Fluorescence method is one of the common optical techniques, which is often used in the field of aptamer-based biochemical detection. Some analytes can not emit fluorescence by themselves, so fluorescent probes are usually constructed by modifying fluorescent agents at the end of aptamers or nucleic acid chains to provide fluorescent signals^[23⇓~25]. One of the detection principles is that the existence of the target makes the fluorescent agent end of the fluorescent probe far away from the quencher so as to realize the recovery of the fluorescent signal. For example, Li et al. Modified fluorescein at one end of the cTnI aptamer sequence, and designed a new fluorescent aptamer sensor based on graphene oxide to detect cTnI. The principle is shown in Figure 1^[26]. Graphene oxide materials can not only adsorb aptamers, but also quench the fluorescence signal. When the cTnI aptamer with fluorescence signal is adsorbed on the surface of graphene oxide, the fluorescence signal is quenched. Because the aptamer has a stronger affinity with cTnI, in the presence of cTnI, the aptamer leaves the graphene oxide and binds to cTnL, and the fluorescence signal is restored. The detection limit of the method was 0. 07 ng/mL and the linear range was 0. 1 ~ 6.0 ng/mL, but the detection of cTnI in serum was greatly affected by the background signal. Large background signal will lead to inaccurate experimental results and misdiagnosis of acute myocardial infarction, so it is necessary to develop detection methods that are less affected by background signal. Wong et al. Used a fluorescent dye, SPM, which turns on the fluorescence of DNA, to provide a fluorescent signal^[27]. They immobilized cTnI antibodies on silica micro-nanoparticles to capture cTnI, and the aptamer of the end-modified hybridization chain reaction triggered chain was bound to cTnL, which hybridized with the other two types of hairpin DNA to start the hybridization chain reaction. The linear DNA amplification unit generated by the reaction was labeled by SPM to produce a strong fluorescence signal, which realized the conversion of cTnI concentration signal to fluorescence signal. The method is less affected by the background signal in the detection of human serum samples, and the detection limit is 0. 20 pg/mL, which is far below the concentration range of cTnI in healthy human serum.

The fluorescence signal can be provided by the fluorescent probe, and the fluorescent agent of the fluorescent probe is far away from the quencher in the presence of the target to achieve the recovery of the fluorescence signal. Based on this principle, L Lü et al. Combined the rolling circle amplification (RCA) with the aptamer, and developed an aptamer-based immuno-RCA combined with fluorescent probe method to detect cTnI^[28]. The cTnI is captured by its antibody, and then binds to the cTnI aptamer that modifies the primer strand of the RCA reaction at the end, and starts RCA under the action of DNA polymerase. The long DNA strand generated by the reaction binds to the fluorescent probe, and the two ends of the fluorescent probe in the hairpin structure are separated so that the fluorescein is far away from the quencher, thus generating an amplified fluorescent signal. The method showed good specificity in the detection of real samples and was less affected by background signals. In addition, the experimental results showed that the detection limit of the method was as low as 7. 24 pg/mL. They developed another detection strategy, designed a new fluorescent probe based on the above detection principle, used graphene oxide as a quencher, modified fluorescein at one end of the probe and fixed it on graphene oxide to quench the fluorescence signal^[29]. Because the fluorescent probe is more compatible with the DNA long chain generated by RCA, when cTnI exists in the reaction system, the fluorescent probe is separated from the graphene oxide and combined with the DNA long chain, the fluorescent signal is restored and amplified, and the detection of the concentration of cTnI is realized.

The aptamer-based fluorescence detection method for cTnI has the advantages of simplicity, high efficiency and low cost, and can provide a reference for clinical application.

The principle of surface-enhanced Raman spectroscopy (SERS) detection is to adsorb the target analyte on a properly rough metal surface. When the molecule is close to the rough metal surface, its vibrational spectrum intensity will be greatly enhanced, and then the Raman spectrometer is used to measure the Raman scattering^[30]. At present, SERS has been widely used in the field of trace molecule detection because of its fast detection speed and high sensitivity^[31]. Mazali et al. Designed a Fe₃O₄@SiO₂@Ag nanoparticle synthesized by a magnetite core with a silicon shell in the middle and a flower-shaped silver layer, and immobilized the aptamer on the silver surface to form a detection system^[32]. The magnetic aggregation provided by the Fe₃O₄ magnetic core and the binding of the Ag tip induced the generation of a large number of hot spots, which enhanced the SERS response of the substrate. This detection system has the advantages of high sensitivity and fast detection speed, but it is easily interfered by other molecules, so it still needs to optimize and improve the detection method before it can be used for the detection of actual samples. Li et al. Developed a tag-based SERS detection strategy^[33]. The Raman signal molecule was selected as CBBG, which does not need to be modified on the protein molecule by chemical bonds, thus optimizing the complex and time-consuming modification process. In this detection strategy, cTnI aptamer was immobilized on magnetic nanoparticles to make a magnetic capture probe. When cTnI was added to the reaction system, the capture probe separated and enriched cTnL, and CBBG was added to combine with cTnL to provide an enhanced SERS signal. The results showed that the detection limit of this strategy was 5. 50 pg/mL, and the linear range was 0. 01 ~ 100 ng/mL, which could be used for the detection of cTnI in human serum. Kim et al. Proposed a method for detecting cTnI by immobilizing an aptamer on an atomically flat gold nanoplatform^[34]. They developed an atomically flat gold nanoplate for immobilizing the cTnI primary aptamer. In the presence of the target, the secondary aptamer modified with gold nanoparticles and Raman dye is combined with the target to form a sandwich structure, which can provide a strong SERS signal at the nanogap between the nanoparticles and the nanoplate, and convert the cTnI concentration signal into a SERS signal. Experiments show that the detection limit of this strategy in serum is 2.4 pg/mL, which has potential diagnostic ability.

Surface-enhanced resonance Raman scattering (SERRS) occurs when the chromophore energy of the analyte is close to the excitation frequency used to excite plasmons and generate SERS. Tu et al. designed a method for aptamer-based cTnI detection on a paper fluid platform in combination with SERRS. The paper platform has five regions, and the detection principle is shown in Figure 2^[35][36]. The aptamer functionalized SERRS active particles are stored in the binding pad in advance, the sample solution is introduced into the sample pad, after the running buffer is added, the cTnI and the SERRS active particles flow to the test line area together to be combined with the secondary aptamer on the test line area to form a sandwich structure, and the redundant SERRS active particle is combined with the DNA strand in the control line area. The increase of cTnI concentration will increase the number of SERRS active particles in the test line area, and the SERRS signal will increase accordingly. Measuring the SERRS signal in the test line area can quantify the cTnI concentration. SERRS can provide a signal 10 to 100 times that of SERS, which makes this method more sensitive, but the detection time of this method is longer and the detection range is narrower, so it is still necessary to find a better optimization scheme to solve the above problems.

Electrochemiluminescence (ECL) is a new technology combining electrochemistry and chemiluminescence, which is produced by high-energy electrons generated on the surface of the electrode during the emission of excited state photons formed in the transfer process.The biosensing principle is to detect the interaction between the biorecognition molecule and the analyte through the ECL emission change related to the ECL active substance. The detection method based on ECL has the advantages of simple equipment, short response time and low background signal, and is used for the quantitative detection of cTnI^[37⇓~39]. In recent years, semiconductor quantum dots, carbon materials and metal nanoclusters have been widely used in ECL system as luminescent materials^[40]. Due to the aggregation-induced ECL phenomenon and the giant ECL characteristics of iridium-based complexes, cyclometalated iridium (III) -polyvinylpyridine polymer (CIPNP) showed higher intensity than classical ECL luminophore Ru(bpy)₃²⁺. Amini et al. Developed an ECL aptasensor to detect cTnI in combination with CIPNP, and the principle is shown in Fig. 3^[41]. They used aptamer-modified gold nanoparticles, CIPNP and nitrogen-doped graphene modified electrodes to increase the load capacity and conductivity of the ECL aptamer sensor. The specific binding of cTnI with the aptamer led to the detachment of the aptamer from the electrode surface, thus enhancing the ECL signal. This principle was used to convert the response signal and realize the sensitive detection of cTnI. The method combines CIPNP and other materials to improve the ECL strength, the conductivity and load capacity of the sensor, and the sensitivity of the sensor is greatly improved. Jin et al. Then prepared a sandwich-type ECL sensor to detect cTnI using CdS quantum dots (QDs) as ECL emitter and AuNPs as plasma source^[42]. CdS QDs were immobilized on the electrode, and carboxyl groups were generated and activated on the surface of QDs by reaction for binding to Tro4 aptamer, and mercaptoethanol (MCH) covered the nonspecific binding site. After adding the sample solution containing cTnI, the Tro4 aptamer, the Tro6 aptamer modified by AuNP and cTnI are combined to form a sandwich structure. The interaction between the luminophor and the gold nanoparticles leads to the resonance interaction between the excited ECL luminophors, realizes the surface plasmon enhanced electrochemiluminescence, and completes the ultrasensitive detection of cTnI. The results showed that the detection limit of this strategy was as low as 0. 75 fg/mL, and the linear detection range was 1 fg/mL ~ 10 ng/mL, which improved the sensitivity again compared with the previous method. However, the detection time of this method is as long as several hours, which is not conducive to clinical application, and the method needs to be optimized to shorten the detection time.

Tu et al. Used luminol /H₂O₂ as a luminescent probe of ECL, and in-situ generated mesoporous silica membrane (MSF) with vertically aligned nanochannels on indium tin oxide (ITO) coated glass by reaction, and these nanochannels of MSF were used to pass the luminescent probe^[43]. When the cTnI aptamer is modified at the edge of the nanochannel mouth, the combination of cTnI and the aptamer will cause the channel to be blocked and hinder the passage of the luminescent probe, thus causing the ECL signal to decrease and the EIS signal to increase. Using this principle, cTnI can be quantitatively analyzed by ECL and EIS in parallel, and the linear detection range is 0. 05 pg/mL ~ 10 ng/mL. The main advantage of the sensor is that it can quantify cTnI in parallel through ECL and EIS signal responses, which makes the detection results more reliable and accurate, but the response speed of the sensor is still at a slow level, and the detection time is up to 1. 5 H. In addition to the above methods, the researchers also designed a ratiometric sensing strategy for cTnI detection combined with electrochemiluminescence^[44,45].

Methods based on optical detection of cTnI also include colorimetry and SPR^[46][47]. Through the above studies, it can be seen that these methods have the advantages of high sensitivity, good specificity and good selectivity, which realize the sensitive detection of cTnI, and also provide a reference for the subsequent development of new optical detection methods.

EIS is often used to study interfacial electrochemical phenomena, and EIS detection using a target capture probe modified electrode is a reliable and stable method^[53,54]. At present, researchers have developed many EIS-based electrochemical aptamer sensing platforms for the detection of cTnI, which have the advantages of easy operation and miniaturization^[55]. The detection principle is that the capture of cTnI by the specific aptamer immobilized on the electrode surface will lead to the change of the impedance of the electrode surface, and the impedance will change with the change of cTnI concentration^[56]. Modification of the electrode surface with materials with good electrochemical performance is helpful to improve the detection performance of the sensor. Zheng et al. Modified the MoS₂ on the electrode and fixed the cTnI aptamer on it. When cTnI was added, due to the stronger binding between cTnL and aptamer, the aptamer was separated from the electrode surface and specifically bound to cTnL, resulting in impedance changes, which realized the detection of cTnI^[57]. However, due to the instability of van der Waals force, MoS₂ will have serious re-stacking, resulting in the reduction of active sites and poor conductivity when combined with other materials, which will affect the electrochemical performance. To overcome these shortcomings, a composite material CA-MoS₂ composed of cellulose acetate (CA) and molybdenum disulfide (MoS₂) was designed for the development of cTnI electrochemical aptasensor, which has a large number of exposed active sites and good electron transfer properties^[58]. The sensitive detection of cTnI was achieved by modifying CA-MoS₂ on the electrode and improving the electrochemical performance combined with the EIS method.

AuNPs have also been used in the development of electrochemical sensors due to their advantages such as large surface area and size controllability. Kitte et al. designed an electrochemical detection platform for cTnI based on EIS in combination with AuNPs, and the principle is shown in Figure 4^[59]. Thiol groups were introduced on the surface of indium tin oxide (ITO) electrode after treatment, which was used to bind AuNPs. The cTnI aptamer modified by thiol at one end is bound to the AuNPs to capture cTnI, and the binding of the aptamer to the AuNPs leads to an increase in the impedance of the sensor in the presence of cTnL. EIS analysis showed that the detection limit was as low as 0. 055 pg/mL and had a wide linear range (between 0. 1 pg/mL and 10 ng/mL).The detection results of this strategy in human serum samples were satisfactory, and it is expected to be used for the detection of real samples in the future.

The above cTnI electrochemical aptasensor realizes the sensitive conversion of concentration signal to electrochemical signal through EIS. The introduction of materials with excellent electrochemical performance amplifies the electrochemical signal to improve the sensitivity. In addition, the sensor also shows excellent selectivity, achieving a low detection limit and a wide detection range.

DPV is also a commonly used biomarker quantitative analysis method in electrochemical detection. With the increase of target analyte, the peak current changes, thus realizing the conversion from analyte concentration signal to current signal^[60]. Because the single-stranded DNA aptamer is prone to nonspecific adsorption and aggregation on the electrode surface, the binding of cTnI to the aptamer is hindered, and the sensitivity of the detection is affected. The DNA nano-tetrahedron (NTH) can inhibit the entanglement of aptamers and firmly adhere to the electrode surface due to its unique structure. Sun et al. Designed an electrochemical dual-aptamer biosensor in combination with NTH, and the principle is shown in Figure 5^[61]. Firstly, the two aptamers were modified on the surface of bimetallic Cu @ Au nanoparticles modified magnetic metal-organic framework Fe₃O₄@UiO-66(Fe₃O₄@UiO-66/Cu@Au) to obtain non-enzymatic nanoprobe 1 (NP1), and the cDNA complementary to the two aptamers was modified on the Cu @ Au nanoparticles to form non-enzymatic nanoprobe 2 (NP2). The aptamer modify at one end of that NTH captures the cTnI, the aptamer on the NP1 is combine with the cTnI, and the NP2 is combined with the NP1 through base complementary pairing to form the cluster-based nanoprobe, which is used for catalytic reaction to amplify electrochemical signals and improve sensitivity. Finally, the quantitative detection of cTnI was realized by DPV. The higher the concentration of cTnI, the higher the peak current of DPV. The results showed that the detection limit was 16 pg/mL. The sensitivity was improved by optimizing the design of the nanocatalytic probe and modifying the NTH modified aptamer, and the detection limit was as low as 7. 5 pg/mL^[62].

Generally speaking, only aptamer binding to cTnI is not enough to produce enough signal intensity for quantitative analysis, so nanomaterials with signal amplification have been developed to improve the performance of electrochemical aptasensor.Jin et al. Assembled Au nanoparticles on the surface of indium oxide (In₂O₃) and developed a cubic Au/In₂O₃ nanomaterial, which significantly improved the conductivity^[63]. The material is modified on the electrode and used for the immobilization of the aptamer, and when the cTnI is combined with the aptamer, the cTnI is negatively charged and hinders the electron transfer on the surface of the electrode, so that the DPV peak current is reduced, and the signal conversion is realized. This method simplifies the experimental operation and shortens the detection cycle, and the detection of cTnI can be completed in only 10 min. The detection limit is 0. 06 ng/mL and the linear detection range is 0. 1 ~ 1 000 ng/mL. In addition, Guo et al. Designed a composite nanomaterial of copper nanowires (CuNWs), redox graphene (rGO) and MoS₂, and Yuan et al. Designed a composite nanomaterial of silver nanoparticles (AgNPs)/MoS₂/rGO, both of which were used for the development of cTnI electrochemical aptasensor^[64][65]. Wang et al. Proposed a new strategy to modify ferrocene covalent organic framework nanosheets (Fc-COFNs) on a gold electrode, and the cTnI aptamer attached to the Fc-COFNs played a shielding role, resulting in a significant reduction in the electrochemical signal^[66]. After the solution to be detected is added, the aptamer is separated from the surface of the Fc-COFNs due to the stronger binding between the cTnI and the aptamer, the electrochemical signal is restored, the DPV peak current is increased, and the quantitative detection of the cTnI is realized. The results showed that the method had excellent performance, the detection limit was 2. 6 fg/mL, and the sensitivity was very high. However, if it is applied to the detection of real samples, the detection time still needs to be shortened, and the experimental operation can be optimized and the experimental steps can be simplified to achieve rapid detection.

SWV is a general voltammetry technique often used in areas such as analytical applications^[67]. In analytical applications, SWV demonstrates shorter analysis times and the ability to significantly reduce capacitive currents compared to other voltammetric methods^[68]. An electrochemical aptamer sensing platform based on SWV and nanomaterials has shown excellent performance in cTnI quantitative analysis. Ban et al. Designed an electrochemical sensing platform based on SWV using ferrocene-modified silica nanoparticles (Fc-SiNPs)^[69]. Fc-SiNPs as an electrochemically active probe for electron transfer. In the absence of cTnI, the aptamer self-assembled monolayer allowed Fc-SiNPs to enter the electrode surface to generate a large current signal, while in the presence of cTnI, the specific binding of aptamer and cTnI prevented Fc-SiNPs from entering the electrode surface and reduced the current signal. Based on this principle, SWV was used for quantitative determination, and the oxidation peak current decreased in different degrees according to the concentration of cTnI. The results showed that the detection limit of the platform in buffer was 24 pg/mL. A terminal deoxynucleotidyl transferase (TdT) -mediated signal amplification strategy was used to design the electrochemical sensor, and the principle is shown in Fig. 6^[70]. Probe 2 (P2) was modified on the gold electrode, and the cTnI aptamer chain was bound to probe 1 (P1). When cTnI was added, the aptamer was dissociated from P1 and bound to cTn1, and the free P1 was bound to P2 to form a DNA hybrid double strand. In the presence of TdT and dTTP, TdT mediates the extension of P1 to form an ultra-long polythymine nucleic acid strand (polyT), which is used to bind a large amount of polyadenine strand (polyA) modified methylene blue (MB) to the electrode surface. Because MB is an electron transfer mediator, the electrochemical signal is amplified and the sensitivity of cTnI detection is improved. SWV was used for quantitative analysis, and cTnI was successfully detected in human serum, urine and saliva.

Salama et al. Employed laser etched graphene (LSG) electrode with easy surface modification and fabrication and modified with novel ferrite zinc nanoparticles (ZnFe₂O₄NPs), which significantly improved the sensitivity and electrocatalytic activity^[71]. The thiol-modified DNA aptamer was immobilized on the electrode surface, and the aptamer combined with cTnI to block the diffusion of the redox probe to the electrode surface, resulting in a decrease in the peak current. The SWV was used to measure the peak current before and after the addition of cTnI to complete the quantification of cTcI. Experimental analysis shows that this strategy is promising for integration into point-of-care (POC) devices for the detection of cTnI.

In addition to the above methods, researchers have developed other electrochemical detection platforms. For example, Ban et al. Developed a sandwich biosensor using amperometry^[72]. The electrode surface was modified by electrodeposition of gold nanoparticles and electropolymerization of conductive polymer, and the aptamer Tro4 was immobilized on the electrode surface, and hydrazine was modified at one end of the aptamer Tro6 as a detection probe. In the presence of cTnI, the three were combined to form a sandwich structure. This strategy enables the quantification of cTnI by detecting the amperometric signal generated by the catalytic reaction between hydrazine and H₂O₂. Villalonga et al. Constructed a sandwich-type amperometric aptamer sensor by combining the amino-modified aptamer (Apt-NH₂) and aptamer-peroxidase conjugate (Apt-HRP) with the nanomaterial carboxyethylsilanetriol modified graphene oxide (CES-GO) as the transducing element modified electrode^[73]. In the presence of cTnI, Apt-HRP and Apt-NH₂ formed a sandwich structure, and HRP increased with the increase of cTnI. Under the catalysis of HRP, the current signal is amplified, the concentration signal is converted into a current signal, and finally the signal is measured by amperometry. After that, Lan et al. Designed an Au modified zirconium-based conductive carbon (Au/Zr-C) modified electrode, which reduced the background signal, improved the electrochemical performance and increased the sensitivity^[74]. In addition, they designed a snowflake-like PtCuNi ternary metal alloy as a catalyst, which further improved the sensitivity, with a detection limit of 1.24 fg/mL, showing excellent performance in the quantitative analysis of cTnI. Interdigitated electrodes were also used to construct an electrochemical sensing platform for cTnI. Gopinath et al. Immobilized gold nanoparticles (GNPs) modified aptamers on the interdigitated electrodes to capture cTnI, and realized the conversion of response signals through electroanalysis, which improved the sensitivity compared with pure aptamers as capture probes^[75]. Electrochemical detection has the advantages of low cost, simple equipment and fast response, and has great potential in the research and development of miniaturized and portable equipment^[76]. However, electrochemical aptamer biosensors usually need to modify the aptamer on the electrode surface to form a sensitive functional coating, which is easy to fall off under biological fluids, dry air, voltage pulses and other factors, which limits the wide application of electrochemical aptamer biosensors^[77]. Aptamer sensors based on optical signals are not affected by the operation of aptamer fixation and modification. Compared with electrochemical signal sensors, they have better stability and higher sensitivity. At present, some optical biosensors have entered the market, but most of them are more expensive.This is because the sensitivity of optical signal biosensors depends on more complex molecular systems. It will be one of the research directions of optical signal biosensors to reduce the dependence on complex molecular reaction systems by developing optical biosensors based on new principles and methods^[78]. Therefore, there is still much room for the development of aptamer sensors based on electrochemical and optical signals for home diagnosis of AMI.