A novel fluorescence sensor based on molybdenum‐doped carbon quantum dots (Mo‐CQDs) was developed to determine lemon yellow in beverages. Mo‐CQDs were prepared from β‐cyclodextrin(carbon source) and ammonium molybdate through a bottom‐up, one‐step hydrothermal synthesis. The composition and structure of Mo‐CQDs were determined using transmission electron microscopy, x‐ray energy spectrum analysis, and FT‐IR. The amount of Mo‐CQDs involved in the reaction and the pH of the system were optimized to determine the optimal reaction conditions. A quantitative standard curve was established based on the quenching effect of lemon yellow on Mo‐CQDs, allowing the determination of lemon yellow in beverage samples. The experimental results show that Mo‐CQDs were successfully prepared at 180°Cover 24 h, exhibiting good optical properties. Lemon yellow effectively quenches the Mo‐CQDs fluorescence peak at 460 nm when excited at 330 nm in a phosphate buffer solution (PBS, pH = 6.0). The quenching degree of Mo‐CQDs presents a good linear relationship between 0.10 and 100.00 μmol/L ( R 2 = 0.9955), and the detection limit is 0.03 μmol/L ( S / N = 3). The average recovery rate in actual samples was 102.05%, and the relative standard deviation was 0.72%. The results were consistent with those obtained using HPLC, demonstrating satisfactory determination of lemon yellow content in various beverages, suggesting a good application prospect.

Bisphenols, as common industrial raw materials, are widely used in food packaging such as plastics. However, their migration and residue may affect the hormone secretion of the human body and then lead to health problems. Therefore, a low-cost, rapid and simple detection method that can simultaneously detect multiple bisphenols is very necessary. In this work, two types of manganese single-atom nanozymes with excellent peroxidase-like activity were synthesized with graphyne as a support. A high-throughput colorimetric sensor array was constructed using three types of nanozymes (Mn-GY, Mn-GY-2N, GY-2N) to distinguish various bisphenols. Due to the absorption of bisphenol molecules on the surface of nanozymes, the activity of nanozymes decreases differently, when different bisphenols are added to the catalytic system. The results proved that the prepared sensor had good linear relationships at both low and high concentrations for determination of five bisphenols. The LODs of BPA, BPS, BPF, BPAF, and Diphenolic Acid were 0.443, 0.280, 0.277, 0.424, and 0.326 mu M respectively. Compared with traditional sensors, the sensor array can simultaneously detect multiple analytes with high throughput, showing great advantage in dealing with complex samples. Combined with machine learning algorithms, five bisphenols can be successfully identified by the obtained array data. The sensor array also demonstrated excellent performance in the detection of both mixed samples and real samples. This high- throughput colorimetric sensor array achieves accurate and sensitive detection of bisphenol substances, providing new means and ideas for enhancing food safety. At the same time, the simple and rapid identification of structurally similar compounds demonstrates its potential for more precise analysis, providing possibilities for future development.

Biomolecular condensates exhibit distinct microenvironments that arise from interactions between proteins, RNA, and solutions. In aqueous solutions, these membraneless structures constantly encounter small molecules that could affect the structure and properties of the condensates. However, the effects of organic small molecules in water solutions on the microenvironments of condensates remain poorly understood. In this study, we used various organic solutes as an example to explore how small molecules could influence the physicochemical properties in the microenvironment of protein condensates. Particularly, we quantitatively studied micropolarity and microviscosity using a combination of techniques, including fluorescence lifetime imaging microscopy, fluorescence recovery after photobleaching, and passive rheology. Unexpectedly, our results revealed that the microenvironment was not correlated with the polarity of organic solutes; instead, the correlation was observed on the interaction strength between water and small molecules. We found that solutes with stronger interaction with water and weaker interaction with proteins increase the micropolarity and decrease the microviscosity of condensates. Furthermore, we demonstrated that the modulation of the micropolarity of condensates could impact the miscibility of multicomponent condensates. Finally, we showed that organic solutes could influence the micropolarity of condensates and the partitioning of products in condensates, thus affecting the rate and equilibrium of the chemical reactions. In summary, our work provides a quantitative analysis of how the microenvironment of biomolecular condensates is impacted by organic solutes. Since protein condensates coexist with various types of metabolites in the aqueous cellular milieu, results from this work offer insights into how organic metabolites could regulate the microenvironment and behaviors of biological condensates.

Surgical reattachment of tendon to bone is the standard therapy for rotator cuff tear (RCT), but its effectiveness is compromised by retear rates of up to 94%, primarily due to challenges in achieving successful tendon-bone enthesis regeneration under natural conditions. Biological augmentation using biomaterials has emerged as a promising approach to address this challenge. In this study, a bilayer construct incorporates polydopamine (PDA)-mediated bone morphogenetic protein 2 (BMP2) and BMP12 in separate poly(lactic-co-glycolic acid) (PLGA) fiber layers to promote osteoblast and tenocyte growth, respectively, and intermediate fibrocartilage formation, aiming to enhance the regenerative potential of tendon-bone interfaces. The lower layer, consisting of PLGA fibers with BMP2 immobilization through PDA adsorption, significantly accelerated osteoblast growth. Concurrently, the upper BMP12@PLGA-PDA fiber mat facilitated fibrocartilage formation and tendon tissue regeneration, evidenced by significantly elevated tenocyte viability and tenogenic differentiation markers. Therapeutic efficacy assessed through in vivo RCT models demonstrated that the dual-BMP construct augmentation significantly promoted the healing of tendon-bone interfaces, confirmed by biomechanical testing, cartilage immunohistochemistry analysis, and collagen I/II immunohistochemistry analysis. Overall, this combinational strategy, which combines augmentation patches with the controlled release of dual growth factors, shows great promise in improving the overall success rates of rotator cuff repairs.

Compared with traditional "lock-key mode" biosensors, a sensor array consists of a series of sensing elements based on intermolecular interactions (typically hydrogen bonds, van der Waals forces, and electrostatic interactions). At the same time, sensor arrays also have the advantages of fast response, high sensitivity, low energy consumption, low cost, rich output signals, and imageability, which have attracted widespread attention from researchers. Nanozymes are nanomaterials which own enzyme-like properties. Because of the adjustable activity, high stability, and cost effectiveness of nanozymes, they are potential candidates for construction of sensor arrays to output different signals from analytes through the chemoresponse of colorants, which solves the shortcomings of traditional sensors that they cannot support multiple detection and lack universality. Recently, a sensor array based on nanozymes as nonspecific recognition receptors has attracted much more attention from researchers and has been applied to precise recognition of proteins, bacteria, and heavy metals. In this perspective, attention is given to nanozymes and the regulation of their enzyme-like activity. Particularly, the building principles and methods for sensor arrays based on nanozymes are analyzed, and the applications are summarized. Finally, the approaches to overcome the challenges and perspectives are also presented and analyzed for facilitating further research and development of nanozyme sensor arrays. This perspective should be helpful for gaining insight into research ideas within the field of nanozyme sensor arrays.

Acute neuroinflammation, which is notably characterized by a significant elevation in pro-inflammatory cytokines and chemokines, often rapidly develops following a traumatic spinal cord injury and exacerbates damage in the lesion area. This study addresses the limitations inherent in strategies that regulate only a single or a few cytokines, which are often insufficient to counteract the progression of secondary injuries. We explore the use of polydopamine nanoparticles as a broad-spectrum immunomodulator, capable of capturing by adsorption a wide range of cytokines and thereby effectively suppressing neuroinflammation. Leveraging their adhesive properties, these nanoparticles promptly reduce levels of various excessive cytokines, including IL-1α, IL-1β, IL-6, IL-10, IL-17A, IL-18, TNF-α, MCP-1, GRO/KC, M-CSF, MIP-3α, and IFN-γ, primarily through physical adsorption. This reduction in cytokine levels contributes to the subsequent inhibition of pro-inflammatory M1 microglia and A1 astrocyte activation, aiding in the recovery of motor functions in vivo. In summary, polydopamine nanoparticles represent a versatile and effective approach for modulating acute neuroinflammation in spinal cord injuries. By broadly down-regulating cytokines, polydopamine nanoparticles propose an innovative approach for treating spinal cord injuries. Statement of significance The current study demonstrated the immunomodulatory potential of polydopamine nanoparticles in mitigating neuroinflammation following spinal cord injury. Both in vitro and in vivo analyses revealed significant downregulation of several key cytokines among a panel of 23 cytokines and chemokines. The potential underlying mechanisms governing these interactions were elucidated through comprehensive molecular dynamics simulations for the first time. Consequently, the downregulation of these cytokines and chemokines led to the inhibition of pro-inflammatory M1 microglia and A1 astrocyte activation in both in vitro and in vivo models. This inhibition protected neurons within the microenvironment, resulting in improved locomotor functions. Overall, this study underscores the prominent therapeutic efficacy of polydopamine nanoparticles in alleviating neuroinflammation, highlighting their potential as broad-spectrum regulators in intricate microenvironments.

The coordination number of metal single-atoms, being an important factor, should be precisely controlled as it affects both activity and specificity. Herein, the introduction of nitrogen into the para position of benzene in graphyne (2N-GY) is proposed as a carrier for anchoring metal single-atoms onto pyrazine nitrogen. These atoms are then coordinated to the center of the rhombic cavity, ensuring precisely controlled coordination numbers. Inspired by natural enzymes, a series of transition metal single-atom nanozymes (SANs) are constructed utilizing 2N-GY. Both theory calculations and experiments demonstrated that the incorporation of metal single-atoms of Fe, Mn, and Mo effectively augmented the enzyme-like activity, with Mo/GY exhibiting the highest peroxidase -like activity. Based on the differing activities of M/GY (M = Fe, Mn, Mo) and the varying abilities of sulfhydryl groups in biothiols to occupy metal active sites, sensing arrays for the high-throughput identification of six biothiols are constructed. After combining the fingerprint feature responses of biothiols and SANs with machine learning algorithms, the efficient distinction of the six biothiols is achieved. This study introduces a novel pathway for designing and synthesizing SANs that mimic natural enzymes.

Natural enzymes are crucial in biological systems and widely used in biology and medicine, but their disadvantages, such as insufficient stability and high-cost, have limited their wide application. Since Fe3O4 nanoparticles were found to show peroxidase-like activity, researchers have designed and developed a growing number of nanozymes that mimic the activity of natural enzymes. Nanozymes can compensate for the defects of natural enzymes and show higher stability with lower cost. Iron, a nontoxic and low-cost transition metal, has been used to synthesize a variety of iron-based nanozymes with unique structural and physicochemical properties to obtain different enzymes mimicking catalytic properties. In this perspective, catalytic mechanisms, activity modulation, and their recent research progress in sensing, tumor therapy, and antibacterial and anti-inflammatory applications are systematically presented. The challenges and perspectives on the development of iron-based nanozymes are also analyzed and discussed.

Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8–63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 μg) within the limited administration volume (10 μL) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.

Electrospun organic/inorganic hybrid scaffolds have been appealing in tissue regeneration owing to the integrated physicochemical and biological performances. However, the conventional electrospun scaffolds with non-woven structures usually failed to enable deep cell infiltration due to the densely stacked layers among the fibers. Herein, through self-assembly-driven electrospinning, a polyhydroxybutyrate/poly(e-caprolactone)/58S sol-gel bioactive glass (PHB/PCL/58S) hybrid scaffold with honeycomb-like structures was prepared by manipulating the solution composition and concentration during a one-step electrospinning process. The mechanisms enabling the formation of self-assembled honeycomb-like structures were investigated through comparative studies using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) between PHB/PCL/58S and PHB/PCL/sol-gel silica systems. The obtained honeycomb-like structure was built up from nanofibers with an average diameter of 370 nm and showed a bimodal distribution of pores: large polygonal pores up to hundreds of micrometers within the honeycomb-cells and irregular pores among the nanofibers ranging around few micrometers. The cell-materials interactions were further studied by culturing MG-63 osteoblast-like cells for 7 days. Cell viability, cell morphology and cell infiltration were comparatively investigated as well. While cells merely proliferated on the surface of non-woven structures, MG-63 cells showed extensive proliferation and deep infiltration up to 100-200 mu m into the honeycomb-like structure. Moreover, the cellular spatial organization was readily regulated by the honeycomb-like pattern as well. Overall, the newly obtained hybrid scaffold may integrate the enhanced osteogenicity originating from the bioactive components, and the improved cell-material interactions brought by the honeycomb-like structure, making the new scaffold a promising candidate for tissue regeneration.

CuO-NiO nanocomposites have been prepared after calcining fiber mats at 450 degrees C by electrospinning technique. The samples are characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. SEM micrographs depict regular nanofibers without beads. The XRD and TEM results confirm that as-synthesized materials are the composite nanoparticles composed of the crystal phases of CuO and NiO. An enzyme-free glucose sensor has been first fabricated with nanocomposites CuO-NiO-modified on glassy carbon electrode (GCE). Cyclic voltammetry and current-time curve techniques are mainly used to enlighten the electrochemical properties of the modified electrode (CuO-NiO/GCE) in alkaline aqueous solutions. Experimental parameters like applied potential and concentration of modifier on GCE have been optimized, and the analytical performances of as-fabricated biosensor for glucose determination have been investigated in detail. Under optimal conditions (8.0 mu L modifier, +0.55 V), CuO-NiO/GCE exhibits excellent properties in glucose detection for the concentrations with a fast response (similar to 1s), a low detection limit of 0.08 mu M (S/N = 3), a wide range of 0.2 mu M-1.0 mM with a linear correlation coefficient of 0.998 and a very high sensitivity of 4022 mu A mM(-1) cm(-2). In addition CuO-NiO/GCE shows good selectivity, reproducibility and longtime stability. Excellent electrochemical catalytic performance for glucose demonstrates that as-synthesized nanocomposite CuO-NiO is an outstanding and promising electrode material toward glucose.

Curcumin is used as a natural pigment and flavoring agent and food additive in food processing industries. Also, curcumin has a wide range of applications in the medical industry and clinical treatment because of its anti-cancer, anti-oxidation, anti-coagulant, anti-HIV choleretic and hypolipidemic effects. Therefore, it is crucial to properly control the concentration of curcumin in food and medicine. In our work, a new and simple method for quantitative detection of curcumin was established by developing a “turn-off” fluorescence probe based on upconvert luminescent carbon quantum dots (p-CDs). The carbon quantum dots were synthesized with p-aminobenzoic acid (PABA) and ethanol by solvothermal method and have specific up-conversion luminescence properties which could be applied in other sensing field. In this sensor, the sensing mechanism of this fluorescent probe was based on the internal filter effect (IFE) between curcumin and p-CDs, the increasing in the concentration of curcumin causes the selective fluorescence quenching of p-CDs. Under optimum conditions, the fluorescence quenching intensity of p-CDs has a good liner relationship with curcumin in the range of 0.4-45 μΜ and with a detection limit of 0.133 μM. What's more, the fluorescent “turn-off” probe constructed with p-CDs exhibited high accuracy and recovery in the analysis of actual sample curry powder, demonstrating the fluorescence “turn-off” probe has potential application for the detection of curcumin in the complex matrixes.

Introduction Melatonin (MT), as an efferent hormonal signal of the circadian clock, is an indoleamine neuroendocrine hormone synthesized and secreted principally by the pineal gland at night under normal environmental conditions [1]. Melatonin exerts various physiological functions by binding to melatonin receptors, including regulating day and night rhythms, inhibiting tumor development, and regulating immunity [2]. In present work, we prepared an electrochemical sensor that can quickly detect melatonin and further studied the its electrooxidation behavior and reaction mechanism. This sensor is based on carbon nanofibers with FeCo bimetallic alloy dispersed and embedded in (FeCo@CNFs) by electrospinning and a thermal treatment process. Through the analysis and comparison of various characterization methods, it can be proved that the combination of bimetal and CNF can improve the electrochemical properties of the composites. We also analyzed the electrochemical behavior of melatonin at the FeCo@CNFs electrode. Compared with previous reports on melatonin detection, this sensor has a lower detection limit and a wider detection range. Characterization of FeCo@CNFs In Fig. 1A, the SEM image FeCo@CNFs have a homogeneous fiber structure with a diameter of approximately 100~200 nm. And it can be seen from its HRTEM images that the FeCo@CNFs are porous structure and decorated with nanoparticles (Fig. 1B). Moreover, it can be seen from Fig. 1C that the obvious lattice fringes are 0.19 nm and 0.33 nm, corresponding to (110) crystalline facet of FeCo alloy and (002) crystalline facet of graphitized carbon layer respectively, indicating that FeCo is wrapped by graphitized carbon fibers. It is well known that transition metals such as Fe and Co can not only promote the transformation of adjacent amorphous carbon to graphitized carbon, but also change the electron interaction between host and guest, reduce the local work function of carbon layer and promote the electrocatalytic reaction[3]. Results and Conclusions Fig. 1D shows the I-T curve of detection of MT in the stirring PB solution (pH 5.0) at FeCo@CNFs/GCE with the concentration ranging from 0.08μM to 400μM. It can be seen that the current response increases linearly with the increase of MT. The current response increased linearly with successive addition of MT and the linear relationship is Ip (μA) = 0.537 + 0.038C (μM) (R = 0.997) (Fig. 1E). The detection limit is estimated to be 2.7×10-9 mol L-1 (S/N=3). References [1] B. Claustrat, J. Brun, G. Chazot, The basic physiology and pathophysiology of melatonin, Sleep medicine reviews, 9 (2005) 11-24. [2] A. Lerchl, S. Schlatt, Influence of Photoperiod on Pineal Melatonin Synthesis, Fur Color, Body Weight, and Reproductive Function in the Female Djungarian Hamster, Phodopus sungorus, Neuroendocrinology, 57 (1993) 359-364. [3] X. Zou, X. Huang, A. Goswami, R. Silva, B.R. Sathe, E. Mikmekova, T. Asefa, Cobalt-embedded nitrogen-rich carbon nanotubes efficiently catalyze hydrogen evolution reaction at all pH values, Angewandte Chemie, 53 (2014) 4372-4376. Figure 1

A facile and highly sensitive electrochemical sensor for salidroside was fabricated based on multilayer ultrathin films (UTFs) containing Ni-Al layered double hydroxide (LDH) and carbon fibers that obtained by electrospinning technology. The X-ray diffraction (XRD), scanning electron microscope (SEM) and transmission electron microscopy (TEM) images show that the film surface is synthesized successfully. In addition, we constructed the electrochemical sensor using the composite nanomaterials we prepared to achieve detection of salidroside and this sensor showed a good linear range (0.2-120 mu M) and a low detection limit (0.067 mu M). It has also been successfully applied to the detection of actual samples, compared with HPLC method, satisfactory recovery rates have also been obtained.

This work demonstrates fabrication and performance (towards ofloxacin (OFL) detection) of a unique electrochemical sensor, composed of p-aminobenzene sulfonic acid (ASBA) and grapheme (GR). For this purpose, a glassy carbon electrode (GCE) was coated by GR using electrochemical deposition and then electro-polymerized by ABSA. The surface and morphology of the resulting composite pABSA/GR/GCE were analyzed using scanning electron microscopy. Oxidation peak currents obtained from the differential pulse voltammograms with the assistance of the composite pASBA/GR/GCE showed linear correlation to the OFL concentrations in the 0.1-40 mu mol/L range with the detection limits of acetaminophen is 0.03 mu mol/L (S/N = 3). We also demonstrated OFL detection using pASBA/GR/GCE in pharmaceutical formulations. These results indicate that pASBA/GR/GCE has very strong potential as an electro-analytical sensor for the detection of components in pharmaceutical formulations.

The sensitive determination of VB2 has broad analytical applications. In this work, a novel VB2 electrochemical sensor based on hydrothermal method was constructed to uniformly grow molybdenum disulfide and silver nanoparticles on the surface of electrospun carbon fiber. MoS2-Ag-CNF was characterized by scanning electron microscope, EDS spectrum, cyclic voltammetry, differential pulse voltammetry and electrochemical impedance spectroscopy. The sensor exhibited a high sensitivity of 0.05 μΜ to 40 μΜ with a fast response time and a low detection limit of 0.02 μM. The electrode also showed outstanding selectivity toward various interferences. These results indicate that the MoS2-Ag-CNF nanocomposites may be promising electrode materials for electrochemical biosensing.

In this work, we integrated the superiority of good conductivity, large surface area of carbon fibers and the catalytic property, good biocompatibility of polymer sulfosalicylic acid to construct a novel electrochemical sensor to detect theophylline in drug analysis. The morphology of nanocomposite was characterized by scanning electron microscopy (SEM). The polymerization between monomers was observed by Fourier transform infrared spectroscopy (FTIR). The composite between carbon material and polymer was verified by Raman spectrum. Under the optimal experimental conditions, the concentration of theophylline (0.6∼137 μM) and the peak current value revealed a good linear relationship and the limit of detection as low as 0.2 μM. In addition, the proposed sensor exhibits repeatability, stability and ease of selectivity.

Fluorescent pH probes are promising for both in vitro and in vivo pH detections in chemical and biochemical systems. Previously, the multi-color and whole cell pH sensing is a challenge for conventional fluorescent nanomaterials. In this work, we report an N, S co-doped carbon dots (N, S-CDs)-based fluorescent pH probe that can response to different incident light with tunable wavelength. The emission wavelength is tunable and correlated to the excitation wavelength, enabling self-adaptive multi-color sensing. The N, S-CDs was synthesized by a one-step hydrothermal method utilizing glucose, ammonium persulfate and ethylenediamine as precursors. The fluorescence of N, S-CDs shows a good linear relationship against pH values from 3.0 to 10.0 with a linear correlation coefficient of 0.996. The good biocompatibility and small size fulfill the demand of whole cell intracellular imaging. We have demonstrated that the N, S-CDs have successfully applied in HepG2 cells for the self-adaptive multi-color imaging.

基于石墨烯纳米材料和循环伏安法技术制备了聚对氨基苯磺酸/石墨烯修饰电极并研究了氧氟沙星(OFL)在该修饰电极上的电化学行为,建立了一种简单快速灵敏测定氧氟沙星的电化学分析方法.结果表明,与玻碳电极相比,对氨基苯磺酸/石墨烯电化学修饰电极能显著提高氧氟沙星的峰电流.在优化条件下,其检测线性范围为1～600μmol/L,最低检测限为(S/N=3)0.33μmol/L.该修饰电极具有较好的重现性和稳定性,用于实际样品氧氟沙星滴眼液的测定,效果良好.

A non-enzymatic glucose electrochemical sensor based on carbon nanofiber coat with nickel-cobalt layered double hydroxide (CNF@ Ni-Co LDH) which was made by electrospinning techniques and chemical deposition. The morphology and structural behaviours of the CNF@ Ni-Co LDH were investigated by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (XPS). Meanwhile, the electrochemical performances of the nanocomposite modified glassy carbon electrode (GCE) was demonstrated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The presence of Ni-Co LDH nanosheets on CNFs strongly improved the surface area and that thus enhanced its electrocatalysis efficiency. Meanwhile, the ratio of the Ni to Co was optimized to achieve the best electrocatalytic capability for glucose. The developed sensor exhibited a wide linear range (1-2000 mu M), low detection limit (0.03 mu M) and high sensitivity (1.47 mA mM(-1) cm(-2)) towards glucose. The excellent results demonstrated that the CNF@ Ni-Co LDH sensing platform might provide practical applicability and reliability towards human serum detection.