Trends and frontiers in signal amplification for aptamer-based tumor detection:A bibliometric analysis

BACKGROUND Malignant tumors are one of the leading causes of death worldwide,imposing a substantial economic and social burden.Early detection is the key to improving cure rates and reducing mortality rates,which requires the development of sensitive early detection technologies.Signal amplification techniques play a crucial role in aptamer-based early detection of tumors and are increasingly garnering attention from researchers.AIM To investigate the current research status,developmental trajectories,and hotspots in signal amplification for aptamer-based tumor detection through bibliometric analysis.METHODS English publications pertaining to signal amplification in aptamer-based tumor detection were retrieved from the Web of Science Core Collection database.VOSviewer and CiteSpace software were employed to analyze various information within this field,including countries,institutions,authors,co-cited authors,journals,co-cited journals,cited references,and keywords.RESULTS A total of 757 publications were included in this study.China accounted for 85.47%of all publications,with Nanjing University(China)emerging as the institution with the highest publication output.The most influential authors and journals were Hasanzadeh M.from Iran and"Biosensors and Bioelectronics",respectively.Exosomes and carcinoembryonic antigen(CEA)stood out as the most researched tumor-related molecules.Currently,the predominant signal amplification technique,nanomaterial,and signal transduction method were identified as hybridization chain reactions,gold nanoparticles,and electrochemical methods,respectively.Over the past 3 years,exosomes,CEA,electrochemical biosensors,and nanosheets have emerged as research hotspots,exhibiting a robust burst of intensity.CONCLUSION This study is the first bibliometric analysis of literature on signal amplification in aptamer-based tumor detection and elucidates the current status,hotspots,and prospective research directions within this realm.Additionally,it provides an important reference for researchers.

Current trends in nanomaterials-mediated biosensing platforms and signal amplification strategies for antibiotics detection in dairy products

Dairy products have become one of the most prevalent daily foods worldwide,but safety concerns are rising.In dairy farming,unscrupulous traders misuse antibiotics to treat some diseases such as mastitis in cows,leading to antibiotic residues in dairy products.Rapid,sensitive,and simple detection methods for antibiotic residues are particularly important for food safety in dairy products.Traditional detection technology can effectively detect antibiotics,but there are defects such as complicated pre-treatment and high cost.Biosensors are widely used in food safety due to fast detection speed,low detection cost,strong anti-interference ability,and suitability for the field application.Nevertheless,these sensors often fail to trigger the signal conversion output due to low target concentration.To cope with this issue,some high-efficiency signal amplification systems can be introduced to improve the detection sensitivity and linear range of biosensors.In this review,we focused on:(i)Sources and toxicity of major antibiotics in animal-derived foods.(ii)Nanomaterial-mediated biosensors for real-time detection of target antibiotics in animal-derived foods.(iii)Signal amplification techniques to increase the sensitivity of biosensors.Finally,future prospects and challenges in this research field are discussed.

Personal glucose meters coupled with signal amplification technologies for quantitative detection of non-glucose targets:Recent progress and challenges in food safety hazards analysis

Ensuring food safety is paramount worldwide.Developing effective detection methods to ensure food safety can be challenging owing to trace hazards,long detection time,and resource-poor sites,in addition to the matrix effects of food.Personal glucose meter(PGM),a classic point-of-care testing device,possesses unique application advantages,demonstrating promise in food safety.Currently,many studies have used PGM-based biosensors and signal amplification technologies to achieve sensitive and specific detection of food hazards.Signal amplification technologies have the potential to greatly improve the analytical performance and integration of PGMs with biosensors,which is crucial for solving the challenges associated with the use of PGMs for food safety analysis.This review introduces the basic detection principle of a PGM-based sensing strategy,which consists of three key factors:target recognition,signal transduction,and signal output.Representative studies of existing PGM-based sensing strategies combined with various signal amplification technologies(nanomaterial-loaded multienzyme labeling,nucleic acid reaction,DNAzyme catalysis,responsive nanomaterial encapsulation,and others)in the field of food safety detection are reviewed.Future perspectives and potential opportunities and challenges associated with PGMs in the field of food safety are discussed.Despite the need for complex sample preparation and the lack of standardization in the field,using PGMs in combination with signal amplification technology shows promise as a rapid and cost-effective method for food safety hazard analysis.

Influence of coupling asymmetry on signal amplification in a three-node motif

The three-node feedforward motif has been revealed to function as a weak signal amplifier. In this motif, two nodes(input nodes) receive a weak input signal and send it unidirectionally to the third node(output node). Here, we change the motif's unidirectional couplings(feedforward) to bidirectional couplings(feedforward and feedback working together).We find that a small asymmetric coupling, in which the feedforward effect is stronger than the feedback effect, may enable the three-node motif to go through two distinct dynamic transitions, giving rise to a double resonant signal response. We present an analytical description of the double resonance, which agrees with the numerical findings.

Chromosomal Localization of Genes bz1,bz2 in Maize by Using Ultra-sensitive FISH with Tyramide Signal Amplification(TSA-FISH)

It has been reported that endosperm undergoes programmed cell death (PCD) during maize kernel development.Both bz1 (bronze ) and bz2 are anthocyanin biosynthetic genes,and related to development of aleuronic layer of maize seeds.Tyramide signal amplification fluorescence in situ hybridization (TSA FISH) is a novel and high sensitive FISH technique,which is suitable for routine application in plant cytogenetic research.Using this technique,we physically mapped the bz1 gene onto the short arm of chromosome 9 and the long arm of chromosome 1;the percentage distances from centromere to hybridization site were 40.2,75.4 respectively,and the bz2 onto the long arm of chromosome 1 and the short arm of chromosome 5;the percentage distances from centromere to hybridization site were 21.6,15.3 separately.The TSA FISH techniques of small low copy DNA sequences for plants are discussed.

Optical Switching and Digital Signal Amplification Using an Optical Fiber Grating OBD

It is proposed that an optical fiber grating bistability device may be used for an all optical switching or an all optical digital signal amplifier with low power and high speed. The principle, characteristic and paremeter are analysed, and some design ideas are given.

Sensitive detection of microRNAs using polyadenine-mediated fluorescent spherical nucleic acids and a microfluidic electrokinetic signal amplification chip

The identification of tumor-related microRNAs(miRNAs)exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications.Therefore,we developed a sensitive and efficient biosensor using polyadenine(polyA)-mediated fluorescent spherical nucleic acid(FSNA)for miRNA analysis based on strand displacement reactions on gold nanoparticle(AuNP)surfaces and electrokinetic signal amplification(ESA)on a microfluidic chip.In this FSNA,polyA-DNA biosensor was anchored on AuNP surfaces via intrinsic affinity between adenine and Au.The upright conformational polyA-DNA recognition block hybridized with 6-carboxyfluorescein-labeled reporter-DNA,resulting in fluorescence quenching of FSNA probes induced by AuNP-based resonance energy transfer.Reporter DNA was replaced in the presence of target miRNA,leading to the recovery of reporter-DNA fluorescence.Subsequently,reporter-DNAs were accumulated and detected in the front of with Nafion membrane in the microchannel by ESA.Our method showed high selectivity and sensitivity with a limit of detection of 1.3 pM.This method could also be used to detect miRNA-21 in human serum and urine samples,with recoveries of 104.0%-113.3% and 104.9%-108.0%,respectively.Furthermore,we constructed a chip with three parallel channels for the simultaneous detection of multiple tumor-related miRNAs(miRNA-21,miRNA-141,and miRNA-375),which increased the detection efficiency.Our universal method can be applied to other DNA/RNA analyses by altering recognition sequences.

一种压阻式传感器信号调理电路的设计

由于压阻式MEMS传感器输出信号极其微弱,极易受到测试环境的噪声干扰,还需要外接调理电路,为了提升信号的采集精度,提出一种压阻式传感器信号ASIC调理电路的设计方案,实现输出信号的放大、滤波功能。测试结果表明,调理电路可以在10~200倍的范围内调节增益,-0.5 dB截止频率调节范围覆盖0.1~20 kHz;低频范围内,芯片的等效噪声为45 nV/√Hz。将调理电路与传感器相结合,改进的测试系统响应速度快,滤波效果更好,测试精度优于5%,传感器非线性为5.4%。同时,调理电路的大小和体积也很小,功耗低,对后续继续研究传感器测试系统有重要意义。

强信号全覆盖下反射式强度型传感器信号调制设计

反射式强度型传感器在强信号全覆盖环境下常常受到干扰和影响,导致传感器信号的质量下降甚至失真,给后续的信号处理和数据分析带来了困难。对此,提出强信号全覆盖下反射式强度型传感器信号调制方法。首先,判断强信号全覆盖环境下传感器信号的稀疏性,并根据环境的干扰因素建立信号的观测矩阵,通过优化算法计算出稀疏向量的估计值,使用稀疏向量的估计值对观测信号进行补偿,得到补偿后的信号;然后,应用正交锁相放大技术,将补偿后的信号与严格正交的两路参考信号相乘,提高信噪比,获得增强后的信号;最后,利用连续相位多支路调制方法,对增强后的传感器信号展开比特信息分离、二维信号映射与载波相位调制操作,完成信号调制。实验结果表明,所提方法可扩展性强、稳定性高且抗干扰能力强。

基于DNA步行器的传感器技术在食品安全检测中的研究进展

随着DNA纳米技术的快速发展,各种结构和功能的DNA分子被用于构建具有动态行为的可编程纳米机器。其中,DNA步行器因其能够借助驱动力在预定轨道上自主、逐步移动以产生级联信号放大的优势,成为了生物传感、生物成像以及药物递送等领域日益增长的研究热点,在食品污染物快速超灵敏检测方面展现出巨大的应用潜力。本综述首先简要介绍了DNA步行器的基本原理,并着重阐述了提升DNA步行器行走效率的策略,然后总结了其在食品安全检测中的应用,最后对DNA步行器未来研究方向进行了展望,为推动其实际应用提供了理论指导。

Simple Enzyme-Free Biosensor for Highly Sensitive and Selective Detection of miR-21 Based on Multiple Signal Amplification Strategy

Due to the fact that most microRNAs are small in size,low abundance in biological samples,homologous sequence among family members,and protein enzymes-based strategies display limited practical applications,therefore,we reported a simple enzyme-free DNA sensor for microRNA detection utilizing a multiple signal amplification strategy.The sensing system termed as C-CHA-HCR includes six hairpin DNA reactants that are metastable on account of intramolecular hybridization.The DNA hairpin reactants are opened and hybridized with the corresponding complementary DNA strand in the presence of miR-21 via toehold-mediated CHA,HCR reaction,and circulation between CHA and HCR,resulting in a hugely amplifying signal output.Without introducing external protein enzymes,this sensing system showed highly sensitive and selective on the detection of miR-21.A linear response range of miR-21 from 25 pmol/L to 1 nmol/L with a limit of detection(LOD)of 1.8 pmol/L was obtained.This promising biosensor was successfully applied to the detection of microRNA in human serum samples with acceptable recovery rates,suggesting the potential applications in disease diagnosis,treatment,and prognosis.

采用多丝正比室读出的屏栅电离室能量分辨研究

搭建了一个基于多丝正比室读出的屏栅电离室探测器,使其保留屏栅电离室屏蔽特性的同时具备雪崩放大功能,通过在探测器内部对原初电离信号进行预放大,以提高信噪比,改善探测器的能量分辨率。利用241Am源详细测试了探测器在不同气压、沉积能量、阳极丝径时能量分辨率及增益随阳极电压的变化关系。探测器最佳能量分辨对应的工作电压与入射粒子在漂移区中沉积的能量有关,能量沉积越小,对应的最佳工作电压越高,探测器的增益越大。对于5.486 MeV的241Am α粒子源的能量分辨率可达1.45%。

AlGaN/GaN HEMT小信号放大电路设计及放大增益预测

采用计算机辅助设计技术(TCAD)对AlGaN/GaN高电子迁移率晶体管(HEMT)器件进行了仿真,并利用Multisim设计了AlGaN/GaN HEMT器件的低频小信号放大电路.由于GaN材料的宽带隙和高载流子迁移率,HEMT器件可以在空间科学应用中取代Si基MOSFET.TCAD的仿真结果通过与测试结果的比较进行了修正.通过Multisim仿真结果与搭建的AlGaN/GaN HEMT共源共栅放大电路的测试结果对放大电路的放大特性进行了验证.以此为基础,利用TCAD模拟改变了结构参数的器件特性并采用改进了结构参数的AlGaN/GaN HEMT设计共源共栅放大电路.仿真结果表明,该放大电路在低频和室温下的电压放大能力可达6 200倍.

压电MEMS振动传感器调理电路设计与实现

针对铌酸锂单晶薄膜的压电MEMS振动传感器输出电荷信号微弱而难以采集的问题,设计了一种基于集成运放芯片TLE 2064 CDR的信号调理电路。该电路由电荷-电压转换电路(Q-V)、电压放大电路、前置低通滤波电路和后置高通滤波电路构成,旨在实现微弱信号的采集。此外,利用ACT 2000振动台进行振动实验,通过标准电荷放大器和设计的信号调理电路对压电MEMS振动传感器测试。测试结果表明,所设计的信号调理电路与标准电荷放大器的输出有较好的一致性,可以满足5~130 pC的宽输入电荷的采集。当加载加速度范围为5~20 g时,输出电荷和输入加速度之间的线性度好;在输入加速度5 g,工作频率范围为50~2000 Hz时,输出电荷偏差控制在±1.6 pC内,具有很好的一致性。综上所述,该电路具有集成度高,灵敏度好等特点,在微弱信号采集方面具有很好的应用前景。

全国产化微弱信号调理电路

为更好地处理微弱信号,提出一种新型的多通道信号前端调理模块。该模块不仅具有可编程增益功能,而且还整合了带通滤波器。在保证高输入阻抗和低噪声等关键性能的同时,提出一种全面而创新的调理模块设计方案。该方案的核心是采用可编程增益放大电路,显著提高了模块在放大各类微弱信号时的适应性。此外,利用HC595系列芯片,实现了对增益的精确调控。该放大电路具备26 dB的固定增益和0~84 dB的可调增益范围,工作带宽设定在380~420 kHz。经过系统性能测试,结果表明该调理电路成功满足了设计目标的各项要求。

基于DNAzyme辅助信号放大的荧光检测APE1

利用脱氧核酶(DNAzyme)辅助放大荧光信号,发展了一种简便快速无嘌呤/无嘧啶内切酶(APE1)的高灵敏度检测策略。验证了实验可行性,对反应时间、反应温度进行了优化,在最优条件下对目标物APE1进行了检测,检测限为3.0×10^(-4)U·mL^(-1),并证明了本实验具有良好的选择性。

表面增强拉曼散射光谱在miRNAs检测中的研究进展

表面增强拉曼散射(SERS)因其灵敏度高、非侵入性、多路检测等特点,已广泛应用于生物医学检测。研究发现微小核糖核酸(miRNAs)的异常表达与多种疾病有关,miRNAs已成为一种新型的生物标志物。开发简单、灵敏、可靠的miRNAs检测方法,对miRNAs的生物学功能研究、医学诊断、疾病治疗和靶向药物研究具有重要意义。目前,与核酸信号放大策略相结合的纳米SERS探针,用于miRNAs检测表现出较高的灵敏度。然而实际样本中成分复杂,易产生背景信号,干扰检测结果;分离纯化过程繁琐,增加了检测时间。近年来,研究者们通过结合其他技术来优化检测,提高样本检测通量、简化操作、减少分析时间、提高分辨率。该论文主要介绍了基于SERS技术的miRNAs检测方法的最新进展,讨论了技术融合的优势与必要性,并总结了基于SERS技术的miRNAs检测用于临床检测还存在的问题,旨在为设计新型快速灵敏可靠的miRNAs SERS检测平台提供参考。

基于核酸适体的电化学生物传感研究

核酸适体是一类经由指数富集的配体系统进化(SELEX)技术在体外筛选获得的单链寡核苷酸片段,由于具有可人工批量合成、价格低廉、易于功能化修饰、特异性强、亲和力高、免疫原性低、批间差异小、热稳定性好等优良特性,在分析化学、疾病治疗以及生物医学研究等诸多领域备受关注。结合代表性案例,该文综述了核酸适体在电化学生物传感领域的应用。首先简要概述了核酸适体及电化学适体传感器的特点,分类阐述了电化学适体传感器在小分子化合物、蛋白质、外泌体、循环肿瘤细胞(CTCs)以及病原微生物检测中的应用,并重点介绍了相关检测方法的原理、分析特性以及所应用的信号放大策略,最后对电化学适体传感器的发展进行了展望。

管道阴极保护电流内检测硬件系统设计

针对传统外检测方法难以在某些特殊管段进行阴极保护电流检测的难题,通过管道内检测法实现管道电流参数的采集,消除了管道阴极保护电流检测盲区。给出了管道阴极保护电流硬件系统设计方案,包括电流放大电路设计、信号转换电路设计、电源方案设计。进行了管道阴极保护电流硬件系统实验测试,获得了阴极保护电流—电压标定曲线。测试结果表明,硬件系统可满足设计要求,为后续管道阴极保护内检测现场应用提供了硬件支持和理论依据。