Field Of Bioanalysis Research Articles

2D hexagonal SnS2 nanoplates as novel co-reaction accelerator for construction of ultrasensitive g-C3N4-based electrochemiluminescent biosensor

In this work, a highly luminous efficiency methotrexate (MTX) biosensor was successfully prepared with the introduced of SnS2 nanoplates as novel co-reaction accelerator towards amplification electrochemiluminescence (ECL) signal of graphite-like carbon nitride/peroxidisulfate (g-C3N4/K2S2O8) system. Specifically, the SnS2 nanoplates, as an electrochemically regenerable co-reaction accelerator, could accelerate the reduction of S2O82− to produce abundant of sulfate-free radical (SO4·−), evidently enhancing the ECL emitting of g-C3N4. Owing to the reversible electrochemical process of Sn2+ and Sn4+, the regenerable of Sn4+ reactive sites could occur at the surface of electrode, significantly improving the efficiency of co-reaction accelerator. Based upon the excellent quenching effect of MTX towards g-C3N4/K2S2O8 system, the fabricated ECL biosensor manifested high sensitivity with a detection limit of 0.27 pM in the concentration of MTX from 1 pM to 10 μM. More importantly, the constructed biosensor was successfully applied to quantitation of MTX in human serum with favorable results. Consequently, the proposed strategy provided a new sight in the trace determination of MTX in bioanalysis fields.

Paper-Based Constant Potential Electrochemiluminescence Sensing Platform with Black Phosphorus as a Luminophore Enabled by a Perovskite Solar Cell.

Exploring efficient luminophores in the electrochemiluminescence (ECL) system is highly desired to pursue a sensitive ECL sensing platform. Herein, the black phosphorus nanosheets (BP NSs) with excellent ECL properties are investigated and serve as the luminophore with the coreactant of peroxydisulfate (S2O82-) solution. Moreover, owing to the overlapping of emission and absorbance spectra, effective resonance energy transfer (RET) is realized between the BP NSs and the introduced Au nanoparticles. In order to achieve the portable and miniaturized developing trends for the paper-based ECL sensing platform, a paper-based perovskite solar cell (PSC) device is designed to act as the power source to replace the commonly utilized expensive and cumbersome electrochemical workstation. Benefiting from that, a PSC driven paper-based constant potential ECL-RET sensing platform is constructed, thereby realizing sensitive microRNAs (miRNAs) detection. What's more, to attain the preferable analytical performance, the duplex-specific nuclease (DSN) is also introduced to assist the target recycling signal amplification strategy. Based on this, highly sensitive detection of miRNA-107 with a range from 0.1 pM to 15 nM is achieved by this designed sensing platform. Most importantly, this work not only pioneers a precedent for developing a high-sensitivity PSC triggered ECL sensing platform but also explores the application prospect of BP nanomaterial in the field of bioanalysis.

Highly sensitive detection of multiple antibiotics based on DNA tetrahedron nanostructure-functionalized magnetic beads

Functional DNAs-functionalized magnetic beads (MBs) offer great potential in bioanalysis field because of their target recognition and magnetic separation functions. However, the recognition capability and hybridization affinity of DNA probes often suffer from limited available space, poor probe conformation and non-selective adsorption. To overcome these limitations, we herein used aptamer-pendant DNA tetrahedron nanostructure-functionalized MBs (TETapt-tet MBs) to develop a target-response fluorescence method with tetracycline (TET) as a model. In the absence of TET, 6-carboxy-X-rhodamine-labeled complementary DNAs (ROX-cDNAs) were assembled on the surface of MBs. Upon the addition of target TET, the ROX-cDNAs were separated and released from the MBs to generate fluorescence signal. The limit of detection and limit of quantification for TET were found to be 6 pg mL−1 and 20 pg mL−1, respectively. Compared with ssDNA-functionalized MBs surface, the designed DNA tetrahedron nanostructure-based surface could decrease the hybridization time and reduce false positives, ensuring the accuracy of TET detection in complex samples. The presented method was successfully employed for TET detection in honey samples. Moreover, this functionalization strategy could be extended to detect multiple antibiotics by simply substituting different aptamer sequences. Therefore, the proposed method has great potential in the field of food safety and public health.

Chemically Modified Aptamers in Biological Analysis.

Recently, nucleic acid aptamers have been widely used in biological analysis due to their high affinity, binding selectivity, and programmability. Researchers have introduced the idea that chemical modification endows aptamers with rich spatial conformations and functions, extending the application of aptamers in biological analysis. Currently, reviews about aptamers in the bioanalytical field usually focus on the complexes of aptamers and functional materials. Few reviews pay attention to the chemically modified aptamers. In this review, we introduce the synthesis and screening of chemically modified nucleic acids. In addition, we summarize the recent works about chemically modified aptamers in the field of bioanalysis, aiming to provide a promising step toward an aptamer-based versatile platform for biological analysis.

Recent advances in surface-enhanced Raman spectroscopy for the detection of tumor markers

Sensitive and accurate detection of tumor markers is critically essential for the early clinical diagnosis, treatment and prognosis of cancers. Surface-enhanced Raman spectroscopy (SERS) utilizes plasmonic nanomaterials to generate a strong surface plasmon resonance (SPR) effect in the visible to near-infrared region, such as silver and gold nanostructures. The SPR effect can significantly enhance the Raman signals of adsorbed molecules on the surface of nanostructures, allowing to gain the sensitive fingerprint information for the analyte itself or the Raman reporter. Benefitted from the superior properties of high sensitivity, good selectivity, fast and noninvasive analysis, SERS has attracted increasing interest and become a very promising technique for biological analysis. In comparison with other bioanalytical techniques, such as enzyme-linked immunosorbent assay, fluorescence and electrochemical methods, SERS possesses the following advantages: (1) SERS has an ultrahigh sensitivity, even down to single molecule level; (2) SERS can provide the intrinsic molecular fingerprint information, and the bandwidths of SERS peaks are usually very narrow; (3) SERS is suitable for long-term monitoring, because of the resistance of photobleaching and photodegradation; (4) non-invasive detection can be achieved with a low amount of sample and no preparation; (5) the interference of water is very weak, so biological samples can conveniently be detected in aqueous solutions; (6) various SERS-active nanostructures can be designed for multiplex detection. In this review, we provide an overview of recent advances in SERS technology for the detection of different tumor markers, including proteins, enzymes, nucleic acids, cells, tissues, gases and others. Great successes have been achieved by utilizing SERS, which can facilitate the fabrication of assays for tumor biomarkers. However, SERS has not been widely applied in clinical bioanalysis and biodiagnosis in the past over 40 years. SERS-based bioassay involves complex interactions between light, surface plasmon nanomaterials, and bioassay systems. It is difficult to obtain reproducible and reliable Raman spectroscopy data, which is one of the main bottlenecks in SERS bioassay, resulting in the deficiency of clinical and standardized applications. Therefore, there are still many efforts to be done to control the potential factors: (1) It is necessary to prepare a SERS substrate with high uniformity, high enhancement, clean, or/and to properly modify its surface; (2) the suitable Raman reporters and tags are selected to improve the biocompatibility and avoid unspecific adsorption, which can trap analytes in the “hot spots”; (3) biological samples are retained in their native state during the storage and pretreatment procedure to avoid irreversible degradation; (4) appropriate SERS detection conditions are performed, such as excitation wavelength, exposure time, and laser power, to obtain real detection information; (5) accurate biomolecule database are established for spectral assignments. By further improving these challenges, we anticipate the more widespread application of SERS-based assay in biomedicine and bioanalysis fields.

Recent advances and trends in miniaturized sample preparation techniques.

Advances in the area of sample preparation are significant and have been growing significantly in recent years. This initial step of the analysis is essential and must be carried out properly, consisting of a complicated procedure with multiple stages. Consequently, it corresponds to a potential source of errors and will determine, at the end of the process, either a satisfactory result or a fail. One of the advances in this field includes the miniaturization of extraction techniques based on the conventional sample preparation procedures such as liquid-liquid extraction and solid-phase extraction. These modern techniques have gained prominence in the face of traditional methods since they minimize the consumption of organic solvents and the sample volume. As another feature, it is possible to reuse the sorbents, and its coupling to chromatographic systems might be automated. The review will emphasize the main techniques based on liquid-phase microextraction, as well as those based upon the use of sorbents. The first group includes currently popular techniques such as single drop microextraction, hollow fiber liquid-phase microextraction, and dispersive liquid-liquid microextraction. In the second group, solid-phase microextraction techniques such as in-tube solid-phase microextraction, stir bar sorptive extraction, dispersive solid-phase extraction, dispersive micro solid-phase microextraction, and microextraction by packed sorbent are highlighted. These approaches, in common, aim the determination of analytes at low concentrations in complex matrices. This article describes some characteristics, recent advances, and trends on miniaturized sample preparation techniques, as well as their current applications in food, environmental, and bioanalysis fields.

A portable solar-driven ratiometric photo-electrochromic visualization biosensor for detection of ochratoxin A

Photoelectrochemical (PEC) biosensors have been widely studied and applied due to unique advantages. But the requirement of electrochemical workstation and light source limits the development of portable PEC biosensors. In this work, a portable solar-driven visualization PEC biosensor has been successfully developed to completely get rid of instruments requirement. This biosensor is fabricated onto a small ITO electrode which may be divided into two modules, one is the detection module and the other is the reference module. Each module is composed of two regions. Co, N-TiO2/3DGH (three-dimensional graphene hydrogel) nanocomposite is used to construct the photoelectric sensing region and the electrochromic material Prussian Blue (PB) is used in the visual region. The quantification is through the chromaticity ratio of visual regions on the two modules. Based on this, the proposed portable visual biosensor has been successfully applied to the detection of ochratoxin A (OTA). A good linear range (1 ng/mL–500 ng/mL) was obtained with a detection limit of 0.29 ng/mL. Due to its high accuracy and portability, the sensor will bring bright prospects for research in the fields of bioanalysis, food testing and so on.

Quantitative analysis of underivatized 17 β-estradiol using a high-throughput LC–MS/MS assay – Application to support a pharmacokinetic study in ovariectomized guinea pigs

Difference in female sex hormone, β-estradiol (E2), levels can contribute to sex differences in biological processes that underlie target tissue functions (QT interval), vulnerability to diseases (hepatitis or HIV), and response toward therapies. Accurate quantification of plasma E2 level is thus an important aspect in both basic science research examining hormone-regulated physiological mechanisms and in clinical settings to support patient care associated with altered E2 levels. Due to lack of a high-throughput high-sensitivity analytical method, we developed and validated a LC–MS/MS assay for accurate low-level quantification of E2 and demonstrated its application to a guinea pig pharmacokinetic study in which guinea pigs were treated with 10 or 40 μg/kg E2 subcutaneously and blood samples collected at 0 (pre-dose), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 h post-dosing. E2 was extracted using 90 μL ovariectomized guinea pig plasma by liquid-liquid extraction. The method was robust, sensitive with linear range from 3.9 to 1000 pg/mL, and the assay met acceptance criteria for validation parameters listed in the current FDA Guidance on Bioanalytical Method Validation. Compared to the 10 μg/kg dose, more than dose proportional increase in maximum E2 plasma concentration (Cmax) and AUC0-∞ and correspondingly longer half-life were observed after 40 μg/kg dose. This assay is a significant improvement over existing E2 quantification methods in bioanalytical field, with high precision and accuracy, low sample and injection volumes, no derivatization, and short assay run time of 3 min. This assay is amenable in high-throughput settings requiring low-level E2 quantitation in basic science research and clinical settings.

Recent Applications of Molecularly Imprinted Sol-Gel Methodology in Sample Preparation.

Due to their selectivity and chemical stability, molecularly imprinted polymers have attracted great interest in sample preparation. Imprinted polymers have been applied for the extraction and the enrichment of different sorts of trace analytes in biological and environmental samples before their analysis. Additionally, MIPs are utilized in various sample preparation techniques such as SPE, SPME, SBSE and MEPS. Nevertheless, molecularly imprinted polymers suffer from thermal (stable only up to 150 °C) and mechanical stability issues, improper porosity and poor capacity. The sol-gel methodology as a promising alternative to address these limitations allowing the production of sorbents with controlled porosity and higher surface area. Thus the combination of molecularly imprinted technology and sol-gel technology can create influential materials with high selectivity, high capacity and high thermal stability. This work aims to present an overview of molecularly imprinted sol-gel polymerization methods and their applications in analytical and bioanalytical fields.

Perspectives on the draft ICH-M10 guidance: an interview with Mark Arnold.

Biography Mark E Arnold, PhD, is Director of Science for Covance Laboratories. In that role, he develops the bioanalytical strategy for immune-, cell-based, quantitative polymerase chain reaction(qPCR) and LC-MS/MS assays to quantify drugs and metabolites, antidrug antibodies and biomarkers in animal and clinical samples for pharmacokinetic and pharmacodynamic assessments. Mark was previously Executive Director of Bioanalytical Sciences at Bristol-Myers Squibb. He received a BS (biology) from Indiana University of Pennsylvania and PhD (pharmacology) from the University of Pittsburgh. For more than 30years, Mark has been involved in the evolving field of bioanalysis, including the science and the review and interpretation of regulations and guidance. He co-chaired the AAPS Crystal City V and VI Workshops on the US 'FDA Draft Revised Guidance on Bioanalytical Method Validation' and 'Biomarkers'. He is actively involved in the Land O'Lakes Bioanalytical Conference and American Association of Pharmaceutical Scientists (AAPS, named Fellow in 2014).Mark has over 100 peer-reviewed publications, and numerous invited podium presentations. This interview was conducted by Sankeetha Nadarajah, Managing Commissioning Editor of Bioanalysis.

The Role of Electrochemical Immunosensors in Clinical Analysis.

An immunosensor is a kind of affinity biosensor based on interactions between an antigen and specific antigen immobilized on a transducer surface. Immunosensors possess high selectivity and sensitivity due to the specific binding between antibody and corresponding antigen, making them a suitable platform for several applications especially in the medical and bioanalysis fields. Electrochemical immunosensors rely on the measurements of an electrical signal recorded by an electrochemical transducer and can be classed as amperometric, potentiometric, conductometric, or impedimetric depending on the signal type. Among the immunosensors, electrochemical immunosensors have been more perfected due to their simplicity and, especially their ability to be portable, and for in situ or automated detection. This review addresses the potential of immunosensors destined for application in clinical analysis, especially cancer biomarker diagnosis. The emphasis is on the approaches used to fabricate electrochemical immunosensors. A general overview of recent applications of the developed electrochemical immunosensors in the clinical approach is described.

Multi-hydrogen bond assisted SERS detection of adenine based on multifunctional graphene oxide/poly (diallyldimethyl ammonium chloride)/Ag nanocomposites

Nanocomposites of graphene oxide/poly (diallyldimethyl ammonium chloride)/Ag nanoparticles (GO/PDDA/Ag NPs) were constructed via a self–assembly process as a surface-enhanced Raman scattering (SERS) substrate, in which functional macromolecules PDDA were utilized to load GO and support Ag NPs. Fundamental SERS performance of this SERS substrate was evaluated using rhodamine 6G (R6G), which displayed excellent enhancement effect, transferable nature and high stability of the synthesized GO/PDDA/Ag NPs substrate. Furthermore, the synthesized SERS substrate was employed in the sensitive detection of adenine with a linear range of 0.05–1000 μM and low detection limit of 1 nM. Other than the large surface area of GO, multiple-hydrogen bond interactions between adenine and the modified PDDA were another important factor in capturing adenine molecules and enhancing SERS signal. The hydrogen bond interaction was calculated using quantum mechanical calculations. Moreover, determination of adenine in aqueous solutions was achieved with good anti-interference ability against other nucleic bases with similar structures, such as guanine, cytosine and thymine. Therefore, GO/PDDA/Ag can be anticipated to be a potential substrate for label-free, fast and sensitive SERS detection of adenine in the field of bioanalysis.

Liquid-phase microextraction in 96-well plates - calibration and accurate quantification of pharmaceuticals in human plasma samples

The use of miniaturized systems with the possibility for automation has become increasingly popular in the field of bioanalysis. As a new approach to liquid phase microextraction in the 96-well format, parallel artificial liquid membrane extraction (PALME) was introduced in 2013. In the present work, the reliability of the quantitative data obtained with PALME was thoroughly evaluated. Amitriptyline, nortriptyline, quetiapine, venlafaxine, o-desmethylvenlafaxine, and fluoxetine were selected as model analytes. The analytes were extracted under non-exhaustive conditions from human plasma samples and the extracts were analyzed directly by LC-MS/MS. Accuracy was within ±15% and precision was <15% when the QC samples were prepared in both pooled plasma and in plasma from multiple sources. Accuracy and precision was superior when stable isotopically labelled (SIL) internal standards were used, as compared to structural analogue internal standards in the plasma samples from multiple sources. SIL internal standards are therefore recommended as the first choice. Assessment of accuracy and precision was also carried out with four different operators performing the extraction procedure, providing accuracy within ±15% and precision <15%. The extraction recoveries were in the range from 48 to 85 %, and non-exhaustive extraction of the analytes did not affect the accuracy and precision of the method. With the method described, up to 96 samples can be extracted with a total extraction time of 60 min and with a total consumption of organic solvent less than 0.4 mL for the whole wellplate. PALME is therefore a new approach to high-throughput sample preparation, providing accurate quantification, along with simple workflow, low consumption of organic solvent, and extensive sample clean-up.

Ruthenium complex doped metal-organic nanoplate with high electrochemiluminescent intensity and stability for ultrasensitive assay of mucin 1

In this study, a novel Ru(bpy)2(dcbpy)-doped two-dimensional (2D) metal-organic framework (MOF) nanoplate (Ru@Zr12-BPDC, BPDC = 4,4′-biphenyldicarboxylate, bpy = 2,2'-bipyridine, H2dcbpy = 2,2'-bipyridine-5,5'-dicarboxylic acid) with outstanding ECL performance was synthesized via a mixed ligand strategy. The matching lengths between Ru(bpy)2(dcbpy) and BPDC ligands allowed the Ru(bpy)2(dcbpy) to bridge two Zr12 clusters of Ru@Zr12-BPDC nanoplate through strong coordination bonds, which not only resulted in the increase of the immobilization amount of Ru(bpy)2(dcbpy), but also prevented the leakage of the Ru(bpy)2(dcbpy) effectively. Furthermore, the high porosity and ultrathin nature of 2D Ru@Zr12-BPDC nanoplate not only allowed the electrochemical activation of the internal and external Ru(bpy)2(dcbpy), but also greatly shortened the diffusion paths of the ions, electrons, coreactant (tripropylamine, TPrA) and coreactant intermediates (TPrA• and TPrA•+), which made more interior Ru(bpy)2(dcbpy) could be excited and thus led to the increasing utilization ratio of the luminophores. Because of the above merits, the Ru@Zr12-BPDC nanoplate exhibited high and stable ECL emission, and thus was employed to construct an aptasensor for ultrasensitive detection of mucin 1 (MUC1). To further enhance the sensitivity of the proposed aptasensor and amplify signal, the target MUC1 was converted into the H1-H2 duplex with the assistance of H1, H2 and MUC1-catalyzed hairpin assembly (CHA). As expected, the proposed aptasensor exhibited remarkable stability, excellent sensitivity, high sensitivity and displayed a wide liner range from 1 fg/mL to 10 ng/mL with a low detection limit of 0.14 fg/mL. To our knowledge, it is the first example of the construction of an ECL biosensor based on ruthenium complex doped 2D MOF nanoplates. This study demonstrated that the use of ruthenium complex doped MOF nanoplates to increase the ECL stability and intensity is an efficient strategy for the construction of highly stable and sensitive ECL biosensors, and therefore may extend the applications of 2D MOF nanoplates in ECL and bioanalysis fields.

An FPSE-HPLC-PDA method for rapid determination of solar UV filters in human whole blood, plasma and urine

This paper reports a novel fabric phase sorptive extraction-high performance liquid chromatography-photodiode array detection (FPSE-HPLC-PDA) method for the simultaneous extraction and analysis of six benzophenone derivative UV filters including benzophenone (BZ); 5-benzoyl-4-hydroxy-methoxybenzenesulfonic acid (BP-4); bis(4-hydroxyphenyl)methanone (4-DHB); bis(2,4-dihydroxyphenyl)methanone (BP-2); (2,4-dihydroxybenzophenone) (BP-1) and 2,2′-dihydroxy-4-methoxybenzophenone (DHMB) in human whole blood, plasma and urine samples.Chromatographic separation method was conducted using a Spherisorb ODS 1 (C18) column in isocratic elution mode with a run time <25 min. The FPSE-HPLC-PDA method was validated in the range from 0.1 to 10 μg/mL for all the UV filter compounds. Propyl 4-hydroxybenzoate (also known as propyl paraben) was used as the internal standard (IS). The limit of quantification was found to be 0.1 μg/mL and the weighted-matrix matched standard calibration curves of six UV filters showed a good linearity up to a concentration of 10 μg/mL.This new approach exhibits high potential for direct adaptation as a rapid, robust and green analytical tool for several applications, e.g. in the current sample preparation practices used in many bioanalytical fields including pharmacokinetics (PK), pharmacodynamics (PD), therapeutic drug monitoring (TDM), clinical and forensic toxicology, disease diagnosis and drug discovery. Additionally, in the present work was highlighted that applying innovative extraction and clean up procedures before instrumental analysis by means of a well-known, rugged, cheap, and diffused configurations (e.g. HPLC-PDA), could be possible to validate methods that shows analytical performances comparable to more expensive and complex instrumentations (e.g. LC-MS/MS) that require trained personnel, high maintenance costs and a deep knowledge of analytical problems that could be encountered.

An ultrasensitive electrochemiluminescence biosensor for MicroRNA detection based on luminol-functionalized Au NPs@ZnO nanomaterials as signal probe and dissolved O2 as coreactant

In this work, the ZnO nanostars with excellent catalytic performance were firstly used as the coreaction accelerator of luminol-O2 system to construct a biosensor for ultrasensitively detecting microRNA-21 (miRNA-21) in cancer cells. Specifically, ZnO nanostars could expedite the reduction of dissolved O2, generating more reactive oxygen species (ROSs) to extremely promote electrochemiluminescence (ECL) luminous efficiency of luminol. Thus luminol-functionalized Au NPs@ZnO (L-Au NPs@ZnO) nanomaterials were employed as signal probe to fabricate sensing nano-platform for achieving significant ECL emission as “signal on” state. Moreover, upon the addition of a tiny minority of target miRNA-21, massive ferrocene (Fc) could be immobilized on the sensing interface through hybridization chain reaction (HCR) triggered-DNA dendrimers self-assembly, in which Fc consumed dissolved O2 for prominently quenching the ECL emission of signal probe and then reached a “signal off” state. As a result, the biosensor performed a good linearity in 100 aM – 100 pM and a low limit of detection (LOD) down to 18.6 aM. In general, this work utilized a new coreaction accelerator as an efficient amplification approach for ultrasensitively detecting target analyses, providing a promising approach in luminol-centric ECL bioanalysis fields.

Perspectives on Gender Parity in Bioanalysis: An Interview with Stephanie Cape

Stephanie Cape, is the Director of Bioanalytical Science at Covance, Madison, WI, USA. She received her BS in Chemistry from University of IL- Urbana/Champaign in 2003 and her PhD in Analytical Chemistry from the University of Wisconsin - Madison in 2007. Dr Cape's graduate research was focused on developing high-resolution mass spectrometric methods to enable discovery, characterization, imaging and quantitation of neuropeptides. Stephanie joined the field of regulated bioanalysis as a method development/validation chemist initially at PPD and subsequently at Covance. Within the Covance Bioanalytical team, she has held a variety of leadership roles including oversight of bioanalytical study direction, validation and method development. Additionally, Dr Cape is an active member of the broader scientific community through involvement in multiple industry groups focused on global best practices and innovation in the field of bioanalysis.

Reflecting on Bioanalysis with the Senior Editors.

A previous Senior Editor, and the present Senior Editor of Bioanalysis reflect on their journeys in the field of bioanalysis, and with the journal. They discuss the evolution and progress of journal since its launch 10years ago, and where they would like to see it heading in the future.

Simultaneous high-performance liquid chromatography with tandem mass spectrometry quantification of six bioactive components in rat plasma after oral administration of Yougui pill.

Yougui pills are a classic Chinese medicine that shows significant effects on nerve regeneration and neuroprotection in modern pharmacological studies. With a complex formula, Yougui pills have faced significant challenges in the fields of bioanalysis and pharmacokinetics in animals and human studies. In the present study, a specific and accurate high-performance liquid chromatography with tandem mass spectrometry method was developed and validated for the quantitative determination of the six bioactive components in rat plasma after oral administration of Yougui pills. Chromatographic separation was performed on a C18 column with a gradient elution system. Samples were analysed using positive ion mode with multiple reaction monitoring mode. The assay showed good linearity for all six bioactive components in the dynamic range of 0.50 to 50ng/mL with acceptable intra- and inter-batch accuracy and precision. The lower limits of quantification were 0.50ng/mL for all six bioactive components. The method was successfully applied to rat pharmacokinetics after oral administration of Yougui pills. All six bioactive components were detected in rat plasma, including songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline, and sweroside, while some other target compounds were not detected, such as rhmannioside A, loganin, and cornuside I. After oral administration of Yougui pills at a dose of 2500mg/kg, all six bioactive components were rapidly absorbed, resulting in tmax values less than 1h and relative lower Cmax values. The t1/2 values for songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline, and sweroside were calculated to be 2.62±0.67, 2.11±0.45, 1.94±0.35, 1.88±0.31, 2.07±0.44, and 1.59±0.30h, which indicated that Yougui pills should be taken in multiple oral doses over a relatively short period.

Boosting Light Collection Efficiency of Optical Fibers Using Metallic Nanostructures

Optical fibers represent one of the most important photonic components with applications in numerous fields; however, their performance with respect to light collection at large incident angles is severely limited. Here, we show that arrays of metallic nanodots located on the end faces of regular step index fibers allow addressing incoupling angles up to 80° at high efficiencies, representing a regime in which bare fibers fail to operate. The experimental demonstrations including lithographic implementation and optical characterization supported by corresponding numerical simulations and a toy model reveal the feasibility and potential of the concept of nanostructure-enhanced fiber incoupling, which is compatible with other types of nanostructures and can lead to significant improvements, particularly in the fields of bioanalytics and quantum technologies.