles such as electrons， ions， radical groups， and high energy molecules. Material surface can be modified by plasma by breaking or recombining the chemical bonds in the molecules. Paper plasma treatment is usually divided into two steps： 1） hydrophobic treatment on paper surface; 2） selectively regional plasma treatment to restore hydrophilicity. The plasma intensity and exposure time are two important parameters which determine the quality of the final patterns. High intensity and longtime of laser treatment negatively affect the final products. Li et al. ［25］ used the hydroxyl reaction of AKD with cellulose to hydrophobically modify paper， then applied plasma treatment to the hydrophobized paper， the AKD was degraded regionally and the local hydrophilicity was restored. Although the method is simple and feasible， the use of masks increases the cost of this method. Therefore， Li et al. ［25］ made improvements， combined with inkjet printing technology， directly print AKD on paper， after heating and curing， it can be an affinity and hydrophobic channels. This solution avoids the use of molds， can directly draw patterns through the computer， and the resolution of the prepared fluid channel is higher. Wang et al. ［40］used a modified fluoroalkyl silane （FAS） solution as the hydrophobic agent to form hydrophilic regions by oxygen plasma treatment with the aid of a metal mask. Additionally， plasma treatment can be also performed by utilizing UV irradiation. This method does not require large， professional instruments to prepare high-resolution hydrophilic channels.

3.3 Weight reduction method

The weight reduction method is to use cutting， engraving， embossing， folding and other physical treatments to treat the air around the channels as hydrophobic barriers to achieve the construction of the μPADs. Compared with other methods， the weight reduction molding method does not need any chemical reagent to treat the paper， thus minimizing the damage to the paper substrates. Besides， the fast molding and fabrication process make the weight reduction molding method a potential candidate for mass production of μPADs.

In 2009， Fenton et al.［30］ used the reduction molding method for the preparation of paper sensors for the first time and used a computer-controlled X-Y knife plotter to accurately cut paper. The accuracy can achieve the preparation of small radius right angles and holes. In 2010， Wang et al.［40］ were inspired by trees and cut the paper into a tree-shaped paper sensor with seven branches that can be used in combination with colorimetry. The cutting method greatly reduces the production cost of the paper sensor， but the channel resolution is not high， and it is difficult to form a smooth and neat cut during the cutting process， which will affect the fluid flow.

For this reason， Fang et al.［41］ replaced cellulose paper with brittle glass cellulose paper to achieve precise and smooth cutting. Therefore， in 2013， Nie et al.［42］ tried to replace the traditional cutting instrument with a CO2 laser cutting machine， which achieved a perfect one-step cutting and avoided the problems of sticking and assembly. Laser cutting not only takes a short time， but also can be combined with other paper cutting methods to prepare paper sensors through hot pressing， so laser technology is very popular in the preparation of paper sensors.

Compared with the wax printing method， the reduced forming method has higher resolution and easier operation， but whether by cutting instrument or laser cutting instrument， the reduced forming method is essentially an inheritance of the cutting method， that is， the preparation of the fluid channel is realized by changing the shape of the paper base. Therefore， the preparation principle has limited the expansiveness of its application function， such as the simultaneous detection of multiple detectors and the precise control of the fluid channel cannot be realized.

4 Detection strategies

There are several detection strategies have been used in μPADs， including colorimetry， fluorescence， CL， ECL， photoelectrochemical （PEC） and surface-enhanced Raman spectroscopy （SERS）. Among which， colorimetry is the most popular detection method whose results can be directly observed by the naked eye. CL and ECL are highly sensitive， selective， low-cost， and are not affected by the sample color. However， the electrodes are easy to be contaminated and the test samples must possess electrochemical properties. Although the SERS has high sensitivity and low detection limit， it is prone to be affected by the fluorescence dye and the fluorescein background of the paper. Additionally， relying on complex detection instruments is another drawback of using this detection strategy. Tab.1［22］ compares the different detection strategies in terms of test method and the concentration ranges of detectable analytes.

4.1 Electrochemistry

Electrochemistry-based μPADs produce digitized results rather than colour signals generated by colorimetry-based ones. The digital output can be recorded through simple electronic devices［43］. The principle of the electrochemistry is to combine the liquid analytes with the electro-analytical sensors to form a chemical battery， which analyses the content in the test samples according to the electrical parameters generated by the electronic signals. Glucose meter is the most commonly used μPADs based on electrochemistry， it has lower detection limit and is not affected by the ambient illumination conditions and impurities in the analytes. Manbohi et al.［21］ used an electrochemical μPADs to sensitively and selectively detect dopamine in urine and blood samples. The linear detection range and limit of detection of dopamine were 0.50～120.00 μmol/L and 0.01 μmol/L， respectively. Alrammouz et al.［44］ developed a capacitive humidity sensor for airflow monitoring by self-assembling graphene oxide onto paper fibres. In addition， paper-based chemical resistance sensors have recently been reported for the rapid detection of nitroaromatic explosives. The flower-shaped polyaniline coating with high permeability and stability was prepared by spraying method， which contacted with trinitrotoluene （TNT） and dinitrotoluene （DNT） steam at room temperature to form current fluctuation and generate response value.

4.2 CL

CL μPADs have been successfully used for biomedical detections［45］. The detection principle is based on the light intensity generated by the chemical reaction. The CL detection method is a sensitive， low-cost and easy-to-operate analytical method for μPADs as the chemiluminescent reagents are inexpensive and do not require excessive complex instruments for detection［46］. By combining CL and immunoassay techniques， carcinoembryonic antigens in serum can be detected. Additionally， simultaneously detection of multiple biomarkers can be achieved by using multi-channel μPADs. The major disadvantages of the CL detection method are： 1） limited available chemiluminescent reagents; 2） the existing chemiluminescent reagents have certain limitations; 3） the CL method needs to decompose the substrate through an enzyme reaction; thus， a higher concentration of enzyme is needed and may be blocked; 4） the porous structure has a certain influence on the detection efficiency; 5） an extra CL reader is needed which increases the cost of using this method.

4.3 ECL

ECL combines electrochemical and CL， producing luminescence through electrochemical reactions. Since Delaney et al.［47］" constructed the first paper-based ECL microfluidic sensor in 2011， this detection technique has been increasingly applied in μPADs due to its advantages of low background noise， good stability and selectivity， and excellent controllability［48］. ECL μPADs have been used to detect various biomolecules such as proteins， cancer cells， and tumour markers， showing great potential for POCT applications. However， despite its controllability and selectivity， the output signal of ECL is often weak due to low detectable contents in samples.

4.4 SERS

SERS is a highly sensitive， labeling-free technique that can be used as the microscopic scale， making it suitable for integration with μPADs for POCT recently. Hu et al.［49］ used AuNP paper as a SERS matrix for cancer cells screening through immunomagnetic binding and specific recognition between target cells. Xu et al.［50］ self-assembled 3D-AgNFs and AgNPs on paper to enhance SERS performance， allowing for the detection of crystal violet （CV）. Lin et al.［51］ assembled Au@AgS basement on paper as SERS sensor， which was then glued to a slide to construct a new label-free SERS sensor for soil pesticide fuming double detection.

4.5 Fluorescence

Fluorescence detection measures the fluorescence intensity emitted by a molecule after it absorbs energy， with a fluorescence analyzer is used to quantitative analysis. Wang et al.［52］ developed a bifunctional molecularly imprinted polymer-coated paper sensor （MIP-CP Sensor） for the fluorescence detection and visual analysis of norfloxacin in drugs and environmental water sources. Jiao et al. ［24］ developed a 3D vertical-flow paper-based device （3VPD） integrated with a sandwich-type fluorescent immunoassay for the simultaneous detection of multiple tumor biomarkers. However， fluorescence detection in μPADs has intrinsic drawbacks： 1） fluorescent dyes are prone to light scattering; 2） photobleaching can occur; 3） paper has self-fluorescence， causing significant background noise.

4.6 Absorbance

Absorbance is an analytical method based on the selective absorption of light from a non-fluorescent substance. Ellerbee et al.［53］ utilized μPADs and a tricolor hand-held transmissivity colorimeter to create a POCT system that determine protein content by measuring absorbance before and after light transmission. Due to its simplicity and high sensitivity， the detection sensitivity is directly proportional to the absorption optical path. However， the channel structure of the microfluidic sensor for paper chips often affects the absorption optical path， reducing sensitivity and limiting its application.

5 Conclusions and future perspectives

Since the first μPAD was invented in 1941， it has become a crucial technique in the field of POCT （Fig. 4）. Due to their simplicity， affordability， disposability， and user-friendliness， μPADs have been well received by clinical patients， particularly in resource-limited countries. With the remarkable development of internet and smartphones， researchers are actively developing telemedicine services that connect μPADs to the internet or smartphones， enabling quicker and more convenient diagnosis. In the future， the direction of medical development is expected to lean more towards personalized medicine and telemedicine. Patients will be able to use the corresponding μPADs at home and send the results directly to relevant medical services and professionals. Personalized medical treatment plans and medications can then be provided based on immediate detection results. Consequently， the current hospital-centered diagnosis model will shift towards a patient-centered approach， allowing for pre-medical diagnosis without leaving home.

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收稿日期：2024-05-26；修回日期：2024-07-18。

基金項目：國家自然科學基金面上項目（22274075）。

作者簡介：張玉基，博士研究生。

*通信作者：單丹，教授，主要從事電化學，光、電生物傳感、功能性納米材料以及生物燃料電池的研究。E-mail： danshan@njust.edu.cn。

Received date：2024-05-26; Revised date： 2024-07-18.

Foundation items：National Natural Science Foundation of China （22274075）.

Biography：ZHANG Yuji， doctoral candidate.

*Communication author：SHAN Dan， professor， primarily engaged in the research of electrochemistry， light and electric biosensing， functional nanomaterials and biofuel cells. E-mail： danshan@njust.edu.cn.