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1.
Zhongguo Zhong Yao Za Zhi ; 47(22): 6183-6190, 2022 Nov.
Article in Chinese | MEDLINE | ID: mdl-36471943

ABSTRACT

Taking lipophagy as the breakthrough point, we explored the mechanism of Zexie Decoction(ZXD) in improving lipid metabolism in the hepatocyte model induced by palmitic acid(PA) and in the animal model induced by high-fat diet(HFD) on the basis of protein kinase B(Akt)/transcription factor EB(TFEB) signaling pathway. Co-localization was carried out for the microtubule-associated protein light chain 3(LC3) plasmid labeled with green fluorescent protein(GFP) and lipid droplets(LDs), and immunofluorescence co-localization for liver LC3 of HFD mice and perilipin 2(PLIN2). The results showed that ZXD up-regulated the expression of LC3, reduced lipid accumulation in hepatocytes, and increased the co-localization of LC3 and LDs, thereby activating lipo-phagy. Western blot results confirmed that ZXD increased autophagy-related protein LC3Ⅱ/LC3Ⅰ transformation ratio and lysosome-associated membrane protein 2(LAMP2) in vivo and in vitro and promoted the degradation of sequestosome-1(SQSTM1/p62)(P<0.05). The results above jointly explained that ZXD regulated lipophagy. Furthermore, ZXD activated TFEB expression(P<0.05) and reversed the PA-and HFD-induced decrease of TFEB nuclear localization in hepatocytes(P<0.05). Meanwhile, ZXD activated liver TFEB to up-regulate the expression of the targets Lamp2, Lc3 B, Bcl2, and Atg5(P<0.05). Additionally, ZXD down-regulated the protein level of p-Akt upstream of TFEB in vivo and in vitro. In conclusion, ZXD may promote lipophagy by regulating the Akt/TFEB pathway.


Subject(s)
Autophagy , Drugs, Chinese Herbal , Hepatocytes , Proto-Oncogene Proteins c-akt , Animals , Mice , Autophagy/drug effects , Hepatocytes/drug effects , Hepatocytes/metabolism , Microtubule-Associated Proteins/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Drugs, Chinese Herbal/pharmacology
2.
Zhongguo Zhong Yao Za Zhi ; 47(2): 453-460, 2022 Jan.
Article in Chinese | MEDLINE | ID: mdl-35178989

ABSTRACT

The present study investigated the pharmaceutical effect and underlying mechanism of Zexie Decoction(ZXD) on nonalcoholic fatty liver disease(NAFLD) in vitro and in vivo via the LKB1/AMPK/PGC-1α pathway based on palmitic acid(PA)-induced lipid accumulation model and high-fat diet(HFD)-induced NAFLD model in mice. As revealed by the MTT assay, ZXD had no effect on HepG2 activity, but dose-dependently down-regulated alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver cell medium induced by PA, and decreased the plasma levels of ALT and AST, and total cholesterol(TC) and triglyceride(TG) levels in the liver. Nile red staining showed PA-induced intracellular lipid accumulation, significantly increased lipid accumulation of hepatocytes induced by PA, suggesting that the lipid accumulation model in vitro was properly induced. ZXD could effectively improve the lipid accumulation of hepatocytes induced by PA. Oil red O staining also demonstrated that ZXD improved the lipid accumulation in the liver of HFD mice. JC-1 staining for mitochondrial membrane potential indicated that ZXD effectively reversed the decrease in mitochondrial membrane potential caused by hepatocyte injury induced by PA, activated PGC-1α, and up-regulated the expression of its target genes, such as ACADS, CPT-1α, CPT-1ß, UCP-1, ACSL-1, and NRF-1. In addition, as revealed by the Western blot and immunohistochemistry, ZXD up-regulated the protein expression levels of LKB1, p-AMPK, p-ACC, and PGC-1α in vivo and in vitro. In conclusion, ZXD can improve NAFLD and its mechanism may be related to the regulation of the LKB1/AMPK/PGC-1α pathway.


Subject(s)
Non-alcoholic Fatty Liver Disease , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Alanine Transaminase/metabolism , Animals , Diet, High-Fat , Liver/metabolism , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
3.
J Ethnopharmacol ; 290: 115101, 2022 May 23.
Article in English | MEDLINE | ID: mdl-35151834

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Zexie Tang (ZXT), only two consists with Alismatis Rhizoma (AR) and Atractylodes macrocephala Rhizoma (AM), a classical Chinese medicine formula from Synopsis of the Golden Chamber with a history of 2000 years. Clinical observation in recent years has found that ZXT has excellent lipid-lowering effect. AIM OF THE STUDY: To explore the potential mechanism of ZXT ameliorates hyperlipidemia based on FKBP38/mTOR/SREBPs pathway. MATERIALS AND METHODS: WD-induced hyperlipidemia mice and oleic acid induced cell lipid accumulation model were used to investigate pharmacodynamic. The effect of ZXT on the transcriptional activity of SREBPs was detected by reporter gene assay. Proteins and downstream genes of mTOR/SREBPs pathway were detected in vivo and in vitro. Combined with network pharmacology and HPLC-Q-TOF/MS, the active ingredients were screened and identified. The interaction between active compounds of ZXT and FKBP38 protein were analyzed by docking analysis. RESULTS: ZXT decreased TC, TG and LDL-c levels in blood of WD-induced hyperlipidemia mouse model, and improved insulin resistance in vivo. ZXT also reduced TC, TG and lipid accumulation in cells line, and inhibited SREBPs luciferase activity, protein and its target genes expression such as FASN, HMGCR, etc. Meanwhile, ZXT inhibited protein expression levels of p-mTOR, p-S6K, etc in vitro and in vivo. Combined with network pharmacology and HPLC-Q-TOF/MS, 16 active ingredients were screened and identified. Docking results showed that active compounds of ZXT binding to FKBP38 and formed hydrogen bond. CONCLUSION: Our findings highlighted that ZXT ameliorates hyperlipidemia, in which FKBP/mTOR/SREBPs pathway might be the potential regulatory mechanism.


Subject(s)
Hyperlipidemias/pathology , Lipids/blood , Plant Extracts/pharmacology , Sterol Regulatory Element Binding Proteins/drug effects , TOR Serine-Threonine Kinases/drug effects , Tacrolimus Binding Proteins/drug effects , Alismatales , Animals , Atractylodes , Disease Models, Animal , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred C57BL , Molecular Docking Simulation , Network Pharmacology
4.
J Nat Med ; 75(3): 540-552, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33590347

ABSTRACT

The accumulation of iron-dependent lipid peroxides is one of the important causes of NAFLD. The purpose of this study is to explore the effect of dehydroabietic acid (DA) on ferroptosis in nonalcoholic fatty liver disease (NAFLD) mice and its possible mechanisms. DA improved NAFLD and reduced triglycerides (TG), total cholesterol (TC), and lipid peroxidation level and inhibited ferroptosis in the liver of HFD-induced mice. DA binds with Keap1 to form 3 stable hydrogen bonds at VAL512 and LEU557 and increased nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elemen (ARE) luciferase activity. DA promoted the expression downstream of Nrf2 such as heme oxygenase-1 (HO-1), glutathione (GSH) and its peroxidase 4 (GPX4), so as to eliminate the accumulation of reactive oxygen species (ROS) and reduce lipid peroxides malondialdehyde (MDA) in the liver. DA inhibited ferroptosis and increased the expression of key genes such as ferroptosis suppressor protein 1 (FSP1) in vitro and vivo. In all, DA may bind with Keap1, activate Nrf2-ARE, induce its target gene expression, inhibit ROS accumulation and lipid peroxidation, and reduce HFD-induced NAFLD.


Subject(s)
Abietanes/therapeutic use , Ferroptosis/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Signal Transduction/drug effects , Animals , Antioxidant Response Elements , Cholesterol/blood , Glutathione/metabolism , HEK293 Cells , Heme Oxygenase-1/metabolism , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Lipid Peroxidation/drug effects , Male , Malondialdehyde/metabolism , Membrane Proteins , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Reactive Oxygen Species/metabolism , S100 Calcium-Binding Protein A4/metabolism , Triglycerides/blood
5.
Biomed Pharmacother ; 127: 110155, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32413669

ABSTRACT

Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice.. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro, and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice.


Subject(s)
Abietanes/pharmacology , Fatty Liver/drug therapy , PPAR alpha/agonists , PPAR gamma/agonists , 3T3-L1 Cells , Animals , Cell Line , Diet, High-Fat , Fatty Liver/physiopathology , Humans , Insulin Resistance , Lipid Metabolism/drug effects , Male , Mice , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/metabolism , Oxygen Consumption/drug effects
6.
Sci Rep ; 10(1): 6540, 2020 04 16.
Article in English | MEDLINE | ID: mdl-32300172

ABSTRACT

Clinical reports on hepatotoxicity that arise from Rhizoma Paridis have recently received widespread attention. Because the hepatotoxicity mechanism is little understood, this research strived to investigate the hepatotoxicity mechanism of Rhizoma Paridis extracts based on iTRAQ quantitative proteomics and metabonomics. The extraction solutions were administrated to rats for 7 days by gavage, and the hepatotoxicity was assessed through quantification of biochemical indexes and Oil red O staining. Additionally, the mechanism of hepatotoxicity was investigated by metabonomics based upon GC-MS and iTRAQ quantitative proteomics. The biochemical and histopathological analysis stood out that Rhizoma Paridis extract could induce liver injury, which was proved by the formation of fat droplets, the changes of mitochondrial structure, and biochemical parameters. The iTRAQ proteomics and metabonomics revealed that Rhizoma Paridis-induced hepatotoxicity was chiefly connected with the abnormal activity of mitochondrion function, which brought about oxidative stress injuries and inflammation, finally causing cell apoptosis. Collectively, we have provided previously uncharacterized hepatotoxic mechanism induced by Rhizoma Paridis and a reference to ensure its safe use in the future.


Subject(s)
Liver/metabolism , Liver/pathology , Metabolomics , Proteomics , Rhizome/toxicity , Animals , Discriminant Analysis , Gene Expression Regulation/drug effects , Least-Squares Analysis , Liver/drug effects , Male , Metabolic Networks and Pathways/drug effects , Metabolome/drug effects , Principal Component Analysis , Rats, Sprague-Dawley
7.
J Ethnopharmacol ; 250: 112440, 2020 Mar 25.
Article in English | MEDLINE | ID: mdl-31786445

ABSTRACT

Rhizoma Paridis, as a Traditional Chinese Medicine (TCM), has been used in clinic for thousands of years. Recently, the hepatic toxicity was reported in some published articles while its hepatotoxicity mechanisms have not been well established. Therefore, the present study was performed to determine the effect of Rhizoma Paridis treatment on the lipid deposition and metabolism, oxidative stress and mitochondrial dysfunction, and explore the underlying molecular mechanism through L02 cell, rat and zebrafish larvae. Rhizoma Paridis could diminish cell activity and cell proliferation, brought on cell apoptosis and elevated the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with the control group, as evaluated in cell cultures. Rhizoma Paridis could result in the change of the liver structure and the liver function in the rat model and zebrafish larvae. Our results showed that Rhizoma Paridis could increase hepatic lipid accumulation, which was similar to the previous study and probably exerted toxic effect through intensive fatty acid lipogenesis, inhibition of fat degradation. Meanwhile, this experiment highlighted the importance of the oxidative stress, mitochondrial dysfunction, ER function, and the inflammation response in Rhizoma Paridis-induced disorder of hepatic lipid metabolism, which proposed a novel mechanism for interpretation of Rhizoma Paridis exposure inducing the disorder of lipid metabolism in vertebrates. Furthermore, the result of this experiment suggested that the toxicity response of zebrafish larvae was similar to the conventional model with a significant advantage.


Subject(s)
Chemical and Drug Induced Liver Injury , Melanthiaceae , Plant Extracts/toxicity , Rhizome , Animals , Apoptosis/drug effects , Cell Line , Cell Survival/drug effects , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/pathology , Gene Expression Regulation/drug effects , Larva/drug effects , Lipid Metabolism/drug effects , Liver/drug effects , Liver/pathology , Male , Rats, Sprague-Dawley , Zebrafish
8.
Phytomedicine ; 62: 152959, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31132752

ABSTRACT

BACKGROUND: Euphorbia kansui is effective in treating various diseases, such as ascites and edema, but its liver toxicity is a major obstacle in its wide use in the clinic. However, further investigations have suggested that Euphorbia kansui can cause liver injury. HYPOTHESIS: The study aims to investigate the effect of Euphorbia kansui exposure on zebrafish, and explain the underlying toxicity mechanisms from a comprehensive perspective. STUDY DESIGN: The 4dpf zebrafish larvae were exposed to Euphorbia kansui at a sub-lethal concentration. METHODS: We evaluated the effect of Euphorbia kansui on the ultrastructure and function of the liver, apoptosis of liver cells by PCR and western blot, and metabolic profile by GC-MS based on sub-lethal concentrations. RESULTS: Our results suggested Euphorbia kansui could lead to liver injury and significant alteration of the metabolomics of the zebrafish larvae in sub-lethal concentration conditions. It could also induce alterations in liver microstructure, hepatic function, gene expression and protein associated with the apoptosis process, as well as endogenous metabolism. KEGG pathway analysis identified some biological processes on the basis of different metabolisms and their associated processes especially for amino acid metabolism. CONCLUSION: The results bring us closer to an in-depth understanding of the toxic effects of Euphorbia kansui on zebrafish liver, which will be significantly helpful in effectively guiding safer clinical application of this herb in the clinic. Furthermore, our results also showed the zebrafish model is reliable for evaluation of Euphorbia kansui extract hepatotoxicity and as a methodological reference for the evaluation of Traditional Chinese Medicine with underlying liver toxicity.


Subject(s)
Chemical and Drug Induced Liver Injury/pathology , Metabolome/drug effects , Animals , Apoptosis/drug effects , Cell Death/drug effects , Disease Models, Animal , Euphorbia , Female , Hepatocytes/drug effects , Humans , Larva , Male , Medicine, Chinese Traditional , Metabolomics , Plant Roots/toxicity , Zebrafish
9.
Zebrafish ; 15(6): 610-628, 2018 12.
Article in English | MEDLINE | ID: mdl-30277848

ABSTRACT

Zebrafish larvae were used to further understand the liver toxicity of nux vomica. The histopathology, protein expression, and gene expression were assessed to confirm apoptosis in the liver, and then, profiles of the metabolites in zebrafish were investigated by untargeted metabolomic assessment to understand the potential toxicity mechanism of nux vomica. Histopathological observations showed that nux vomica caused damage to liver cells. Western blot results indicated increased expression of activated caspase3, and the result of real-time polymerase chain reaction showed a significant increase in the expression level of caspase-3, caspase-8, and caspase-9 genes (p < 0.05) compared with the control group. The liver injury from nux vomica was linked to the downregulation of amino acid (e.g., proline and alanine) and fatty acid (e.g., palmitoleic acid) metabolism and upregulation of some other fatty acid (e.g., arachidic acid) and purine (e.g., xanthine and uric acid) metabolism. The hepatotoxicity of nux vomica resulted from metabolic pathway disturbances, including small molecules involved in energy, purine, lipids, and amino acid metabolism.


Subject(s)
Chemical and Drug Induced Liver Injury/metabolism , Metabolome , Plant Extracts/toxicity , Strychnos nux-vomica/toxicity , Zebrafish/growth & development , Animals , Larva/drug effects , Larva/growth & development , Larva/metabolism
10.
Opt Lett ; 43(18): 4429-4432, 2018 Sep 15.
Article in English | MEDLINE | ID: mdl-30211882

ABSTRACT

The ever-increasing global network traffic requires a high level of seamless integration between optical interconnect systems and complementary metal-oxide-semiconductor (CMOS) circuits. Therefore, it brings stringent requirements for future electro-optic (E-O) modulators, which should be ultracompact, energy efficient, high bandwidth, and in the meanwhile, able to be directly driven by the state-of-the-art CMOS circuits. In this Letter, we report a low-voltage silicon photonic crystal nanocavity modulator using an optimized metal-oxide-semiconductor (MOS) capacitor consisting of an In2O3/HfO2/p-Si stacked nanostructure. The strong light-matter interaction from the accumulated free carriers with the nanocavity resonant mode results in holistic improvement in device performance, including a high tuning efficiency of 250 pm/V and an average modulation strength of 4 dB/V with a moderate Q factor of ∼3700 and insertion loss of ∼6 dB using an ultrashort electrode length of only 350 nm. With 1 V driving voltage over a capacitive loading of only 13 fF, the silicon photonic nanocavity modulator can achieve more than 3 dB extinction ratio with energy consumption of only 3 fJ/bit. Such a low-voltage, low-capacitance silicon nanocavity modulator provides the feasibility to be directly driven by a CMOS logic gate for single-chip integration.

11.
Materials (Basel) ; 11(4)2018 Mar 31.
Article in English | MEDLINE | ID: mdl-29614728

ABSTRACT

Diatomaceous earth-otherwise called diatomite-is essentially composed of hydrated biosilica with periodic nanopores. Diatomite is derived from fossilized remains of diatom frustules and possesses photonic-crystal features. In this paper, diatomite simultaneously functions as the matrix of the chromatography plate and the substrate for surface-enhanced Raman scattering (SERS), by which the photonic crystal-features could enhance the optical field intensity. The on-chip separation performance of the device was confirmed by separating and detecting industrial dye (Sudan I) in an artificial aqueous mixture containing 4-mercaptobenzoic acid (MBA), where concentrated plasmonic Au colloid was casted onto the analyte spot for SERS measurement. The plasmonic-photonic hybrid mode between the Au nanoparticles (NP) and the diatomite layer could supply nearly 10 times the increment of SERS signal (MBA) intensity compared to the common silica gel chromatography plate. Furthermore, this lab-on-a-chip photonic crystal device was employed for food safety sensing in real samples and successfully monitored histamine in salmon and tuna. This on-chip food sensor can be used as a cheap, robust, and portable sensing platform for monitoring for histamine or other harmful ingredients at trace levels in food products.

12.
Nano Lett ; 18(2): 1075-1081, 2018 02 14.
Article in English | MEDLINE | ID: mdl-29309164

ABSTRACT

Silicon photonic modulators rely on the plasma dispersion effect by free-carrier injection or depletion, which can only induce moderate refractive index perturbation. Therefore, the size and energy efficiency of silicon photonic modulators are ultimately limited as they are also subject to the diffraction limit. Here we report an ultracompact electro-optic modulator with total device footprint of 0.6 × 8 µm2 by integrating voltage-switched transparent conductive oxide with one-dimensional silicon photonic crystal nanocavity. The active modulation volume is only 0.06 um3, which is less than 2% of the lambda-cubic volume. The device operates in the dual mode of cavity resonance and optical absorption by exploiting the refractive index modulation from both the conductive oxide and the silicon waveguide induced by the applied gate voltage. Such a metal-free, hybrid silicon-conductive oxide nanocavity modulator also demonstrates only 0.5 dB extra optical loss, moderate Q-factor above 1000, and high energy efficiency of 46 fJ/bit. The combined results achieved through the holistic design opened a new route for the development of next generation electro-optic modulators that can be used for future on-chip optical interconnects.

13.
ACS Sens ; 3(1): 230-238, 2018 01 26.
Article in English | MEDLINE | ID: mdl-29262684

ABSTRACT

Surface-enhanced infrared absorption (SEIRA) is capable of identifying molecular fingerprints by resonant detection of infrared vibrational modes through the coupling with plasmonic modes of metallic nanostructures. However, SEIRA for on-chip gas sensing is still not very successful due to the intrinsically weak light-matter interaction between photons and gas molecules and the technical challenges in accumulating sufficient gas species in the vicinity of the spatially localized enhanced electric field, namely, the "hot-spots", generated through plasmonics. In this paper, we present a suspended silicon nitride (Si3N4) nanomembrane device by integrating plasmonic nanopatch gold antennas with metal-organic framework (MOF), which can largely adsorb carbon dioxide (CO2) through its nanoporous structure. Unlike conventional SEIRA sensing relying on highly localized hot-spots of plasmonic nanoantennas or nanoparticles, the device reported in this paper engineered the coupled surface plasmon polaritons in the metal-Si3N4 and metal-MOF interfaces to achieve strong optical field enhancement across the entire MOF film. We successfully demonstrated on-chip gas sensing of CO2 with more than 1800× enhancement factors by combining the concentration effect from the 2.7 µm MOF thin film and the optical field enhancement of the plasmonic nanopatch antennas.


Subject(s)
Gases/analysis , Spectrophotometry, Infrared/methods , Surface Plasmon Resonance , Carbon Dioxide , Equipment Design , Lab-On-A-Chip Devices , Metal-Organic Frameworks , Silicon Compounds
14.
ACS Sens ; 2(3): 346-353, 2017 Mar 24.
Article in English | MEDLINE | ID: mdl-28723214

ABSTRACT

To detect biochemicals with ultrahigh sensitivity, efficiency, reproducibility, and specificity has been the holy grail in the development of nanosensors. In this work, we report an innovative type of photonic-plasmonic hybrid Raman nanosensor integrated with electrokinetic manipulation by rational design, which offers dual mechanisms that enhance the sensitivity for molecule detection directly in solution. For the first time, we integrate large arrays of synthesized plasmonic nanocapsules with densely surface distributed silver (Ag) nanoparticles (NPs) on lithographically patterned photonic crystal slabs via electric-field assembling. With the interdigital microelectrodes, the applied electric fields not only assemble the hybrid plasmonic nanocapsules on photonic crystal slabs, but also generate electrokinetic flows that focus analyte molecules to the Ag hot spots on the nanocapsules for surface-enhanced Raman scattering (SERS) detection. The synergistic effects of plasmonic-photonic resonance and the electrokinetic molecular focusing can promote the SERS enhancement factor (EF) robustly to ∼2 × 109. Various molecules including SERS probing molecules, nucleobases, and unsafe food additives can be detected directly from suspension. The innovative mechanism, design, and fabrication reported in this work can inspire a new paradigm for achieving high-performance Raman nanosensors, which is pivotal for lab-on-chip disease diagnosis and environmental protection.

15.
J Biophotonics ; 10(11): 1473-1484, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28485498

ABSTRACT

Diatomite consists of fossilized remains of ancient diatoms and is a type of naturally abundant photonic crystal biosilica with multiple unique physical and chemical functionalities. In this paper, we explored the fluidic properties of diatomite as the matrix for on-chip chromatography and, simultaneously, the photonic crystal effects to enhance the plasmonic resonances of metallic nanoparticles for surface-enhanced Raman scattering (SERS) biosensing. The plasmonic nanoparticle-decorated diatomite biosilica provides a lab-on-a-chip capability to separate and detect small molecules from mixture samples with ultra-high detection sensitivity down to 1 ppm. We demonstrate the significant potential for biomedical applications by screening toxins in real biofluid, achieving simultaneous label-free biosensing of phenethylamine and miR21cDNA in human plasma with unprecedented sensitivity and specificity. To the best of our knowledge, this is the first time demonstration to detect target molecules from real biofluids by on-chip chromatography-SERS techniques.


Subject(s)
Biosensing Techniques/methods , Chromatography/instrumentation , Diatoms/chemistry , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Biosensing Techniques/instrumentation , Gold/chemistry , Humans , MicroRNAs/blood , Phenethylamines/blood , Spectrum Analysis, Raman
16.
Nanotechnology ; 28(26): 26LT01, 2017 Jun 30.
Article in English | MEDLINE | ID: mdl-28524821

ABSTRACT

In this letter, we present a nanophotonic device consisting of plasmonic nanopatch array (NPA) with integrated metal-organic framework (MOF) for enhanced infrared absorption gas sensing. By designing a gold NPA on a sapphire substrate, we are able to achieve enhanced optical field that spatially overlaps with the MOF layer, which can adsorb carbon dioxide (CO2) with high capacity. Experimental results show that this hybrid plasmonic-MOF device can effectively increase the infrared absorption path of on-chip gas sensors by more than 1100-fold. The demonstration of infrared absorption spectroscopy of CO2 using the hybrid plasmonic-MOF device proves a promising strategy for future on-chip gas sensing with ultra-compact size.

17.
Biosens Bioelectron ; 88: 63-70, 2017 Feb 15.
Article in English | MEDLINE | ID: mdl-27471144

ABSTRACT

We demonstrate a photonic crystal biosilica surface-enhanced Raman scattering (SERS) substrate based on a diatom frustule with in-situ synthesized silver nanoparticles (Ag NPs) to detect explosive molecules from nanoliter (nL) solution. By integrating high density Ag NPs inside the nanopores of diatom biosilica, which is not achievable by traditional self-assembly techniques, we obtained ultra-high SERS sensitivity due to dual enhancement mechanisms. First, the hybrid plasmonic-photonic crystal biosilica with three dimensional morphologies was obtained by electroless-deposited Ag seeds at nanometer sized diatom frustule surface, which provides high density hot spots as well as strongly coupled optical resonances with the photonic crystal structure of diatom frustules. Second, we discovered that the evaporation-driven microscopic flow combined with the strong hydrophilic surface of diatom frustules is capable of concentrating the analyte molecules, which offers a simple yet effective mechanism to accelerate the mass transport into the SERS substrate. Using the inkjet printing technology, we are able to deliver multiple 100pico-liter (pL) volume droplets with pinpoint accuracy into a single diatom frustule with dimension around 30µm×7µm×5µm, which allows for label-free detection of explosive molecules such as trinitrotoluene (TNT) down to 10-10M in concentration and 2.7×10-15g in mass from 120nL solution. Our research illustrates a new paradigm of SERS sensing to detect trace level of chemical compounds from minimum volume of analyte using nature created photonic crystal biosilica materials.


Subject(s)
Diatoms/chemistry , Explosive Agents/analysis , Nanostructures/chemistry , Silicon Dioxide/chemistry , Silver/chemistry , Spectrum Analysis, Raman/methods , Trinitrotoluene/analysis , Biosensing Techniques/methods , Hydrophobic and Hydrophilic Interactions , Limit of Detection , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Nanostructures/ultrastructure , Nanotechnology
18.
IEEE Trans Nanobioscience ; 15(8): 828-834, 2016 12.
Article in English | MEDLINE | ID: mdl-27959817

ABSTRACT

In this paper, we described a new type of bioenabled nano-plasmonic sensors based on diatom photonic crystal biosilica with in-situ growth silver nanoparticles and demonstrated label-free chemical and biological sensing based on surface-enhanced Raman scattering (SERs) from complex samples. Diatoms are photosynthetic marine micro-organisms that create their own skeletal shells of hydrated amorphous silica, called frustules, which possess photonic crystal-like hierarchical micro- & nanoscale periodic pores. Our research shows that such hybrid plasmonic-biosilica nanostructures formed by cost-effective and eco-friendly bottom-up processes can achieve ultra-high limit of detection for medical applications, food sensing, water/air quality monitoring and geological/space research. The enhanced sensitivity comes from the optical coupling of the guided-mode resonance of the diatom frustules and the localized surface plasmons of the silver nanoparticles. Additionally, the nanoporous, ultra-hydrophilic diatom biosilica with large surface-to-volume ratio can concentrate more analyte molecules to the surface of the SERS substrates, which can help to detect biomolecules that cannot be easily adsorbed by metallic nanoparticles.


Subject(s)
Biosensing Techniques/methods , Diatoms/chemistry , Silicon Dioxide/chemistry , Spectrum Analysis, Raman/methods , Photons
19.
Nanoscale ; 8(39): 17285-17294, 2016 Oct 06.
Article in English | MEDLINE | ID: mdl-27714122

ABSTRACT

Novel transducers for detecting an ultra-small volume of an analyte solution play pivotal roles in many applications such as chemical analysis, environmental protection and biomedical diagnosis. Recent advances in optofluidics offer tremendous opportunities for analyzing miniature amounts of samples with high detection sensitivity. In this work, we demonstrate enormous enhancement factors (106-107) of the detection limit for optofluidic analysis from inkjet-printed droplets by evaporation-induced spontaneous flow on photonic crystal biosilica when compared with conventional surface-enhanced Raman scattering (SERS) sensing using the pipette dispensing technology. Our computational fluid dynamics simulation has shown a strong recirculation flow inside the 100 picoliter droplet during the evaporation process due to the thermal Marangoni effect. The combination of the evaporation-induced spontaneous flow in micron-sized droplets and the highly hydrophilic photonic crystal biosilica is capable of providing a strong convection flow to combat the reverse diffusion force, resulting in a higher concentration of the analyte molecules at the diatom surface. In the meanwhile, high density hot-spots provided by the strongly coupled plasmonic nanoparticles with photonic crystal biosilica under a 1.5 µm laser spot are verified by finite-difference time domain simulation, which is crucial for SERS sensing. Using a drop-on-demand inkjet device to dispense multiple 100 picoliter analyte droplets with pinpoint accuracy, we achieved the single molecule detection of Rhodamine 6G and label-free sensing of 4.5 × 10-17 g trinitrotoluene from only 200 nanoliter solution.

20.
Opt Lett ; 41(9): 1913-6, 2016 May 01.
Article in English | MEDLINE | ID: mdl-27128037

ABSTRACT

We demonstrate an ultra-compact, broadband on-chip near-infrared (NIR) spectroscopy system based on a narrow-band plasmonic filter array. The entire filter array, consisting of 28 individual subwavelength metallic gratings, was monolithically integrated in a thin gold film on a quartz substrate, covering a 270 nm spectra from 1510 nm to 1780 nm. In order to achieve a high spectral resolution, extremely narrow slits are created for the gratings with a polymer waveguide layer on top, generating narrow-band guided-mode resonances through coupling with the surface-plasmon resonances of the metallic gratings. Experimental results show that the transmission bands of the filter array have full width at half-maximum of only 7 nm-13 nm, which is sufficient for NIR spectroscopy. The NIR absorption spectroscopy of xylene using the on-chip plasmonic filter array matches very well with the results from conventional Fourier transform infrared spectroscopy, which proves the great potential for NIR sensing applications.

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