Nanomaterials-based immunosensors for avian influenza virus detection.

Avian influenza viruses (AIV) are capable of infecting a considerable proportion of the world's population each year, leading to severe epidemics with high rates of morbidity and mortality. The methods now used to diagnose influenza virus A include the Western blot test (WB), hemagglutination inhibition (HI), and enzyme-linked immunosorbent assays (ELISAs). But because of their labor-intensiveness, lengthy procedures, need for costly equipment, and inexperienced staff, these approaches are considered inappropriate. The present review elucidates the recent advancements in the field of avian influenza detection through the utilization of nanomaterials-based immunosensors between 2014 and 2024. The classification of detection techniques has been taken into account to provide a comprehensive overview of the literature. The review encompasses a detailed illustration of the commonly employed detection mechanisms in immunosensors, namely, colorimetry, fluorescence assay, surface plasmon resonance (SPR), surface-enhanced Raman spectroscopy (SERS), electrochemical detection, quartz crystal microbalance (QCM) piezoelectric, and field-effect transistor (FET). Furthermore, the challenges and future prospects for the immunosensors have been deliberated upon. The present review aims to enhance the understanding of immunosensors-based sensing platforms for virus detection and to stimulate the development of novel immunosensors by providing novel ideas and inspirations. Therefore, the aim of this paper is to provide an updated information about biosensors, as a recent detection technique of influenza with its details regarding the various types of biosensors, which can be used for this review.

Bioinorganic Synthesis of Sodium Polytungstate/Polyoxometalate in Microbial Kombucha Media for Precise Detection of Doxorubicin.

In this study, we have developed a new platform of polyoxometalate as a biocompatible and electrosensitive polymeric biosensor for the accurate detection of doxorubicin. For this purpose, we used a green synthesis approach using tartaric acid, glutamic acid, and kombucha solvent. Thanks to its bioinorganic components, the biogenic approach can chemically modify and improve the performance of the biosensor, which was experimentally confirmed. Our results showed excellent sensitivity (175.72 µA·µM-1·cm-2), low detection limit (DL, 8.12 nM), and low quantification limit (QL, 0.056 µM) when the newly developed biosensor was used. The results also show that the biosynthesized biosensor has improved performance in detecting DOX in the biological fluid with an accuracy of more than 99% depending on the components used, which underlines the high efficiency of the biosensor produced. Considering the body's physiological condition, the biosensor fabricated as a biocompatible component can show high efficiency. Therefore, its applicability for clinical use still needs to be studied in detail.

Hybrid of sodium polytungstate polyoxometalate supported by the green substrate for photocatalytic degradation of auramine-O dye.

Nowadays, textile industries have severely polluted the ecosystem and water sources via disposal of highly thermo- and photo-stable dyes within the ecology that require practical strategies to remove them from nature. In studies, the photocatalytic disinfection technique has been shown to have widespread applications in indoor air, environmental health, detection, biological, biomedical, laboratory hospital, pharmaceutical food industry, plant safety, waste water, effluents disposal, and drinking water disinfection. Herein, the sodium polytungstate (SPT) polyoxometalate (POM) was synthesized through a multi-step production procedure and hence modified via employing a green protocol by using tartaric acid, glutamic acid, and kombucha solvent toward efficient and total complete removal of the highly toxic, stable, and carcinogenic auramine-O (AO) dye from aqueous media. In this regard, developed materials were well-characterized, and their photocatalysis performance for photodegradation of AO dye was examined. Achieved results showed that the optimum absorption conditions were achieved at pH of 5.0, 15 mg/L of AO concentration, 0.04 g of photocatalyst dosage, and 110 min irradiation time, where SPT and modified SPT via green protocol showed full desirability (desirability function (DF) index of 1) along with 71.75 and 100% removal percentage, respectively. Obtained results justified the superior photocatalytic role of the SPT POM and its derived nanocluster that can be used for the complete removal of highly stable dyes from aqueous media till reaching the drinking water standard.

Bioactive Graphene Quantum Dots Based Polymer Composite for Biomedical Applications.

Today, nanomedicine seeks to develop new polymer composites to overcome current problems in diagnosing and treating common diseases, especially cancer. To achieve this goal, research on polymer composites has expanded so that, in recent years, interdisciplinary collaborations between scientists have been expanding day by day. The synthesis and applications of bioactive GQD-based polymer composites have been investigated in medicine and biomedicine. Bioactive GQD-based polymer composites have a special role as drug delivery carriers. Bioactive GQDs are one of the newcomers to the list of carbon-based nanomaterials. In addition, the antibacterial and anti-diabetic potentials of bioactive GQDs are already known. Due to their highly specific surface properties, π-π aggregation, and hydrophobic interactions, bioactive GQD-based polymer composites have a high drug loading capacity, and, in case of proper correction, can be used as an excellent option for the release of anticancer drugs, gene carriers, biosensors, bioimaging, antibacterial applications, cell culture, and tissue engineering. In this paper, we summarize recent advances in using bioactive GQD-based polymer composites in drug delivery, gene delivery, thermal therapy, thermodynamic therapy, bioimaging, tissue engineering, bioactive GQD synthesis, and GQD green resuscitation, in addition to examining GQD-based polymer composites.

Shape-controlled synthesis of zinc nanostructures mediating macromolecules for biomedical applications.

Zinc nanostructures (ZnONSs) have attracted much attention due to their morphological, physicochemical, and electrical properties, which were entailed for various biomedical applications such as cancer and diabetes treatment, anti-inflammatory activity, drug delivery. ZnONS play an important role in inducing cellular apoptosis, triggering excess reactive oxygen species (ROS) production, and releasing zinc ions due to their inherent nature and specific shape. Therefore, several new synthetic organometallic method has been developed to prepare ZnO crystalline nanostructures with controlled size and shape. Zinc oxide nanostructures' crystal size and shape can be controlled by simply changing the physical synthesis condition such as microwave irradiation time, reaction temperature, and TEA concentration at reflux. Physicochemical properties which are determined by the shape and size of ZnO nanostructures, directly affect their biological applications. These nanostructures can decompose the cell membrane and accumulate in the cytoplasm, which leads to apoptosis or cell death. In this study, we reviewed the various synthesis methods which affect the nano shapes of zinc particles, and physicochemical properties of zinc nanostructures that determined the shape of zinc nanomaterials. Also, we mentioned some macromolecules that controlled their physicochemical properties in a green and biological approaches. In addition, we present the recent progress of ZnONSs in the biomedical fields, which will help centralize biomedical fields and assist their future research development.

Differentiable detection of ethanol/methanol in biological fluids using prompt graphene-based electrochemical nanosensor coupled with catalytic complex of nickel oxide/8-hydroxyquinoline.

Serious health hazards of volatile organic compounds such as methanol and ethanol for living species and their adverse effects on the environment raised a global requirement for developing a portable, precise, and sensitive detection platform capable of simultaneous and differentiable detection of alcohols in aquatic biological and non-biological fluids. Each year, methanol toxicity causes serious healthcare problems and leads to high mortalities in developing countries. Hence, designing and developing a practical nanosensor for diagnostic applications and environmental monitoring is crucial. Herein, we have addressed this demand by fabricating a portable, ultra-sensitive, and precise nanosensor capable of simultaneous and differentiable detection of methanol and ethanol in any aquatic specimen in about 1 min. The nanosensor is composed of the integrated graphene oxide (GO) flakes with the catalytic complex of NiOx and 8-hydroxyquinoline (8HQ) capable of identification of methanol and ethanol with an analytical sensitivity/detection limit of 30.66 µA(µmol/mL)-1.cm-2/6.87 nmol mL-1 and 118.99 µA(µmol/mL)-1.cm-2/1.80 nmol mL-1 using voltammetric assays between the linear range of 0.014-0.01 µmol mL-1 and 0.83-0.58 µmol mL-1, respectively. The outcome of the assessments exhibited the favorable capability of the prepared nanosensor for precise/prompt detection of alcohols in blood specimens and showed an ideal correlation with the outcome of the gold standard.

Antibody mounting capability of 1D/2D carbonaceous nanomaterials toward rapid-specific detection of SARS-CoV-2.

Carbonaceous immunosensors are ideal nanoplatforms for developing rapid, precise, and ultra-specific diagnostic kits capable of early detection of viral infectious illnesses such as COVID-19. However, developing a proper carbonic immunosensor requires stepwise protocols to find optimum operating conditions to minimize drawbacks. Herein, for the first time and through a stepwise protocol, activation, and monoclonal IgG antibody mounting capability of multi-walled carbon nanotubes (MWCNTs) at two diverse outer diameters (ODs), viz., 20-30 nm and 50-80 nm, and graphene deriv atives (graphene oxide (GO) and reduced graphene oxide (rGO)) were examined and compared with each other toward finding the prime carbonaceous nanomaterial(s) for maximized antibody loading efficiency along with an ideal detection limit (DL) and sensitivity. Next, the effect of common amplifying agents, i.e., Au nanostars (Au NSs) and Ag nanowires (Ag NWs), on the total performance of the best carbonaceous structure was carefully assessed, and the responsible detection mechanism is investigated in detail. Next, the developed carbonaceous immunosensors were assessed via voltammetric and impedance assays, and their performances toward specific detection of SARS-CoV-2 antigen through immunoreaction were examined in detail. The study's outcome showed the superior performance of conjugated rGO-based immunosensor with Au NSs toward specific and quick (1 min) detection of SARS-CoV-2 antigen in biological fluids compared with other 1D/2D carbonaceous nanomaterials.

Graphene-Based Femtogram-Level Sensitive Molecularly Imprinted Polymer of SARS-CoV-2.

Rapid distribution of viral-induced diseases and weaknesses of common diagnostic platforms for accurate and sensitive identification of infected people raises an urgent demand for the design and fabrication of biosensors capable of early detection of viral biomarkers with high specificity. Accordingly, molecularly imprinted polymers (MIPs) as artificial antibodies prove to be an ideal preliminary detection platform for specific identification of target templates, with superior sensitivity and detection limit (DL). MIPs detect the target template with the "lock and key" mechanism, the same as natural monoclonal antibodies, and present ideal stability at ambient temperature, which improves their practicality for real applications. Herein, a 2D MIP platform consisting of decorated graphene oxide with the interconnected complex of polypyrrole-boronic acid is developed that can detect the trace of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen in aquatic biological samples with ultrahigh sensitivity/specificity with DL of 0.326 and 11.32 fg mL-1 using voltammetric and amperometric assays, respectively. Additionally, the developed MIP shows remarkable stability, selectivity, and accuracy toward detecting the target template, which paves the way for developing ultraspecific and prompt screening diagnostic configurations capable of detecting the antigen in 1 min or 20 s using voltammetric or amperometric techniques.

Renewable Carbon Nanomaterials: Novel Resources for Dental Tissue Engineering.

Dental tissue engineering (TE) is undergoing significant modifications in dental treatments. TE is based on a triad of stem cells, signaling molecules, and scaffolds that must be understood and calibrated with particular attention to specific dental sectors. Renewable and eco-friendly carbon-based nanomaterials (CBMs), including graphene (G), graphene oxide (GO), reduced graphene oxide (rGO), graphene quantum dots (GQD), carbon nanotube (CNT), MXenes and carbide, have extraordinary physical, chemical, and biological properties. In addition to having high surface area and mechanical strength, CBMs have greatly influenced dental and biomedical applications. The current study aims to explore the application of CBMs for dental tissue engineering. CBMs are generally shown to have remarkable properties, due to various functional groups that make them ideal materials for biomedical applications, such as dental tissue engineering.

Bioinorganic Synthesis of Polyrhodanine Stabilized Fe3O4/Graphene Oxide in Microbial Supernatant Media for Anticancer and Antibacterial Applications.

Polyrhodanines have been broadly utilized in diverse fields due to their attractive features. The effect of polyrhodanine- (PR-) based materials on human cells can be considered a controversial matter, while many contradictions exist. In this study, we focused on the synthesis of polyrhodanine/Fe3O4 modified by graphene oxide and the effect of kombucha (Ko) supernatant on results. The general structure of synthetic compounds was determined in detail through Fourier-transform infrared spectroscopy (FT-IR). Also, obtained compounds were morphologically, magnetically, and chemically characterized using scanning electron microscopy (SEM) and vibrating sample magnetometer (VSM), energy dispersive X-ray (EDX) analysis. The antibacterial effects of all synthesized nanomaterials were done according to CLSI against four infamous pathogens. Also, the cytotoxic effects of the synthesized compounds on the human liver cancer cell line (Hep-G2) were assessed by MTT assay. Our results showed that Go/Fe has the highest average inhibitory effect against Escherichia coli and Pseudomonas aeruginosa, and this compound possesses the least antimicrobial effect on Staphylococcus aureus. Considering the viability percent of cells in the PR/GO/Fe3O4 compound and comparing it with GO/Fe3O4, it can be understood that the toxic effects of polyrhodanine can diminish the metabolic activity of cells at higher concentrations (mostly more than 50 µg/mL), and PR/Fe3O4/Ko exhibited some promotive effects on cell growth, which enhanced the viability percent to more than 100%. Similarly, the cell viability percent of PR/GO/Fe3O4/KO compared to PR/GO/Fe3O4 is much higher, which can be attributed to the presence of kombucha in the compound. Consequently, based on the results, it can be concluded that this novel polyrhodanine-based nanocompound can act as drug carriers due to their low toxic effects and may open a new window on the antibacterial agents.

Recent Advancements in Polythiophene-Based Materials and their Biomedical, Geno Sensor and DNA Detection.

In this review, the unique properties of intrinsically conducting polymer (ICP) in biomedical engineering fields are summarized. Polythiophene and its valuable derivatives are known as potent materials that can broadly be applied in biosensors, DNA, and gene delivery applications. Moreover, this material plays a basic role in curing and promoting anti-HIV drugs. Some of the thiophene's derivatives were chosen for different experiments and investigations to study their behavior and effects while binding with different materials and establishing new compounds. Many methods were considered for electrode coating and the conversion of thiophene to different monomers to improve their functions and to use them for a new generation of novel medical usages. It is believed that polythiophenes and their derivatives can be used in the future as a substitute for many old-fashioned ways of creating chemical biosensors polymeric materials and also drugs with lower side effects yet having a more effective response. It can be noted that syncing biochemistry with biomedical engineering will lead to a new generation of science, especially one that involves high-efficiency polymers. Therefore, since polythiophene can be customized with many derivatives, some of the novel combinations are covered in this review.

Ultra-precise label-free nanosensor based on integrated graphene with Au nanostars toward direct detection of IgG antibodies of SARS-CoV-2 in blood.

Rapid distribution of airborne contagious pathogenic viruses such as SRAS-CoV-2 and their severely adverse impacts on different aspects of the human society, along with significant weaknesses of traditional diagnostic platforms, raised the global requirement for the design/fabrication of precise, sensitive, and rapid nanosystems capable of specific detection of viral illnesses with almost negligible false-negative results. To address this indispensable requirement, we have developed an ultra-precise fast diagnostic platform capable of detecting the trace of monoclonal IgG antibody against S1 protein of SARS-CoV-2 within infected patients' blood specimens with COVID-19 in about 1 min. The as-developed electrochemical-based nanosensor consists of a highly activated graphene-based platform in conjunction with Au nanostars, which can detect SARS-CoV-2 antibodies with a fantastic detection limit (DL) and sensitivity of 0.18 × 10-19%V/V and 2.14 µA.%V/V.cm-2, respectively, in human blood plasma specimens even upon the presence of a high amount of interfering compound/antibodies. The nanosensor also exhibited remarkable sensitivity/specificity compared with the gold standard (i.e., ELISA assay), which furtherly confirmed its superb performance.

Ultra-sensitive viral glycoprotein detection NanoSystem toward accurate tracing SARS-CoV-2 in biological/non-biological media.

Rapid person-to-person transfer of viruses such as SARS-CoV-2 and their occasional mutations owing to the human activity and climate/ecological changes by the mankind led to creation of wrecking worldwide challenges. Such fast transferable pathogens requiring practical diagnostic setups to control their transfer chain and stop sever outbreaks in early stages of their appearance. Herein, we have addressed this urgent demand by designing a rapid electrochemical diagnostic kit composed of fixed/screen printed electrodes that can detect pathogenic viruses such as SARS-CoV-2 and/or animal viruses through the differentiable fingerprint of their viral glycoproteins at different voltage positions. The working electrode of developed sensor is activated upon coating a layer of coupled graphene oxide (GO) with sensitive chemical compounds along with gold nanostars (Au NS) that can detect the trace of viruses in any aquatic biological media (e.g., blood, saliva and oropharyngeal/nasopharyngeal swab) through interaction with active functional groups of their glycoproteins. The method do not require any extraction and/or biomarkers for detection of target viruses and can identify trace of different pathogenic viruses in about 1 min. The nanosensor also demonstrated superior limit of detection (LOD) and sensitivity of 1.68 × 10-22 µg mL-1 and 0.0048 µAµg.mL-1. cm-2, respectively, toward detection of SARS-CoV-2 in biological media, while blind clinical evaluations of 100 suspected samples furtherly confirmed the superior sensitivity/specificity of developed nanosystem toward rapid identification of ill people even at incubation and prodromal periods of illness.

Recent Progress in Chemical Composition, Production, and Pharmaceutical Effects of Kombucha Beverage: A Complementary and Alternative Medicine.

Kombucha is a valuable traditional natural tea that contains beneficial compounds like organic acids, minerals, different vitamins, proteins, polyphenols, and several anions. Kombucha possesses anticancer, antioxidant, antimicrobial, and antifungal activity as well as hepatoprotective effects. Considering the unique properties of Kombucha, several investigations have already been conducted on its nutritional properties. In this review, an effort has been devoted to pool recent literature on the biomedical application of Kombucha under the objectives, including the chemical composition of Kombucha and industrial production, and highlight different properties of Kombucha. Finally, we explain its adverse effects and prospect. This review is an active, in-depth, and inclusive report about Kombucha and its health benefits.

Rapid ultrasound-assisted microextraction of atorvastatin in the sample of blood plasma by nickel metal organic modified with alumina nanoparticles.

In the present work, nickel-1,4-benzenedioxyacetic acid was synthesized as a rod-like metal organic material and then modified with alumina nanoparticles to synthesize nickel metal organic modified-Al2 O3 nanoparticles. The material was found as an efficient sorbent for the enrichment of atorvastatin in human blood plasma. After the extraction of the sample of plasma by ultrasound-assisted dispersive solid phase extraction, high performance liquid chromatography-ultraviolet was used to determine the quantitatively pre-concentrated interest analyte. The conditions for optimum extraction were achieved by the optimization of the volume of eluent, dosage of the sorbent, and time of sonication. Solution pH of 7.0, 250 µL of ethanol, 45 mg of the sorbent, and 10 min of sonication time were the conditions for extracting the atorvastatin maximum recovery of higher than 97.0%. By using desirability function for the optimization of the process, the present method showed a response that was linear ranging from 0.2 to 800 ng/mL with regression coefficient of 0.999 in the plasma of human blood with a satisfactory detection limit of 0.05 ng/mL, while the precision of interday for the current method was found to be <5%. It can be concluded that dispersive solid phase extraction method is effective for the extraction of atorvastatin from human plasma samples (97.4-102%) due to its easy operation, simplicity, repeatability, and reliability.

Superior X-ray Radiation Shielding Effectiveness of Biocompatible Polyaniline Reinforced with Hybrid Graphene Oxide-Iron Tungsten Nitride Flakes.

X-ray radiation is a harmful carcinogenic electromagnetic source that can adversely affect the health of living species and deteriorate the DNA of cells, thus it's vital to protect vulnerable sources from them. To address this flaw, the conductive polymeric structure of polyaniline (PANi) was reinforced with diverse filler loadings (i.e., 25 wt % and 50 wt %) of hybrid graphene oxide-iron tungsten nitride (ITN) flakes toward attenuation of X-ray beams and inhabitation of microorganisms' growth. Primary characterizations confirmed the successful decoration of graphene oxide (GO) with interconnected and highly dense structure of iron tungsten nitride with a density of about 24.21 g.cm⁻3 and reinforcement of PANi with GO-ITN. Additionally, the outcome of evaluations showed the superior performance of developed shields, where a shield with 1.2 mm thickness containing 50 wt % GO-ITN showed 131.73 % increase in the electrical conductivity (compared with neat PANi) along with 78.07%, 57.12%, and 44.99% decrease in the amplitude of the total irradiated X-ray waves at 30, 40, and 60 kVp tube voltages, respectively, compared with control X-ray dosage. More importantly, the developed shields not only showed non-toxic nature and improved the viability of cells, but also completely removed the selected microorganisms at a concentration of 1000 µg.mL-1.

Picomolar-level detection of mercury within non-biological/biological aqueous media using ultra-sensitive polyaniline-Fe3O4-silver diethyldithiocarbamate nanostructure.

Mercury as the 3rd most toxic, non-biodegradable, and carcinogenic pollutant can adversely affect the ecosystem and health of living species through its bioaccumulation within the nature that can affect the top consumer in the food chain; therefore, it is vital to sense/remove Hg2+ within/from aqueous media using practical approaches. To address this matter, we modified the glassy carbon electrode (GCE) with ultra-sensitive, interconnected, sulfurized, and porous nanostructure consisted of polyaniline-Fe3O4-silver diethyldithiocarbamate (PANi-F-S) to enhance the sensitivity, selectivity, and limit of detection (LOD) of the sensor. Obtained results showed that at optimum conditions (i.e., pH value of 7, deposition potential of - 0.8 V, and accumulation time of 120 s), for Hg2+ concentration ranging from 0.4 to 60 nM, the modified electrode showing linear relative coefficient of 0.9983, LOD of 0.051 nM, LOQ of 0.14 nM, and sensitivity of 1618.86 µA µM-1 cm-2 highlights superior sensitivity of the developed platform until picomolar level. Additionally, the modified electrode showed ideal repeatability, stability, reproducibility, and selectivity (by considering Zn2+, Cd2+ Pb2+, Cu2+, Ni2+, and Co2+ as metal interferences) and recovered more than 99% of the Hg2+ ions within non-biological (mineral, tap, and industrial waters) and biological (blood plasma sample) fluids. Graphical abstract.

Coupled graphene oxide with hybrid metallic nanoparticles as potential electrochemical biosensors for precise detection of ascorbic acid within blood.

Ascorbic acid (AA) as an essential biological molecule for proper performance of body can act as a biological metric for precise detection of various kinds of disease through measuring the level of oxidative stress; thus its precise/dividable detection is an urgent requirement for development of advanced biosensors. To address this requirement, we decorated well-exfoliated graphene oxide (GO) with Ag and hybrid Ag-Fe3O4 metallic nanoparticles toward precise, real-time and repeatable detection of AA within the blood plasma samples via electrochemical approaches that led to the development of a retrievable biosensor. Outcome of performed evaluations showed that modification of glassy carbon electrode (GCE) with selected additives significantly improved its sensitivity/selectivity. In this matter, the modified GCE with GO-Ag-Fe3O4 showed limit of detection and sensitivity of 74 nM and 1146.8 µA mM-1 cm-2, respectively, within the concentration range of 0.2-60 µM. Additionally, the modified electrode kept 91.23% of its total performance after 15 days of performance and detected the oxidation peak of AA even with present of 50 fold of annoying contents which highlighting its superior stability/selectivity. More importantly, the developed electrode showed recovery range between 96.0 and 104.4% within the human blood plasma samples that confirmed the ideal capability of developed platform for accurate detection of AA within biological fluids.

Data on cytotoxic and antibacterial activity of synthesized Fe3O4 nanoparticles using Malva sylvestris.

The biosynthesis of materials using medicinal plants can be a low-cost and eco-friendly approach due to their extraordinary properties. Herein, we reported a facile synthesis of Fe3O4 nanoparticles using Malva sylvestris. The surface morphology, functional groups, and elemental analysis were done to characterize the synthesized nanoparticles. The cytotoxicity performance of the synthesized nanoparticles was analyzed by exposing nanoparticles to MCF-7 and Hep-G2 cancer cell lines through MTT colorimetric assay and the IC50 value was defined as 100 µg/mL and 200 µg/mL, respectively. The antibacterial performance of synthesized nanoparticles against four different bacterial strains including Staphylococcus aureus, Corynebacterium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were assessed through microdilution broth method. The synthesized Fe3O4 nanoparticles using Malva sylvestris demonstrated higher antibacterial effects against Gram-positive strains with MIC values of 62.5 µg/mL and 125 µg/mL which increase the inhibitory percentage to more than 90%.

Construction of molecularly imprinted nanoparticles by employing ultrasound waves for selective determination of doxepin from human plasma samples: Modeling and optimization.

In this work, molecularly imprinted nanoparticles (MINPs) were applied as selective adsorbent for ultrasound-assisted micro-solid-phase extraction (UAMSPE) of doxepin (DP) from human plasma samples, which was then cleaned up, pre-concentrated and subjected to HPLC. The MINPs were synthesized based on a non-covalent approach by precipitation polymerization utilizing methacrylic acid and styrene as functional monomers, DP as template, ethylene glycol dimethacrylate as cross-linker and 2,2-azobisisobutyronitrile (AIBN) as initiator. The obtained MINPs were characterized by Fourier transform-infrared and field emission scanning electron microscopy. Factors influencing the efficiency of UAMSPE such as sonication time, volume of eluent solvent and amount of sorbent were investigated using a central composite design and the optimal points were identified as 4 min of sonication time, 380 µL of eluent solvent and 30 mg of sorbent. Under optimized conditions, the proposed method has linear responses in the range of 0.2-2000 ng mL-1 , with a satisfactory limit of detection of 0.04 ng mL-1 and limit of quantification of 0.11 ng mL-1 .