Micromachines
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2018
·Vol. 9
·期 9
·470
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IF 2.222
Zhigang Gao,Zongzheng Chen,Jiu Deng,Xiaorui Li,Yueyang Qu,Lingling Xu,Yong Luo,Yao Lu,Tingjiao Liu,Weijie Zhao,Bingcheng Lin
Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker used in clinical applications. The primarily clinical method for measuring CEA is based on chemiluminescence in serum during enzyme-linked immunosorbent assays (ELISA) in 96-well plates. However, this multi-step process requires large and expensive instruments, and takes a long time. In this study, a high-throughput centrifugal microfluidic device was developed for detecting CEA in serum without the need for cumbersome washing steps normally used in immunoreactions. This centrifugal microdevice contains 14 identical pencil-like units, and the CEA molecules are separated from the bulk serum for subsequent immunofluorescence detection using density gradient centrifugation in each unit simultaneously. To determine the optimal conditions for CEA detection in serum, the effects of the density of the medium, rotation speed, and spin duration were investigated. The measured values from 34 clinical serum samples using this high-throughput centrifugal microfluidic device showed good agreement with the known values (average relative error = 9.22%). These results indicate that the high-throughput centrifugal microfluidic device could provide an alternative approach for replacing the classical method for CEA detection in clinical serum samples.Keywords:centrifugal microfluidic device;CEA detection;density medium;fluorescent chemiluminescence
研究领域:
生物医学工程
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临床检验学
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PubMed
高影响因子
MICROCHIMICA ACTA
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2024
·Vol. 191
·期 5
·1-12
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IF 5.3
Ouyang Ruizhuo,Feng Meina,Liu Jinyao,Wang Caihong,Wang Zhongmin,Hu Xin,Miao Yuqing,Zhou Shuang
Rapid and sensitive detection of carcinoembryonic antigen (CEA) is of great significance for cancer patients. Here, molybdenum (Mo) was doped into bismuth oxide (Bi 2 O 3 ) by one-pot hydrothermal method forming porous tremella Bi 2 MoO 6 nanocomposites with a larger specific surface area than the spherical structure. Then, a new kind of hydrangea-like TiO 2 /Bi 2 MoO 6 porous nanoflowers (NFs) was prepared by doping titanium into Bi 2 MoO 6 , where titanium dioxide (TiO 2 ) grew in situ on the surface of Bi 2 MoO 6 nanoparticles (NPs). The hydrangea-like structure provides larger specific surface area, higher electron transfer ability and biocompatibility as well as more active sites conducive to the attachment of anti-carcinoembryonic antigen (anti-CEA) to TiO 2 /Bi 2 MoO 6 NFs. A novel label-free electrochemical immunosensor was then constructed for the quantitative detection of CEA using TiO 2 /Bi 2 MoO 6 NFs as sensing platform, showing a good linear relationship with CEA in the concentration range 1.0 pg/mL ~ 1.0 mg/mL and a detection limit of 0.125 pg/mL (S/N = 3). The results achieved with the designed immunosensor are comparable with many existing immunosensors used for the detection of CEA in real samples. Graphical abstract
研究领域:
生物医学工程
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分析化学
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材料科学
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PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2024
·
IF 4.9
Yan Song,Weiyang Gao,Liang Sun,Junda Bai,Yi Zhang,Jingnan Zhu,Hua Xing,Chongyang Liang
The large decline in breast cancer mortality has been driven by rapid development and continuous progress in diagnostic techniques. However, it remains difficult to diagnose malignant lesions in distal branching ducts using mainstream techniques such as immunofluorescence ultrasound, molybdenum target, and ductoscopy. Combined with existing reports, we found that CEA level by ELISA in 13 patient 's nipple aspirate fluids (NAF) may be positively correlated with the malignancy of breast lesions. Here, considering the low content of CEA in NAF and the need for automated techniques for batch clinical testing, a magnetic induced mixing surface-enhanced Raman spectroscopy technique (SERS) was used to quantitatively analysis CEA concentration in NAF. In the appearance of CEA, an antibody-conjujated silver nano-probe (AgNPs-Ab1/4-ABP) can be linked onto the surface of another antibody-conjujated magnetic-probe. This immune sandwich-like structure enables more AgNPs-Ab1/4-ABP to remain in situ in the magnetic field. The magnetic spontaneous collection effect brings second SERS signal amplification at 1140 cm −1 approximately. After testing 10 clinical samples, the signal of Magnetic-Field Amplified SERS was not affected by the complex components in NAF, and a good linear range of 0.5–20 ng mL −1 could be achieved. This method might potentially be useful in the differential diagnoses of benign lesions with breast cancer and clinical follow-up of non-surgical intervention nipple discharge patients.
研究领域:
医学
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生物化学
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肿瘤学
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高影响因子
TALANTA
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2020
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IF 5.339
Wenjun Li,Yue Yang,Chaoyun Ma,Yiju Song,Xiuwen Qiao,Chenglin Hong
Traditional sandwich-type electrochemical immunosensors can only detect single tumor markers because signal interference occurs when detecting multiple tumor markers. In this work, an electrical signal difference strategy was proposed for the accurate detection of multiple tumor markers. We labeled PdAgCeO 2 mesoporous nanospheres with a carcinoembryonic antigen (CEA) secondary antibody and MnO 2 nanosheets labeled with an alpha-fetoprotein (AFP) secondary antibody. The two electrical signal tags were mixed and incubated on a prepared immunosensor to catalyze H 2 O 2 and generate an electrical signal I 1 (i-t ampere curve). When 2.5 mM ascorbic acid solution (AA) was added to 20 mL of PBS solution at pH = 6.5 for 180 s, an electrical signal I 2 was generated. I 2 was the current response of the CEA antigen concentration, and the electrical signal difference ΔI = I 1 – I 2 was the current response of the AFP antigen. Thus, the immunosensor accurately detected the AFP and CEA tumor markers. This method was called the electrical signal difference strategy. The proposed single-use immunosensor detected CEA antigens in a range of 0.001 ng/mL-40 ng/mL, and the detection limit was 0.5 pg/mL; the detection range of the AFP antigen was 0.005 ng/mL-100 ng/mL, and the detection limit was 1 pg/mL. Therefore, this study provides new ideas and strategies for accurate clinical detection of multiple tumor markers.
研究领域:
生物医学工程
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临床诊断
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高影响因子
BIOSENSORS & BIOELECTRONICS
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2016
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IF 7.476
Yueshuang Xu,Xiaoping Zhang,Chengxin Luan,Huan Wang,Baoan Chen,Yuanjin Zhao
Barcodes-based suspension array have for demonstrated values in multiplex assay of tumor markers. Photonic barcodes which are encoded by their characteristic reflection peaks are the important supports for suspension array due to their stable code, low fluorescent background and high surface-volume ratio. Attempts to develop this technology tend to improve the function of the photonic barcodes. Here, we present a new type of hybrid hydrogel photonic barcodes for efficient multiplex assays. This photonic barcodes are hybrid inverse opal hydrogel composed of poly(ethylene glycol) diacrylate (PEG-DA) and agarose . The polymerized PEG-DA hydrogel could guarantee the stabilities of the inverse opal structure and its resultant code, while the agarose could offer active chemical groups for the probe immobilization and homogeneous water surrounding for the bioassay. In addition, the interconnected pores inverse opal structure could provide channels for biomolecules diffusing and reaction into the voids of barcodes. These features imparted the hybrid hydrogel photonic barcodes with limits of detection (LOD) of 0.78 ng/mL for carcinoembryonic antigen (CEA) and 0.21 ng/mL for α-fetoprotein (AFP), respectively. It was also demonstrated that the proposed barcodes showed acceptable accuracy and detection reproducibility, and the results were in acceptable agreement with those from common clinic method for the detections of practical clinical samples. Thus, our technique provides a new platform for simultaneous multiplex immunoassay .
研究领域:
生物医学工程
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分析化学
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分子诊断
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PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
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2022
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IF 9.224
Chaoyun Ma,Chulei Zhao,Chenglin Hong,Li Zhang,Siyu Chen,Yu Qi
The quantitative detection of carcinoembryonic antigen (CEA) indicators is a critical step in the early clinical diagnosis of cancer because CEA is closely related to the development of cancer. However, the most commonly used methods for CEA detection mainly involve comparing or measuring the color depth of colored substance solutions, which is not highly accurate, particularly when a second colored substance is present in the solution to be evaluated. Herein, we rationalized the design of a photothermal probe based on calcium carbonate (CaCO3) as a protective shell (Cu2O@CaCO3) for cuprous oxide (Cu2O) nanoparticles to prevent Cu2O oxidation and hyaluronic acid (HA) to confer material biocompatibility (Cu2O@CaCO3@HA). Cu2O can be specifically activated by hydrogen sulfide (H2S), transformed into Cu31S16 nanoparticles and display significant photothermal properties that can be visualized for bioanalysis by simply recording the temperature signal with a thermal imager. In addition, the presence of redox pairs can provide further electrochemically assisted validation of the temperature identification system. Given the portable, economical, and sensitive biosensing, we anticipate that future activatable nanoprobes may be used to assist in early cancer diagnosis and screening.
研究领域:
医学诊断
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纳米生物技术
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癌症研究
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高影响因子
ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Chengli Xie,Longcheng Gong,Tong Xu,Lianzhe Hu,Zhining Xia,Min Wang
To overcome the limitation of low catalytic activity in nanozyme labels for immunoassay, this study proposed a heterovalent Co-doping strategy to construct the bimetallic Zr/Co-UiO-66-NH2 nanozyme. Compared to the undoped UiO-66-NH2, the resulting nanozyme exhibited a 14-fold enhancement in phosphatase-like catalytic efficiency (kcat/Km). Mechanistic investigations revealed that the activity enhancement was not only dependent on the high specific surface area and increased defects introduced by heterovalent Co doping, but also was attributed to the electronic synergy between Zr and Co. Furthermore, a fluorescent immunoassay method utilizing highly efficient Zr/Co-UiO-66-NH2 as the nanozyme label was developed for the ultrasensitive detection of carcinoembryonic antigen (CEA). This method achieved a broad linear detection range spanning 6 orders of magnitude (1 × 10–12 g/mL to 1 × 10–6 g/mL) and a detection limit as low as 0.74 × 10–12 g/mL. The high recovery rates (95.89%–99.31%) in serum samples demonstrate great potential for the detection of CEA in complex biological matrices.
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Frontiers in Immunology
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2026
·
IF 7
Gaohua Li,Lingping Zhao,Jingzhi Shen,Haiyang Wang,Jinru He,Yiming Liu,Ruge Zang,Tiantian Cui,Quan Zeng,Junnian Zhou,Wen Yue,Yanan Wang,Jiafei Xi
BackgroundCarcinoembryonic antigen (CEA) is overexpressed in most colorectal cancers (CRC) and serves as a promising immunotherapeutic target. However, current immune cell therapies against CRC show limited clinical efficacy, and the lack of renewable, standardized cell sources hampers broader application. The present study aimed to establish a scalable source of CEA-targeted natural killer (NK) cells from engineered human embryonic stem cells (hESCs).MethodshESCs were genetically engineered to express a CEA‑specific chimeric antigen receptor (CAR). The modified hESCs were subsequently differentiated into NK cells, yielding a homogeneous population of CAR hESC-NK cells. In vitro cytotoxicity against CEA-high CRC cell lines was evaluated using LDH and IFN-γ release assays. For in vivo assessment, we established a xenograft mouse model bearing CEA-positive CRC tumors. Following adoptive transfer of CAR-hESC-NK cells, tumor growth was monitored by bioluminescence imaging, overall survival was recorded for Kaplan–Meier analysis, and the persistence of transferred cells in peripheral blood was examined by flow cytometric analysis at serial time points.ResultsIn vitro, CAR hESC‑NK cells demonstrated potent and specific cytotoxicity against CEA-high CRC cell lines, along with significantly enhanced cytokine secretion compared to unmodified NK cells. In the xenograft model, adoptive transfer of CAR hESC‑NK cells resulted in marked tumor growth inhibition and prolonged survival, with no observable off‑target toxicity. Importantly, the CAR CEA‑ESC line maintained stable transgene expression and could serve as a renewable seed cell source.ConclusionWe have established a scalable platform for producing CEA‑targeted NK cells from engineered hESCs, providing an off‑the‑shelf, homogeneous cell product with robust antitumor activity. This strategy provides effective and specific immunotherapy against CEA-positive colorectal cancer and holds potential for other CEA-expressing malignancies.
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ANALYTICAL CHEMISTRY
·
2017
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IF 6.32
Zhenli Qiu,Jian Shu,Dianping Tang
Titanium dioxide (TiO2; as a potential photosensitizer) has good photocurrent performance and chemical stability but often exhibits low utilization efficiency under ultraviolet (UV) region excitation. Herein, we devised a near-infrared light-to-UV light-mediated photoelectrochemical (PEC) aptasensing platform for the sensitive detection of carcinoembryonic antigen (CEA) based on core–shell NaYF4:Yb,Tm@TiO2 upconversion microrods by coupling with target-triggered rolling circle amplification (RCA). The upconversion microrods synthesized through the hydrothermal reaction could act as a photosensing platform to convert the near-infrared (near-IR) excitation into UV emission for generation of photoinduced electrons. The target analyte was determined on a functional magnetic bead by using the corresponding aptamers with a sandwich-type assay format. Upon target CEA introduction, a complex was first formed between capture aptamer-1-conjugated magnetic bead (Apt1-MB) and aptamer-2-primer DNA (Apt2-pDNA). Thereafter, the carried primer DNA by the aptamer-2 paired with linear padlock DNA to trigger the RCA reaction. The guanine (G)-rich product by RCA reaction was cleaved by exonuclease I and exonuclease III (Exos I/III), thereby resulting in the formation of numerous individual guanine bases to enhance the photocurrent of core–shell NaYF4:Yb,Tm@TiO2 upconversion microrods under near-IR illumination (980 nm). Under optimal conditions, the near-IR light-mediated PEC aptasensing system could exhibit good photoelectrochemical response toward target CEA and allowed for the detection of target CEA as low as 3.6 pg mL–1. High reproducibility and good accuracy were achieved for analysis of human serum specimens. Importantly, the near-IR-activated PEC aptasensing scheme provides a promising platform for ultrasensitive detection of other biomolecules.
研究领域:
生物医学工程
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分析化学
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癌症诊断
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高影响因子
PROCESS BIOCHEMISTRY
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2019
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IF 2.883
Bing Zhang,Yejing Jia,Jing Wang,Honghong Chang,Zhihuan Zhao,Yan Cheng
Under the limitations of advanced instruments and professional operations, straightforward readouts play an increasingly vital role in immunoassays. Herein, a Ag 2 CO 3 @Ag nanocomposite-mediated colorimetric and photothermal immunoassay was developed to detect carcinoembryonic antigen (CEA). The Ag 2 CO 3 @Ag nanocomposites could oxidize 3,3’,5,5’-tetramethylbenzidine to form blue oxidation products (TMB ox ) due to the acidic dissolution of Ag 2 CO 3 under acidic conditions. TMB ox presented a strong photothermal effect driven by a near-infrared (NIR) laser. Therefore, TMB ox could act as a photothermal probe to convert immunoassay signals into thermal signals. The Ag 2 CO 3 @Ag nanocomposite was characterized by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and X-ray powder diffraction (XRD). Then, a sandwich-type immunoassay was built on the surface of a magnetic bead, and CEA was quantified using a common thermometer based on the photothermal effect. Under optimal conditions, the temperature increased with increase of CEA concentrations in the range of 0.1 ng/mL–5 ng/mL. More importantly, this system exhibited high selectivity, good repeatability and outstanding stability.
研究领域:
生物化学
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医学诊断
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纳米技术
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高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2023
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IF 3.4
Xue Su,Qiannan You,Linlin Zhuang,Zhimin Chang,Mingfeng Ge,Li Yang,Wen-Fei Dong
Circulating tumor cells (CTCs) are important prognostic markers for cancer diagnosis and metastasis, and their detection is an important means to detect cancer metastasis. Herein, we construct a novel bifunctional electrochemical biosensor based on the PB-MXene composite films. A simple electrostatic self-assembly approach was employed to prepare a film composed of PB nanocubes on the MXene substrates. Given that the PB is an artificial peroxidase for H 2 O 2 sensing, the PB-MXene films can realize the real-time monitoring of H 2 O 2 secretion from living CTCs. Besides, the anti-CEA attached biosensors can be utilized to quantify the corresponding CTCs. The synergic effects of the MXene with a large specific area and PB with enzyme-free catalysis for H 2 O 2 resulted in PB-MXene films exhibiting high electrocatalytic and low cytotoxicity for both H 2 O 2 sensing and living CTCs capturing. As a result, the biosensor shows a low detection limit of 0.57 μM towards H 2 O 2 with a wide linear range (1 μM to 500 μM), as well as an excellent sensing performance for CTCs (an extremely low detection limit of 9 cells/mL in a wide linear range of 1.3 ×10 1 to 1.3 ×10 6 cells/mL). Moreover, the prepared biosensor showed satisfactory stability and anti-interference ability for potential applications in clinical cancer diagnosis and tumor metastasis.
研究领域:
生物医学工程
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癌症诊断
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高影响因子
ANALYST
·
2023
·Vol. 148
·期 14
·3295-3305
·
IF 4.2
Yong Huang,Zhengqing Liu,Xiaogang Qin,Jia Liu,Yan Yang,Wei Wei
Highly sensitive protein biomarker detection is critical for the diagnosis of gastric cancer (GC), however the accurate and sensitive detection of low-abundance proteins in early-stage GC is still a challenge. Herein, a surface-enhanced Raman scattering frequency shift assay was performed on a developed microfluidic chip for the detection of GC protein biomarkers carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF). The chip is made up of three groups of parallel channels and each parallel channel consists of two reaction regions, enabling the simultaneous analysis of multiple biomarkers in multiple samples. The presence of CEA and VEGF in the sample can be captured by the 4-mercaptobenzoic acid (4-MBA)-conjugated antibody functionalized gold nano-sheet (GNS-) substrate, resulting in the Raman frequency shift. As a result, a typical Raman frequency shift of 4-MBA presented a linear relationship with the concentration of CEA and VEGF. The limit of detection (LOD) of the proposed SERS microfluidic chip reaches as low as 0.38 pg mL−1 for CEA and 0.82 pg mL−1 for VEGF. During the detection process, only one step of sample addition is involved, which eliminates the multiple reaction step-induced nonspecific adsorption and significantly increases the convenience and specificity. In addition, serum samples from GC patients and healthy subjects were tested and the results were in good agreement with the current gold-standard method ELISA, suggesting the potential application of the SERS microfluidic chip in clinical settings for early diagnosis and prognosis of GC.
研究领域:
医学
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分析化学
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纳米技术
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PubMed
高影响因子
危险品化学品经营许可证（带存储）