2D Film-Like Magnetic SERS Tag with Enhanced Capture and Detection Abilities for Immunochromatographic Diagnosis of Multiple Bacteria.

Here, a multiplex surface-enhanced Raman scattering (SERS)-immunochromatography (ICA) platform is presented using a graphene oxide (GO)-based film-like magnetic tag (GFe-DAu-D/M) that effectively captures and detects multiple bacteria in complex specimens. The 2D GFe-DAu-D/M tag with universal bacterial capture ability is fabricated through the layer-by-layer assembly of one layer of small Fe3O4 nanoparticles (NPs) and two layers of 30 nm AuNPs with a 0.5 nm built-in nanogap on monolayer GO nanosheets followed by co-modification with 4-mercaptophenylboronic acid (MPBA) and 5,5'-dithiobis-(2-nitrobenzoic acid).The GFe-DAu-D/M enabled the rapid enrichment of multiple bacteria by MPBA and quantitative analysis of target bacteria on test lines by specific antibodies, thus achieving multiple signal amplification of magnetic enrichment effect and multilayer dense hotspots and eliminating matrix interference in real-world applications. The developed technology can directly and simultaneously diagnose three major pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhimurium) with detection limits down to the level of 10 cells mL-1. The good performance of the proposed method in the detection of real urinary tract infection specimens is also demonstrated, suggesting the great potential of the GFe-DAu-D/M-ICA platform for the highly sensitive monitoring of bacterial infections or contamination.

A nanogap-enhanced SERS nanotag-based lateral flow assay for ultrasensitive and simultaneous monitoring of SARS-CoV-2 S and NP antigens.

A lateral flow assay (LFA) strip based on dual 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB)-encoded satellite Fe3O4@Au (Mag@Au) SERS tags with nanogap is reported for  ultrasensitive and simultaneous diagnosis of two SARS-CoV-2 functional proteins. Composed of Fe3O4 core, satellite gold shell with nanogaps, and double-layer DTNB, the Mag@Au nanoparticles with an average size of 238 nm were designed as multifunctional tags to efficiently enrich the target SARS-CoV-2 protein from complex samples, significantly enhancing the SERS signal of the LFA strip and provide quantitative SERS detection of analyte on test lines. The developed dual DTNB-encoded satellite Mag@Au-based LFA allowed simultaneous quantification of spike (S) protein and nucleocapsid (NP) protein with detection limits of 23 pg mL-1 and 2 pg mL-1, respectively, lower than commercial ELISA kits and reported SERS-LFA detection system-based Au NPs and Fe3O4@3 nm Au MNPs. This magnetic SERS-LFA also showed high performance of multi-variant strain detection and further distinguished clinical samples of Omicron variant infection, demonstrating the potential of in situ detection of respiratory virus diseases.

Fluorescence-enhanced dual signal lateral flow immunoassay for flexible and ultrasensitive detection of monkeypox virus.

The outbreak of the monkeypox virus (MPXV) worldwide in 2022 highlights the need for a rapid and low-cost MPXV detection tool for effectively monitoring and controlling monkeypox disease. In this study, we developed a flexible lateral flow immunoassay (LFIA) with strong colorimetric and enhanced fluorescence dual-signal output for the rapid, on-site, and highly sensitive detection of the MPXV antigen in different scenarios. A multilayered SiO2-Au core dual-quantum dot (QD) shell nanocomposite (named SiO2-Au/DQD), which consists of a large SiO2 core (~ 200 nm), one layer of density-controlled gold nanoparticles (AuNPs, 20 nm), and thousands of small QDs, was fabricated instead of a traditional colorimetric nanotag (i.e., AuNPs) and a fluorescent nanotag (QD nanobead) to simultaneously provide good stability, strong colorimetric ability and superior fluorescence intensity. With the dual-signal output LFIA, we achieved the specific screening of the MPXV antigen (A29L) in 15 min, with detection limits of 0.5 and 0.0021 ng/mL for the colorimetric and fluorometric modes, respectively. Moreover, the colorimetric mode of SiO2-Au/DQD-LFIA exhibits the same sensitivity as the traditional AuNP- LFIA, whereas the overall sensitivity of this method on the basis of the fluorescent signal can achieve 238- and 3.3-fold improvements in sensitivity for MPXV compared with the AuNP-based LFIA and ELISA methods, respectively, indicating the powerful performance and good versatility of the dual-signal method in the point-of-care testing of the MPXV.

Simultaneously ultrasensitive and quantitative detection of influenza A virus, SARS-CoV-2, and respiratory syncytial virus via multichannel magnetic SERS-based lateral flow immunoassay.

Respiratory viruses usually induced similar clinical symptoms at early infection. Herein, we presented a multichannel surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-based LFA) using high-performance magnetic SERS tags for the simultaneous ultrasensitive detection of respiratory viruses, namely influenza A virus (H1N1), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) in biological samples. As-prepared magnetic SERS tags can directly enrich and capture target viruses without pretreatment of samples, avoiding the interference of impurities in the samples as well as improving the sensitivity. With the capture-detection method, the detection limits of the proposed assay reached 85 copies mL-1, 8 pg mL-1, and 8 pg mL-1 for H1N1, SARS-CoV-2 and RSV, respectively. Moreover, the detection properties of the proposed method for target viruses in throat swab samples were verified, suggesting its remarkable potential for the early and rapid differential diagnosis of respiratory viruses.

Molecular Toxicology and Cancer Prevention.

Molecular toxicology is a field that investigates the interactions between chemical or biological molecules and organisms at the molecular level [...].

Rapid field determination of SARS-CoV-2 by a colorimetric and fluorescent dual-functional lateral flow immunoassay biosensor.

The rapid and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the early stage of virus infection can effectively prevent the spread of the virus and control the epidemic. Here, a colorimetric and fluorescent dual-functional lateral flow immunoassay (LFIA) biosensor was developed for the rapid and sensitive detection of spike 1 (S1) protein of SARS-CoV-2. A novel dual-functional immune label was fabricated by coating a single-layer shell formed by mixing 20 nm Au nanoparticles (Au NPs) and quantum dots (QDs) on SiO2 core to produce strong colorimetric and fluorescence signals and ensure good monodispersity and high stability. The colorimetric signal was used for visual detection and rapid screening of suspected SARS-CoV-2 infection on sites. The fluorescence signal was utilized for sensitive and quantitative detection of virus infection at the early stage. The detection limits of detecting S1 protein via colorimetric and fluorescence functions of the biosensor were 1 and 0.033 ng/mL, respectively. Furthermore, we evaluated the performance of the biosensor for analyzing real samples. The novel biosensor developed herein had good repeatability, specificity and accuracy, which showed great potential as a tool for rapidly detecting SARS-CoV-2.

Development of spike protein-based fluorescence lateral flow assay for the simultaneous detection of SARS-CoV-2 specific IgM and IgG.

The pandemic outbreak of the 2019 coronavirus disease (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still spreading rapidly and poses a great threat to human health. As such, developing rapid and accurate immunodiagnostic methods for the identification of infected persons is needed. Here, we proposed a simple but sensitive on-site testing method based on spike protein-conjugated quantum dot (QD) nanotag-integrated lateral flow immunoassay (LFA) to simultaneously detect SARS-CoV-2-specific IgM and IgG in human serum. Advanced silica-core@dual QD-shell nanocomposites (SiO2@DQD) with superior luminescence and stability were prepared to serve as fluorescent nanotags in the LFA strip and guarantee high sensitivity and reliability of the assay. The performance of the SiO2@DQD-strip was fully optimized and confirmed by using 10 positive serum samples from COVID-19 patients and 10 negative samples from patients with other respiratory diseases. The practical clinical value of the assay was further evaluated by testing 316 serum samples (114 positive and 202 negative samples). The overall detection sensitivity and specificity reached 97.37% (111/114) and 95.54% (193/202), respectively, indicating the huge potential of our proposed method for the rapid and accurate detection of SARS-CoV-2-infected persons and asymptomatic carriers.

Development of a SERS-based lateral flow immunoassay for rapid and ultra-sensitive detection of anti-SARS-CoV-2 IgM/IgG in clinical samples.

The accurate and rapid screening of serum antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the key to control the spread of 2019 coronavirus disease (COVID-19). In this study, we reported a surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-LFIA) for the simultaneous detection of anti-SARS-CoV-2 IgM/IgG with high sensitivity. Novel SERS tags labeled with dual layers of Raman dye were fabricated by coating a complete Ag shell on SiO2 core (SiO2@Ag) and exhibited excellent SERS signals, good monodispersity, and high stability. Anti-human IgM and IgG were immobilized onto the two test lines of the strip to capture the formed SiO2@Ag-spike (S) protein-anti-SARS-CoV-2 IgM/IgG immunocomplexes. The SERS signal intensities of the IgM and IgG test zones were easily recorded by a portable Raman instrument and used for the high-sensitivity analysis of target IgM and IgG. The limit of detection of SERS-LFIA was 800 times higher than that of standard Au nanoparticle-based LFIA for target IgM and IgG. The SERS-LFIA biosensor was tested on 19 positive serum samples from COVID-19 patients and 49 negative serum samples from healthy people to demonstrate the clinical feasibility of our proposed assay. The results revealed that the proposed method exhibited high accuracy and specificity for patients with SARS-CoV-2 infection.

Development of an ultrasensitive fluorescent immunochromatographic assay based on multilayer quantum dot nanobead for simultaneous detection of SARS-CoV-2 antigen and influenza A virus.

Rapid and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (FluA) antigens in the early stages of virus infection is the key to control the epidemic spread. Here, we developed a two-channel fluorescent immunochromatographic assay (ICA) for ultrasensitive and simultaneous qualification of the two viruses in biological samples. A high-performance quantum dot nanobead (QB) was fabricated by adsorption of multilayers of dense quantum dots (QDs) onto the SiO2 surface and used as the highly luminescent label of the ICA system to ensure the high-sensitivity and stability of the assay. The combination of monodispersed SiO2 core (∼180 nm) and numerous carboxylated QDs formed a hierarchical shell, which ensured that the QBs possessed excellent stability, superior fluorescence signal, and convenient surface functionalization. The developed ICA biosensor achieved simultaneous detection of SARS-CoV-2 and FluA in one test within 15 min, with detection limits reaching 5 pg/mL for SARS-CoV-2 antigen and 50 pfu/mL for FluA H1N1. Moreover, our method showed high accuracy and specificity in throat swab samples with two orders of magnitude improvement in sensitivity compared with traditional AuNP-based ICA method. Hence, the proposed method is a promising and convenient tool for detection of respiratory viruses.

Sensitive and Simultaneous Detection of SARS-CoV-2-Specific IgM/IgG Using Lateral Flow Immunoassay Based on Dual-Mode Quantum Dot Nanobeads.

A rapid and accurate method for detection of virus (SARS-CoV-2)-specific antibodies is important to contain the 2019 coronavirus disease (COVID-19) outbreak, which is still urgently needed. Here, we develop a colorimetric-fluorescent dual-mode lateral flow immunoassay (LFIA) biosensor for rapid, sensitive, and simultaneous detection of SARS-CoV-2-specific IgM and IgG in human serum using spike (S) protein-conjugated SiO2@Au@QD nanobeads (NBs) as labels. The assay only needs 1 µL of the serum sample, can be completed within 15 min, and is 100 times more sensitive than the colloidal gold-based LFIA. Two detection modes of our biosensor are available: the colorimetric mode for rapid screening of the patients with suspected SARS-CoV-2 infection without any special instrument and the fluorescent mode for sensitive and quantitative analyses to determine the concentrations of specific IgM/IgG in human serum and detect the infection early and precisely. We validated the proposed method using 16 positive serum samples from patients with COVID-19 and 41 negative samples from patients with other viral respiratory infections. The results demonstrated that combined detection of virus-specific IgM and IgG via SiO2@Au@QD LFIA can identify 100% of patients with SARS-CoV-2 infection with 100% specificity.

Rapid Enrichment and Ultrasensitive Detection of Influenza A Virus in Human Specimen using Magnetic Quantum Dot Nanobeads Based Test Strips.

Influenza A virus (IAV) possesses a high infectivity and pathogenicity, and can lead to severe respiratory infection with similar symptoms caused by some other common respiratory viruses. Lateral flow assay (LFA) has been widely deployed in remote settings as a rapid and reliable approach for point-of-care detection of infectious pathogens. However, it still remains challenging to detect IAV virions using LFA from clinical samples such as nasopharyngeal or throat swabs, because their various components and high viscosity can decrease flow velocity and lead to the nonspecific adsorption of nanoparticle labels on the sensing membrane. Herein, we demonstrated a magnetic quantum dot nanobeads (MQBs) based LFA for magnetic enrichment and fluorescent detection of IAV virions in clinical specimens. In this study, MQBs were synthesized and then conjugated with IAV-specific antibody to efficiently enrich IAV virions from complex biological matrix, but also serve as highly bright fluorescent probes in lateral flow strips. This assay can achieve quantitative detection of IAV virions with a low limit of detection down to 22 pfu mL-1 within 35 minutes, and show good specificity between influenza B virus and two adenovirus strains. Furthermore, the presented platform was able to directly detect IAV virions spiked in nasopharyngeal swab dilution, indicating its stability and feasibility in clinical applications. Thus, this point-of-care detection platform holds great promise as a broadly applicable approach for the rapid diagnosis of influenza A.

Quantitative and simultaneous detection of two inflammation biomarkers via a fluorescent lateral flow immunoassay using dual-color SiO2@QD nanotags.

An on-site detection strategy is reported based on dual-color SiO2@quantum dot (QD)-integrated lateral flow immunoassay (LFA) strip to realize the quantitative and simultaneous detection of C-reactive protein (CRP) and procalcitonin (PCT) in serum. The dual-color SiO2@QD nanotags with monodispersity and excellent luminescence were synthesized using polyethyleneimine-mediated electrostatic adsorption of dense red CdSe/ZnS-COOH (excitation/emission 365/625 nm) or green CdSe/ZnS-COOH (excitation/emission 365/525 nm) QDs on the surface of 180 nm SiO2 spheres and were conjugated with anti-PCT and anti-CRP monoclonal antibodies, as stable and fluorescent-enhanced QD nanotags in the LFA system. The use of SiO2@QDs with two different fluorescent signals caused the sensitivity and specificity of the multiplex LFA system. As a result, the proposed assay provided a wide logarithmic determination range with a CRP quantitative range of 0.5-103 ng/mL and PCT quantitative range of 0.05-103 ng/mL. The limits of detection (LODs) of CRP and PCT reached 0.5 and 0.05 ng/mL, respectively. The SiO2@QD-based LFA showed great potential as rapid detection tool for the simultaneous monitoring of CRP and PCT in serum sample.

Rapid identification and antibiotic susceptibility test of pathogens in blood based on magnetic separation and surface-enhanced Raman scattering.

An effective surface-enhanced Raman scattering (SERS) method is presented for the rapid identification and drug sensitivity analysis of pathogens in blood. In a first step, polyethyleneimine-modified magnetic microspheres (Fe3O4@PEI) were used to enrich bacteria from blood samples. Next, the Fe3O4@PEI@bacteria complex was cultured on both ordinary and drug-sensitive plates. Lastly, the SERS spectra of single colonies were acquired in order to identify different pathogens and their resistant strains by comparison with established standardized bacterial SERS spectras and orthogonal partial least squares discriminant analysis (OPLS-DA) method. Staphylococcus aureus, Acinetobacter baumannii, Pseudomonas aeruginosa and their resistant strains were used to evaluate the performance of the SERS method. The results demonstrate that the method can accurately detect and identify all the tested sensitive and drug-resistant strains of bacteria, including 77 clinical blood infection samples. The method provides a way for rapid identification and susceptibility test of pathogens, and has great potential to replace currently used time-consuming methods. Graphical abstract Schematic presentation of a method for the rapid identification and drug sensitivity analysis of pathogens in blood. It is based on a combination of magnetic separation, SERS fingerprint analysis and orthogonal partial least squares discriminant analysis (OPLS-DA).

Dual-Selective and Dual-Enhanced SERS Nanoprobes Strategy for Circulating Hepatocellular Carcinoma Cells Detection.

The detection of hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) from a blood sample can be a very powerful noninvasive approach for the early detection and therapy of liver cancer. However, the extreme rarity of tumor cells in blood containing billions of other cells makes the capture and identification of CTCs with sufficient sensitivity and specificity a real challenge. Here, a magnetically assisted surface-enhanced Raman scattering (SERS) biosensor for HCC CTC detection is reported for the first time. The biosensor consists of two basic elements: anti-ASGPR antibody-Fe3 O4 @Ag magnetic nanoparticles and anti-GPC3 antibody-Au@Ag@DTNB nanorods. According to the dual-selectivity of the anti-ASGPR and anti-GPC3 antibodies and the dual-enhancement SERS signal of the MNPs silver shell and the Au@Ag NRs SERS tags, a limit of detection of 1 cell mL-1 for HCC CTC in human peripheral blood samples with a linear relationship from 1 to 100 cells mL-1 can be obtained. The system shows good performance in real serum, which suggests it may be a promising tool for HCC clinical diagnosis.

Fast and non-invasive serum detection technology based on surface-enhanced Raman spectroscopy and multivariate statistical analysis for liver disease.

This study explored a rapid and nondestructive liver disease detection technique based on surface-enhanced Raman spectroscopy (SERS) to realize the early diagnosis, prevention, and treatment of liver disease. SERS signals of serum were obtained from 304 normal individuals, 333 patients with hepatopathy, and 99 patients with esophageal cancer. The Raman spectra of different diseases were compared and diagnostic models of liver disease were established using orthogonal partial least squares discriminant analysis (OPLS-DA). The classification efficiencies of the different models were comprehensively evaluated through the receiver operating characteristic (ROC) curve and ten-fold cross validation. Area under the ROC curve is of greater than 0.97, indicating excellent classification of the groups. The accuracy rate of the test set reached 95.33%, and the lowest was 81.76% using the ten-fold cross validation. Thus, OPLS-DA combined with serum SERS is a rapid and non-invasive technique for the diagnosis of liver disease.

The effects of life review interventions on spiritual well-being, psychological distress, and quality of life in patients with terminal or advanced cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Life review interventions have been used to alleviate psycho-spiritual distress in people near the end of life. However, their effectiveness remains inconclusive. AIM: To evaluate the effects of therapeutic life review on spiritual well-being, psychological distress, and quality of life in patients with terminal or advanced cancer. DESIGN: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. DATA SOURCES: Five databases were searched from their respective inception through February 2017 for relevant randomized controlled trials. The effects of therapeutic life review were pooled across the trials. Standardized mean differences were calculated for the pooled effects. Heterogeneity was assessed using the I2 test. Study quality was assessed using the Cochrane criteria. RESULTS: Eight randomized controlled trials met the inclusion criteria. The pooled results suggested a desirable effect of therapeutic life review on the meaning of life domain of spiritual well-being (standardized mean difference = 0.33; 95% confidence interval, 0.12 to 0.53), general distress (standardized mean difference = -0.32; 95% confidence interval, -0.55 to -0.09), and overall quality of life (standardized mean difference = 0.35; 95% confidence interval, 0.15 to 0.56) when compared to usual care only. Of the three outcomes examined, only the pooled effect on overall quality of life remained statistically significant at follow-ups up to 3 months after the intervention (standardized mean difference = 0.82; 95% confidence interval, 0.47 to 1.18). CONCLUSIONS: Therapeutic life review is potentially beneficial for people near the end of life. However, the results should be interpreted with caution due to the limited number of randomized controlled trials and associated methodological weaknesses. Further rigorously designed randomized controlled trials are warranted.

The effect of different screw-rod design on the anti-rotational torque: a biomechanical comparison of three conventional screw-rod constructs.

BACKGROUND: Screw-rod constructs have been widely used to correct spinal deformities, but the effects of different screw-rod systems on anti-rotational torque have not been determined. This study aimed to analyze the biomechanical effect of different rod-screw constructs on anti-rotational torque. METHODS: Three conventional spinal screw-rod systems (Legacy, RF-F-10 and USSII) were used to test the anti-rotational torque in the material test machine. ANOVA was performed to evaluate the anti-rotational capacity of different pedicle screws-rod constructs. RESULTS: The anti-rotational torque of Legacy group, RF-F-10 group and USSII group were 12.3 ± 1.9 Nm, 6.8 ± 0.4 Nm, and 3.9 ± 0.8 Nm, with a P value lower than 0.05. This results indicated that the Legacy screws-rod construct could provide a highest anti-rotation capacity, which is 68% and 210% greater than RF-F-10 screw-rod construct and USSII screw-rod respectively. CONCLUSIONS: The anti-rotational torque may be mainly affected by screw cap and groove design. Our result showed the anti-rotational torque are: Legacy system > RF-F-10 system > USSII system, suggesting that appropriate rod-screw constructs selection in surgery may be vital for anti-rotational torque improvement and preventing derotation correction loss.

Social workers' involvement in advance care planning: a systematic narrative review.

BACKGROUND: Advance care planning is a process of discussion that enables competent adults to express their wishes about end-of-life care through periods of decisional incapacity. Although a number of studies have documented social workers' attitudes toward, knowledge about, and involvement in advance care planning, the information is fragmented. The purpose of this review was to provide a narrative synthesis of evidence on social workers' perspectives and experiences regarding implementation of advance care planning. METHODS: Six databases were searched for peer-reviewed research papers from their respective inception through December 2016. All of the resulting studies relevant to both advance care planning and social worker were examined. The findings of relevant studies were synthesized thematically. RESULTS: Thirty-one articles met the eligibility criteria. Six research themes were identified: social workers' attitudes toward advance care planning; social workers' knowledge, education and training regarding advance care planning; social workers' involvement in advance care planning; social workers' perceptions of their roles; ethical issues relevant to advance care planning; and the effect of social work intervention on advance care planning engagement. The findings suggest that there is a consensus among social workers that advance care planning is their duty and responsibility and that social workers play an important role in promoting and implementing advance care planning through an array of activities. CONCLUSIONS: This study provides useful knowledge for implementing advance care planning through illustrating social workers' perspectives and experiences. Further studies are warranted to understand the complexity inherent in social workers' involvement in advance care planning for different life-limiting illnesses or within different socio-cultural contexts.

A rapid SERS method for label-free bacteria detection using polyethylenimine-modified Au-coated magnetic microspheres and Au@Ag nanoparticles.

A rapid, sensitive, and label-free SERS detection method for bacteria pathogens is reported for the first time. The method, which is based on the combination of polyethylenimine (PEI)-modified Au-coated magnetic microspheres (Fe3O4@Au@PEI) and concentrated Au@Ag nanoparticles (NPs), was named the capture-enrichment-enhancement (CEE) three-step method. A novel Fe3O4@Au microsphere with monodispersity and strong magnetic responsiveness was synthesized as a magnetic SERS substrate and amino functionalized by PEI self-assembly. The negatively charged bacteria were quickly captured and enriched by the positively charged Fe3O4@Au@PEI microspheres, and the bacteria SERS signal was synergistically enhanced by using Fe3O4@Au@PEI microspheres and Au@Ag NPs in conjunction. The CEE three-step method proved useful in tap water and milk samples, and the total assay time required was only 10 min. Results further demonstrated that the CEE three-step method could be a common approach for detecting a wide range of bacteria, as verified by its detection of the Gram-positive bacterium E. coli and Gram-positive bacterium S. aureus at a detection limit of as low as 103 cells per mL. Therefore, our CEE three-step method offered the significant advantages of short assay time, simple operating procedure, and higher sensitivity than previously reported methods of SERS-based bacteria detection.

Non-invasive detection of hepatocellular carcinoma serum metabolic profile through surface-enhanced Raman spectroscopy.

The present study aims to identify distinctive Raman spectrum metabolic peaks to predict hepatocellular carcinoma (HCC). We performed a label-free, non-invasive surface-enhanced Raman spectroscopy (SERS) test on 230 serum samples including 47 HCC, 60 normal controls (NC), 68 breast cancer (BC) and 55 lung cancer (LC) by mixing Au@AgNRs with serum directly. Based on the observed SERS spectra, discriminative metabolites including tryptophan, phenylalanine, and etc. were found in HCC, when compared with BC, LC, and NC (P<0.05 in all). Common metabolites-proline, valine, adenine and thymine were found in HCC, BC and LC with compared to NC group (P<0.05). Importantly, Raman spectra of HCC serum biomarker AFP were firstly detected to analyze the HCC prominent peak. Orthogonal partial least squares discriminant analysis was adopted to assess the diagnostic accuracy; area under curve value of HCC is 0.991. This study provides new insights into the HCC metabolites detection through Raman spectroscopy.