Nature Communications
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2025
·Vol. 16
·期 1
·1-14
·
IF 15.7
Hu Hao,Guo Songcheng,Li Yiyuan,Dong Kejun,Lu Yan,Ye Keyi,Li Longjie,Zhou Xiaoyu,Cheng Liming,Xiao Xianjin
Detecting small molecules is pivotal across fields like clinical diagnostics, environmental monitoring, and food safety. The CRISPR-Cas12a system, known for its simplicity and sensitivity, offers a promising basis for small molecule detection. However, current CRISPR-based detection methods face challenges, including complex design requirements, high background noise, and limited adaptability to different targets. In our study, we introduce the SBS-Cas system, leveraging a split crRNA mode to induce spatial hindrance on the scaffold strand through molecular binding. This approach prevents the assembly with Cas12a, effectively masking its trans-cleavage activity. By introducing small molecules that competitively bind to the macromolecule, we eliminate this spatial hindrance, activating Cas12a. Our results demonstrate high sensitivity, versatility, and adaptability in small molecule detection across multiple reactions, with successful intracellular imaging and responsive fluctuations in complex environments underscoring the system’s robustness. This innovative CRISPR-Cas12a-based approach establishes a low-background, highly sensitive platform for small molecule detection. SBS-Cas promises not only to enhance tools for clinical, environmental, and food safety applications but also to advance CRISPR research, providing insights and expanding possibilities in molecular detection science.
研究领域:
分子生物学
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临床诊断
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环境科学
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食品安全
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产品关联
DOI
PubMed
高影响因子
Micromachines
·
2018
·Vol. 9
·期 6
·274
·
IF 2.222
Zihao Li,Chenggang Zhu,Zhihe Guo,Bowen Wang,Xiang Wu,Yiyan Fei
The detection of small molecules has increasingly attracted the attention of researchers because of its important physiological function. In this manuscript, we propose a novel optical sensor which uses an optofluidic microbubble resonator (OFMBR) for the highly sensitive detection of small molecules. This paper demonstrates the binding of the small molecule biotin to surface-immobilized streptavidin with a detection limit reduced to 0.41 pM. Furthermore, binding specificity of four additional small molecules to surface-immobilized streptavidin is shown. A label-free OFMBR-based optical sensor has great potential in small molecule detection and drug screening because of its high sensitivity, low detection limit, and minimal sample consumption.Keywords:label-free sensor;optofluidic microbubble resonator;detection of small molecules
研究领域:
生物医学工程
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光学传感
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分子生物学
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DOI
PubMed
高影响因子
Analytical Methods
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2022
·Vol. 14
·期 11
·1140-1147
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IF 3.532
Tuqiang Li,Yulan Wang,Yanan Zhang,Guobao Zhou,Lei Li
An entropy-driven DNA circuit offers an efficient means of sensitive analyte detection with signal amplification. In this article, we rationally engineered an aptamer-based entropy-driven signal-off DNA circuit for colorimetric detection of small molecules. The proposed signal-off DNA circuit is activated by target small molecule binding to drive the collapse of G-quadruplex DNAzyme, accompanied by the colour change of the detection solution from dark blue to light blue. Entropy-driven recycling hybridization significantly magnified the input signal of the target small molecule. Such an assay enables naked-eye detection of adenosine triphosphate and oxytetracycline at concentrations as low as 0.5 μM and 1 μM respectively. Moreover, when compared with the signal-on DNA circuit, the entropy-driven signal-off DNA circuit for colorimetric detection has two advantages. Firstly, unlike in the signal-on DNA circuit, the unavoidable formation of waste complexes in the absence of a target in the signal-off DNA circuit has no influence on target detection performance as its background signal is only determined by the substrate complex. Secondly, the signal-on DNA circuit cannot distinguish false-positive signals generated by invasive catalysts (e.g., HRP, serum, Fe3O4), while the signal-off DNA circuit can distinguish those signals as undesired signals. Overall, the signal-off DNA circuit affords a novel strategy for sensitive and accurate detection of small molecules.
研究领域:
生物化学
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分子生物学
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DOI
PubMed
高影响因子
ACS Sensors
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2022
·
IF 9.618
Ting Liu,He Ding,Jianwei Huang,Chengsen Zhan,Shouyu Wang
This paper first reports a liquid-core hydrogel optical fiber fluorescence probe. It is composed of a liquid core, a high-refractive-index hydrogel fiber core, and a low-refractive-index hydrogel fiber cladding, which is completely different from many existing optical fiber fluorescence probes. The sensing solution with sensitive materials is sealed as a liquid core, and it can sufficiently react with small-molecule targets penetrating through the hydrogel fiber cladding and core, thus inducing variations in the fluorescence signals. These fluorescence signals can be localized and transmitted within the probe and finally collected and quantified for target detection. This proposed probe can be simply and rapidly fabricated and reused, and it was proven to have high sensitivity, accuracy, and selectivity in practical applications. Therefore, this liquid-core hydrogel optical fiber fluorescence probe will enable a novel sensing platform for small-molecule analyte detection that faces on-site detection challenges.
研究领域:
生物医学工程
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光学传感
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分析化学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2020
·
IF 7.1
Lei Peng,Jin Zhou,Guozhen Liu,Lijuan Yin,Siyu Ren,Shuli Man,Long Ma
CRISPR-Cas based detection platform opens up a new avenue for biosensing owing to its programmability , sequence specificity and high base resolution upon nucleic acid targets. In current study, we utilised the target DNA-induced non-specific single-stranded DNA cutting activity ( trans -cleavage) of CRISPR-Cas12a to fabricate an aptamer mediated fluorescent biosensor for sensitive and selective detection of adenosine triphosphate (ATP). In this sensor, we designed an ATP-binding aptamer as the target ssDNA for Cas12a, thereby in the presence of ATP, the ATP-binding aptamer would be occupied by ATP, and less target ssDNA can be processed by Cas12a, which gave rise to an ATP concentration dependent change in fluorescence resulted from trans -cleavage of doubly labeled ssDNA reporter. In this way, we successfully “translated” ATP signals to nucleic acid signals that can be amplified by Cas12a process. The dynamic detection range was from 1 μM to 200 μM and the limit of detection was 400 nM. The entire sample-to-answer time for this biosensor was around 40 min. Overall, this novel biosensor balanced sensitivity, specificity, detection time and ease of use. Our proposed biosensor provided a principle-of-proof for detecting small molecule by using CRISPR-Cas12a system, which would unlock its potential and further its futuristic applications in the field of diagnostics.
研究领域:
分子生物学
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生物传感技术
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诊断学
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DOI
高影响因子
MICROCHIMICA ACTA
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2021
·Vol. 188
·期 1
·1-11
·
IF 5.833
Lv Yuanxia,Qin Xiaohuan,Hu Kun,Huang Yong,Zhao Shulin
A novel matrix-assisted laser desorption/ionization time-of-flight mass spectrometric method (MALDI-TOF MS) for determination of highly sensitive small molecular compounds was developed based on molybdenum disulfide nanosheets hybridized with ultrathin graphitic carbon nitride (MoS 2 /g-C 3 N 4 ) as the matrix. With this approach, the synergistic effects of MoS 2 and g-C 3 N 4 enhance the UV absorption of MoS 2 /g-C 3 N 4 , increase both desorption and ionization efficiency in LDI MS, and induce higher signal-to-noise ratio of analytes when compared with the bare MoS 2 and g-C 3 N 4 matrix in the determination of amino acids, antibiotics, neutral oligosaccharides, uric acid, and polyethylene glycols (PEGs). The detection limits of these small molecular compounds are in the ranges 0.1 to 10 μg mL −1 , 1*10 −3 to 1.0 μg mL −1 , 1.0 to 10 μg mL −1 , and 2*10 −4 μg mL −1 , respectively, and the polydispersity index of these PEGs is less than 1.02. Moreover, high salt tolera`nce and homogeneous deposition on the spot results in good reproducibility. The relative standard deviations (RSDs) of shot-to-shot and spot-to-spot ( n = 15) of these compounds are less than 10.1% and 12.5%, respectively. With MoS 2 /g-C 3 N 4 , the uric acid in complicated biological samples can be directly determined in combination with LDI-TOF MS. Graphical abstract
We synthesized MoS 2 /g-C 3 N 4 nanohybrid as an efficient matrix for MALDI-TOF MS analysis of small molecules as well as quantitative detection of uric acid in human urine.
研究领域:
分析化学
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生物医学
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DOI
高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 8
·1131-1136
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IF 2.378
Yueying Zhang,Dan Gao,Shangfu Li,Weili Wei,Jinshun Lin,Yuyang Jiang
1,5-Diaminonaphthalene functionalized carbon nanodots (DAN-CDs) were explored as a novel matrix for direct detection of small molecules by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) in negative ion mode. By using DAN-CDs as the matrix, we could detect not only biological small molecules such as fatty acids (FAs), amino acids, peptide Gly–Gly and dopamine, but also anticancer drug erlotinib. By comparison with the performance of CDs, DAN, and their binary matrix, DAN-CDs were favored because of their lower matrix background interference and good detection sensitivity. In addition, the DAN-CDs matrix displayed good salt tolerance and was further applied for plasma detection and qualitative detection of endogenous FAs in a plasma sample. Furthermore, the covalent amide bonds in the DAN-CDs matrix reduced signal interference from the matrix. These results demonstrated that DAN-CDs are a novel negative ion mode matrix for the analysis of small molecules in bio-samples by MALDI-MS.
研究领域:
分析化学
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生物医学
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产品关联
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2025
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IF 11.3
Zufeng Qiu,Kexin Yang,Zijian Huang,Hongsheng Zhao,Zhiwei Lin,Qin Kuang,Zhaoxiong Xie
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has emerged as a superior technique for detecting small molecules, owing to the strategic utilization of inorganic nanomaterial matrices. Despite the impressive capabilities of various novel matrices, the underlying interaction mechanisms between inorganic matrices and analytes remain largely unexplored. In this study, we synthesized Co 3 O 4 nanocubes, Co(OH) 2 nanosheets, Co 3 O 4 /Co(OH) 2 heterojunctions, and Co 3 O 4 +Co(OH) 2 composites via a facile one-pot method. Amino acids were selected as model analytes for performance evaluation. Notably, the Co 3 O 4 /Co(OH) 2 heterojunctions significantly enhanced signal intensity and lowered detection limits to the parts-per-billion (ppb) level, outperforming Co 3 O 4 nanocubes, Co(OH) 2 nanosheets, and Co 3 O 4 +Co(OH) 2 composites. The detection results for environmental pollutants, especially in solutions containing real samples, highlight the outstanding performance of the heterojunction material as a matrix. Further characterization indicates that the formation of the heterojunction enhances nanoparticle dispersion and promotes the separation of photogenerated electron-hole pairs. Consequently, more photogenerated charge carriers can be transferred to the target analytes, facilitating their charging ability and ultimately enhancing signal intensity in MALDI-TOF MS. These results clearly demonstrate that the enhanced photocatalytic performance directly drives the improvement of MALDI-TOF MS performance, excluding interference from other factors. Thus, this study successfully combines photocatalytic mechanisms with MALDI-TOF MS mechanisms, providing new insights into the enhancement of MALDI-TOF MS performance. Additionally, it offers a new detection method for environmental pollutants.
研究领域:
分析化学
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环境科学
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材料科学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2016
·Vol. 6
·期 34
·28165-28170
·
IF 3.289
Xiang Shen,Bing Yan
A zinc-based anionic metal–organic framework, [HDMA]2[Zn2(BDC)3(DMA)]·6DMF (HDMA+: dimethylammonium, BDC2−: 1,4-benzenedicarboxilate, DMA: dimethylamine and DMF: N,N′-dimethylformamide) has been solvothermally synthesized. And its cations, HDMA+, are exchanged by various lanthanides to form the hybrid systems via a post-synthetic process. These lanthanide(III)-loaded materials have shown different luminescent behaviors, indicating that this kind of anionic MOF could effectively sensitive lanthanides and be used as a potential luminescent probe towards different lanthanide ions. Besides, this system exhibits selective adsorption ability to cationic dyes, such as Rhodamine B, Basic Red 2 and Methylene Blue. RhB@1 has a fastest selection and realizes the probing of various organic solvent molecules as well as volatile organic benzenes (VOBs), especially for sensing acetone and aniline.
研究领域:
材料科学
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化学
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分析化学
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产品关联
DOI
高影响因子
ANALYST
·
2020
·Vol. 145
·期 8
·3125-3130
·
IF 3.978
Dan Ouyang,Kailong Luo,Wende Ma,Jie Wu,Jing Li,Yanting He,Zongwei Cai,Zian Lin
A spherical vinyl-functionalized covalent-organic framework (COF-V) was prepared at room temperature by a facile method and applied as a novel substrate for surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS). Compared with conventional organic matrices, the spherical COF-V with high crystallinity and good monodispersity exhibited high sensitivity, no matrix background interference, wide-range applicability, high salt tolerance and reproducibility in the characterization of small molecules. Considering these advantages, the applicability of the spherical COF-V-based SELDI-MS method was successfully demonstrated by determining trace amounts of glucose in diabetic urine, which would be a promising candidate for clinical diagnosis of diabetes. In addition, the morphological effect and the desorption/ionization mechanism of the COF-V were investigated in detail and the results indicated that the spherical COF-V substrate could greatly enhance the LDI process compared with the bulk COF-V. This work not only extends the application of COFs in MS, but also offers a promising alternative for small molecule identification and clinical diagnosis of diabetes.
研究领域:
分析化学
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医学诊断
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Leina Dou,Tong Bu,Wentao Zhang,Bingxin Zhao,Qingfeng Yang,Lunjie Huang,Sihang Li,Chengyuan Yang,Jianlong Wang,Daohong Zhang
The nanomaterials based lateral flow immunoassays (LFIAs) have been widely used for on-site detection of small molecules contaminants. Nevertheless, their practical applications are often constrained by the complicated materials synthesis and surface modification process of nanomaterials. Herein, inspired by chemical-staining, a crystal violet (CV) staining based LFIAs was innovatively developed for the first time to analyze small molecules contaminant with significantly simplified behaviour and surpassing repeatability. This nanomaterials-free technique overcomes the intrinsic limitations of nanomaterials, owing to the superior protein dye property of CV. To demonstrate the feasibility of the unique strategy, furazolidone (FZD) was used as a model analyte, results showed detection limits of as low as 7 and 1.53 ng mL −1 by visual observation and quantitative analysis, respectively. Finally, to validate its applicability in actual conditions, the platform is well applied in three kinds of food samples (shrimp, fish and pork). Furthermore, as the detection principle is based on the molecular recognition between antigen and antibody, our method may find general applications by staining other antibodies against other target analytes.
研究领域:
分析化学
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食品安全
·
生物医学
✓ 已验证
DOI
高影响因子
OPTICS EXPRESS
·
2022
·Vol. 30
·期 15
·26136-26148
·
IF 3.833
Haoyuan Cai,Haoyuan Cai,Haoyuan Cai,Haoyuan Cai,Mengwei Wang,Mengwei Wang,Mengwei Wang,Jing Liu,Jing Liu,Xiaoping Wang,Xiaoping Wang,Xiaoping Wang,Xiaoping Wang
A high-sensitivity surface plasmon resonance (SPR) sensor based on the coupling of Au grating and Au film is investigated through simulations and experiments. The SPR sensor is designed by using a hybrid method composed of genetic algorithm (GA) and rigorous coupled wave analysis (RCWA). The numerical results indicate the sensor has an angular sensitivity of 397.3°/RIU (refractive index unit), which is approximately 2.81 times higher than the conventional Au-based sensor and it is verified by experiments. Theoretical analysis, by finite-difference time-domain (FDTD) method, demonstrates the co-coupling between surface plasmon polaritons (SPPs) propagating on the surface of Au film and localized surface plasmons (LSPs) in the Au grating nanostructure, improving the sensitivity of the SPR sensor. According to the optimized structural parameters, the proposed sensor is fabricated using e-beam lithography and magnetron sputtering. In addition, the proposed sensor is very sensitive to the detection of small molecules. The limit of detection (LOD) for okadaic acid (OA) is 0.72 ng/mL based on an indirect competitive inhibition method, which is approximately 38 times lower than the conventional Au sensor. Such a high-sensitivity SPR biosensor has potential in the applications of immunoassays and clinical diagnosis.
研究领域:
生物传感器
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光学传感
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医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）