Systematic Experimental Design Research Articles

Physical Origin of the Ferroelectric-Type Hysteresis in MIM Structures with Amorphous Dielectric Film.

The ferroelectric-type characteristics in metal-insulator-metal (MIM) structures with amorphous dielectrics are observed, which may open a new window for a class of new ferroelectric devices. However, the working principles of these ferroelectric devices are not well explained. It has been proposed that oxygen ion (O2-) and charged vacancy (Vo2+) migrations are associated with this ferroelectric-like behavior. In this work, a systematic experimental design is carried out to investigate the origin of O2- and Vo2+ (from the interface or bulk oxide?), the transport species (O2-, Vo2+, or both of these two species?), and the ion transport mode (long-range transport or local movement?). The experimental results answered all these questions. In addition, the role of the thickness of the dielectrics is also studied. This work sets the fundamentals of these amorphous oxide-based devices, guiding future explorations to engineer them.

Analysis of Erosion of Surfaces in Falling Particle Concentrating Solar Power

Abstract Next generation concentrating solar power (CSP) systems, which utilize solid particles for energy capture, transport, and storage, offer prospects for higher temperature operation, improved efficiency, and reduced overall costs. Nevertheless, the continuous impingement of particles on component materials can result in substantial erosion, significantly constraining the performance and longevity of the components. A comprehensive understanding of particle erosion on surfaces is essential for designing components and operational parameters or coatings that minimize wear. This study presents a computational physics-based particle tracking model of the erosion rate of incident surfaces under different geometric, operational, and particle parameters. The computational model is validated with experimental measurements conducted as part of the study. Computational simulations are presented to elucidate the effects of each parameter and further used to investigate erosion rates in a systematic design of experiments covering a wide range of parameters. Based on the simulation results, a generalized analytical model is developed to relate erosion wear to pertinent dimensionless groups governing the physics of the process. The analytical model is shown to be accurate to within 10% and its use in understanding surface erosion as well as designing wear-resistant coatings to limit erosion within acceptable values is presented.

(Ga1-xAlx)4B2O9: controlled surface acid-base properties and catalytic behavior towards the Strecker reaction.

Solid bases are valuable catalysts for industrial syntheses. However, controlling the basicity of these catalysts remains a challenge. Ga4B2O9, due to μ3-O within its structure, could behave as a special solid base catalyst exhibiting intrinsic Lewis basicity. In this work, a sol-gel method was proposed to obtain continuously adjustable acidity and basicity of the metal borate catalyst (AlxGa1-x)4B2O9. According to the results of NH3-TPD, CO2-TPD, and the systematic experimental design, Lewis basic sites originating from GaO5 groups in (AlxGa1-x)4B2O9 boost the Strecker reaction rather than the Lewis acid sites related to unsaturated Al. This work illustrates the possible application of bulk-type solid solutions with simultaneous Lewis acid and base sites for the first time. A reaction mechanism has also been proposed based on the catalytic reaction results.

Deciphering the degradation mechanisms of nano-Si and micro-SiO anodes in lithium-ion battery full-cells using distribution relaxation times analysis

Silicon (Si) and silicon monoxide (SiO) have attracted great interest as next-generation anode materials for lithium-ion batteries (LiBs) due to their high energy density. However, their commercialization has been hindered by rapid capacity fading, which stems from mechanical degradation (e.g., cracking and delamination) and the aggressive formation of solid electrolyte interphase (SEI) layer. While understanding these degradation mechanisms in batteries necessitates in-operando measurement techniques, very few non-destructive analytical methods have been documented in literature. This paper highlights the effectiveness of combined electrochemical impedance spectroscopy (EIS) and distribution of relaxation times (DRT) techniques in performing systematic characterization of LiNi0.6Mn0.2Co0.2O2 (NMC)/nano-Si and NMC/micro-SiO full-cells. The systematic design of experiments enabled the separate deconvolution of anode and cathode aging using symmetrical cells. This approach offered a clear understanding of the overall degradation mechanisms in the full-cells. The major impedance sources in the NMC/nano-Si full-cell were anode contact impedance, resulting from mechanical degradation of Si, and cathode charge transfer impedance, due to significant lithium loss and consequently deeper extraction of lithium ions in NMC. In contrast, micro-SiO anodes exhibited less electrode-level degradation, as evidenced by SEM images and relatively stable impedance behaviors during extended cycling, which strongly corroborate its superior capacity retention (66 % at 300th cycle) compared to that of nano-Si anode in full-cells (26.5 % at 300th cycle).

Selective Profiling of Carboxylic Acid in Crude Oil by Halogen Labeling Combined with Liquid Chromatography and High-Resolution Mass Spectrometry.

Carboxylic acids are a small but essential compound class within petroleum chemistry, influencing crude oil behaviors in production and processing and causing environmental impacts. Detailed structural information is fundamental to understanding their influence on petroleum characteristics. However, characterizing acids in crude oil remains challenging due to matrix effects, structural diversity, and low abundance. In this work, we present a new methodology for profiling carboxylic acids by liquid-liquid extraction and selective derivatization using 4-bromo-N-methylbenzylamine (4-BNMA) followed by liquid chromatography and electrospray ionization Orbitrap mass spectrometry (LC-ESI-Orbitrap MS). The fragmentation of 4-BNMA derivatives produces a unique product ion pair, m/z 169/171, enabling the identification of chromatographic fractions containing carboxylic acids. The mass spectra of the corresponding fractions are extracted, and the acids are further computationally isolated based on the isotopic pattern. The method was optimized and validated using acid standards and systematic experimental designs, assuring robustness and sensitivity for nontarget screening purposes. This method detected up to 380 carboxylic acids in six Danish North Sea crude oils, with up to two carboxyl and other heteroatom functionalities (NSO). The results indicated that the most populated species are fatty acids (double bond equivalent (DBE) = 1) and small aromatic acids (DBE = 2-6). The predominance and diversities of compound classes in different samples are consistent with their corresponding bulk properties. Polyfunctional acids (Ox, NxOx, and SxOx) were observed due to exposure to oxidation and biodegradation. Also, the approach's applicability benefits high-resolution MS analysis by simplifying data processing for crude oil and potentially other high-organic and aqueous samples.

High-speed waveguide lateral Ge/Si avalanche photodetector for C-band and L-band

Germanium/silicon (Ge/Si) avalanche photodiodes (APDs) have been intensively investigated and are widely used in various fields, such as near-infrared detection and quantum communication. However, existing research of Ge/Si APDs mostly focuses on a single optical communication band. The influence of wavelengths has not been studied. In this paper, we propose a lateral separate absorption multiplication (SAM) APD and conduct an in-depth research into the performance of Ge/Si APDs at different wavelengths. We reveal a significant enhancement in the performance of Ge/Si APDs at L-band (1600 nm) compared to the C-band (1550 nm). A gain-bandwidth product of 279 GHz corresponding to a gain of 18.4 and a bandwidth of 15.2 GHz are achieved at 1600 nm. Through systematic experimental design and theoretical analysis, we evaluate the mechanisms of the higher gain, providing insights into its potential applications in the field of optical communication. This study holds significant implications for expanding the application scope of Ge/Si APDs in optical communication, providing experimental support for their superior performance at higher wavelengths and potentially driving advancements in related technologies.

Powder-blown laser-based directed energy deposition of (14M) Ni-Mn-Ga magnetic shape memory alloy

Ni-Mn-Ga-based magnetic shape memory (MSM) alloys are renowned for their large magnetic-field-induced strains, making them attractive for compact magnetically controlled actuators requiring high response frequencies and large reversible deformations. In this study, Ni-Mn-Ga alloy samples were deposited using powder-blown laser-based directed energy deposition (DED-LB), employing gas-atomised powder pre-alloyed with excess Mn. The samples were deposited following a systematic experimental design, varying the applied laser power and employing two melting strategies: unidirectional and bidirectional. The results demonstrate the feasibility of achieving high relative densities (>97.5 %) in multi-layered Ni-Mn-Ga samples through DED-LB. All as-deposited samples exhibited a consistent 0.7–0.9 at% Mn loss in comparison to the powder feedstock, thus showing that the Mn overdosing requirements for DED-LB differ from those in laser powder bed fusion. Both as-deposited and heat-treated samples exhibited seven-layered modulated (14 M) martensite structures at ambient temperature. In contrast, the heat-treated samples also exhibited fully reversible martensite transformation at around 66 ºC and a Curie temperature at around 94 ºC. Distinct microstructural characteristics were observed based on the melting strategy, with bidirectional melting promoting the formation of large columnar grains with a strong <100> texture approximately along the build direction. This study highlights the potential of DED-LB processes in manufacturing relatively large (mm to cm scale) functional Ni-Mn-Ga actuators and contributes to the ongoing efforts in laser additive manufacturing of functional materials.

Cultivation of a naturally resilient Chlorella sp.: A bioenergetic strategy for valorization of cheese whey for high nutritional biomass production

This study investigated Chlorella's capacity to treat cheese whey (CW) effluent and produce a high-nutritional value biomass, by using a systematic sequential experimental design. Physicochemical analysis of CW revealed its high pollution load, characterized by elevated levels of lactose, phosphorus, and nitrogen, as well as high turbidity due to the presence of whey solids. Screening experiments demonstrated that trace mineral addition and continuous air supply are essential factors for Chlorella biomass production in CW (>800 mg·mL−1). Furthermore, whey solids did not hinder Chlorella growth, with notable biomass production observed even in undiluted CW, demonstrating this microalga's ability to adapt metabolically to the complex environment. Laboratory-scale photobioreactor experiments confirmed Chlorella's ability to produce biomass in CW, outperforming controls (>800 mg·mL−1). Bioremediation potential assessment exhibited significant reductions in organic pollutants (>14 g·L−1 COD), nitrogen (>400 mg·L−1), phosphorus (>140 mg·L−1) and sodium (>650 mg·L−1). CW solids were also removed with Chlorella harvesting (>99 %). Harvested algal biomass was enriched with proteins (>40 g·100 g−1), polyunsaturated fatty acids (>9 % TFA) and pigments, offering potential applications in nutraceutical and pharmaceutical industries. Overall, this study highlights Chlorella's efficacy in CW treatment and biomass valorization, offering a sustainable solution for dairy wastewater management while producing valuable resources.

Engineering zinc slurry anodes for high-performance primary alkaline batteries

The anode in Zn alkaline batteries is complex, comprised of zinc powder, gelled electrolyte, and additives, including surfactants. Optimizing the performance of these anodes means improving material utilization and suppressing corrosion of the electroactive zinc, which translates in real cells to higher energy density and longer shelf life. A challenge with optimizing these anodes has been in isolating the performance of the zinc slurry from the rest of the cell components in traditional, high-throughput cell-build studies. In this work, we use a combination of ex-situ and in-situ platforms to understand the effects of Zn content, KOH weight percent in the electrolyte, surfactant type and surfactant level on anode behavior. This is done by using electrochemical techniques including electrochemical impedance spectroscopy (EIS), linear polarization resistance (LPR), potentiodynamic polarization (PDP), and constant current (galvanostatic) discharge (CCD). The results of these experiments were combined with a systematic design of experiments (DoE) matrix, allowing for optimized slurries to be realized and tested in-situ in commercially representative cells. This work can aid in intelligently designing zinc slurries for deployment in commercial products.

The Impact of Food Waste Compost, Vermicompost, and Chemical Fertilizers on the Growth Measurement of Red Radish (Raphanus sativus): A Sustainability Perspective in the United Arab Emirates.

The pressing need for sustainable agricultural practices, especially with the increasing population, has directed attention towards alternative fertilizers that enhance crop yield while preserving soil integrity and reducing food loss. The current study investigated the comparative efficacy of food waste compost (FOWC), vermicompost, and chemical fertilizers on the growth of red radish. The present work used a systematic experimental design to evaluate plant growth parameters, including radish weight and height. The soil quality was determined by measuring the pH and electrical conductivity for all soil samples. The results indicated a significant variation in red radish fresh weight among different treatments. For example, the 25% vegetable and fruit waste compost (VFWC) treatment demonstrated a relatively high mean fresh weight, while the 50% mixed compost (MC) treatment yielded a much lower mean fresh weight. These numbers underscore the potential efficacy of specific food waste treatments in enhancing plant growth, with vermicompost at 50% and VFWC at 25% showing considerable promise in increasing crop yield. The current study concluded that FOWC and vermicompost significantly improved plant growth, advocating for their use as sustainable and environmentally friendly alternatives to chemical fertilizers. The current findings emphasized the importance of selecting appropriate fertilizer types and concentrations to optimize agricultural productivity and environmental sustainability, supporting the incorporation of food waste into agricultural systems as a beneficial resource.

Impact of probiotics, prebiotics, and synbiotics on digestive enzymes, oxidative stress, and antioxidant defense in fish farming: current insights and future perspectives

There has been a surge of research in the aquaculture industry investigating probiotic, prebiotic, and synbiotic interventions on the physiological mechanisms of fish, specifically digestive enzymes, oxidative stress, and antioxidant defense. In fish, probiotics have been shown to improve nutrient utilization and growth performance by stimulating digestive enzymes. Meanwhile, probiotics, prebiotics and synbiotics have also been studied for their ability to modulate oxidative stress and antioxidant defense mechanisms in fish, highlighting their multifaceted health benefits. This review identified current trends, research gaps, and future considerations in this evolving field. Although promising findings have been made, a significant research gap exists in understanding the specific role of probiotics prebiotics, and synbiotics in modulating digestive enzymes, oxidative stress, and antioxidant defense systems in a variety of fish species. As this study investigate into the existing body of literature, it becomes evident that while certain aspects of these interactions have been elucidated, a nuanced and comprehensive understanding still needs to be discovered. The variations in experimental design, species-specific responses, and the lack of standardized methodologies contribute to the complexity of the field. Digestive physiology and antioxidant defense mechanisms vary among different fish species, so future research should focus on species-specific responses to probiotic, prebiotic, and synbiotic formulations. It will also be possible to establish robust correlations between dietary interventions and observed effects through a systematic experimental design and methodology approach. Accordingly, further research is needed to understand the interactions between probiotics, prebiotics, and synbiotics in fish and digestive enzymes, oxidative stress, and antioxidant defense. Identifying research gaps and adopting standardized methodologies can help develop tailored strategies to optimize aquaculture fish health and growth performance.

FORMULATING AND CHARACTERIZING AN OIL-IN-WATER PALM OIL FREE FATTY ACID-BASED NANOEMULSIONS FOR CRUDE OIL EXTRACTION PERFORMANCE

Nanoemulsion is a promising medium for chemically enhanced oil recovery (cEOR) due to its ability to reduce interfacial tension and modify the wettability of reservoir rocks. This work focuses on formulating stable oil-in-water (O/W) nanoemulsions through high-energy ultrasonication method, with oleic acid as the primary component and is stabilized with a non-ionic Tween 40 surfactant in distilled water. Systematic experimental designs, employing response surface methodology (RSM), were implemented to develop polynomial models for various responses related to the dynamic and stability properties, and crude oil extraction performance. The p-value indicator (p-value &lt; 0.05) is utilized to assess the significance of the models and independent variables. Overall, the formulation for achieving the lowest surface tension involves 0.41 wt.% oleic acid mixed with 0.81 wt.% Tween 40 at 60 °C. Meanwhile, the highest viscosity attained with 1.0 wt.% oleic acid mixed with 1.0 wt.% Tween 40 at 30 °C. For stable nanoemulsion, the best conditions are 1.69 wt.% oleic acid, sonicated for 15 minutes at 25 °C. Additionally, an optimal condition for effective crude oil extraction is at nanoemulsion preparation with sonication time of 15 minutes and contact time of 12 hours in the immersion experiment. To this end, this work contributes valuable insights into the formulation and characterization of stable oleic acid O/W nanoemulsions for potential EOR applications. The findings enhance understanding of nanoemulsion properties and their potential as effective agents in crude oil recovery.

Free radicals trigger the closure of open pores in lignin-derived hard carbons toward improved sodium-storage capacity

The chemical activation of various precursors is effective for creating additional closed pores in hard carbons for sodium storage. However, the formation mechanism of closed pores under the influence of pore-forming agents is not well understood. Herein, an effective chemical activation followed by a high-temperature self-healing strategy is employed to generate interconnected closed pores in lignin-derived hard carbon (HCs). By systematic experimental design combined with electron paramagnetic resonance spectroscopy, it can be found that the content of free radicals in the carbon matrix influences the closure of open pores at high temperatures. Excessively high activation temperature (>700 °C) leads to a low free radical concentration, making it difficult to achieve self-healing of open pores at high temperatures. By activation at 700 °C, a balance between pore making and self-healing is achieved in the final hard carbon. A large number of free radicals triggers rapid growth and aggregation of carbon microcrystals, blocking pre-formed open micropores and creating additional interconnected closed pores in as-obtained hard carbons. As a result, the optimized carbon anode (LK-700-1300) delivers a high reversible capacity of 330.8 mA h g−1 at 0.03 A g−1, which is an increase of 86 mA h g−1 compared to the pristine lignin-derived carbon anode (L-700-1300), and exhibits a good rate performance (202.1 mA h g−1 at 1 A g−1). This work provides a universal and effective guidance for tuning closed pores of hard carbons from other precursors.

Implementation of Grey Wolf, Multi-Verse and Ant Lion Metaheuristic Algorithms for Optimizing Machinability of Dry CNC Turning of Annealed and Hardened UNIMAX® Tool Steel

Advances in machining technology and materials science impose the identification of optimal settings for process-related parameters to maintain high quality and process efficiency. Given the available resources, manufacturers should determine an advantageous process parameter range for their settings. In this work, the machinability of a special tool steel (UNIMAX® by Uddeholm, Sweden) under dry CNC turning is investigated. The working material is examined under two states; annealed and hardened. As major machinability indicators, main cutting force Fz (N) and mean surface roughness Ra (μm) were selected and studied under different values for the cutting conditions of cutting speed, feed rate, and depth of cut. A systematic experimental design was established as per the response surface methodology (RSM). The experimental design involved twenty base runs with eight cube points, four center points in the cube, six axial points, and two center points in the axial direction. Corresponding statistical analysis was based on analysis of variance and normal probability plots for residuals. Two regression models referring to main cutting force and surface roughness for both the annealed and hardened states of the material were developed and used as objective functions for subsequent evaluations by three modern meta-heuristics under the goal of machinability optimization, namely multi-objective grey wolf algorithm, multi-objective multi-verse algorithm and multi-objective ant lion algorithm. All algorithms were found capable of providing beneficial Pareto-optimal solutions for both main cutting force and surface roughness simultaneously whilst regression models achieved high correlation among input variables and optimization responses.

Cyclodextrin-Enabled Enantioselective Complexation Study of Cathinone Analogs.

The characteristic alkaloid component of the leaves of the catnip shrub (Catha edulis) is cathinone, and its synthetic analogs form a major group of recreational drugs. Cathinone derivatives are chiral compounds. In the literature, several chiral methods using cyclodextrins (CDs) have been achieved so far for diverse sets of analogs; however, a comprehensive investigation of the stability of their CD complexes has not been performed yet. To characterize the enantioselective complex formation, a systematic experimental design was developed in which a total number of 40 neutral, positively, and negatively charged CD derivatives were screened by affinity capillary electrophoresis and compared according to their cavity size, substituent type, and location. The functional groups responsible for the favorable interactions were identified in the case of para-substituted cathinone analog mephedrone, flephedrone, and 4-methylethcathinone (4-MEC) and in the case of 3,4-methylendioxy derivative butylone and methylenedioxypyrovalerone (MDPV). The succinylated-β-CD and subetadex exhibited the highest complex stabilities among the studied drugs. The complex stoichiometry was determined using the Job's plot method, and the complex structures were further studied using ROESY NMR measurements. The results of our enantioselective complex formation study can facilitate chiral method development and may lead to evaluate potential CD-based antidotes for cathinone analogs.

The fermentation optimization for alkaline protease production by Bacillus subtilis BS-QR-052.

Proteases exhibit a wide range of applications, and among them, alkaline proteases have become a prominent area of research due to their stability in highly alkaline environments. To optimize the production yield and activity of alkaline proteases, researchers are continuously exploring different fermentation conditions and culture medium components. In this paper, the fermentation conditions of the alkaline protease (EC 3.4.21.14) production by Bacillus subtilis BS-QR-052 were optimized, and the effect of different nutrition and fermentation conditions was investigated. Based on the single-variable experiments, the Plackett-Burman design was used to explore the significant factors, and then the optimized fermentation conditions, as well as the interaction between these factors, were evaluated by response surface methodology through the Box-Behnken design. The results showed that 1.03% corn syrup powder, 0.05% MgSO4, 8.02% inoculation volume, 1:1.22 vvm airflow rate, as well as 0.5% corn starch, 0.05% MnSO4, 180 rpm agitation speed, 36°C fermentation temperature, 8.0 initial pH and 96 h incubation time were predicted to be the optimal fermentation conditions. The alkaline protease enzyme activity was estimated to be approximately 1787.91 U/mL, whereas subsequent experimental validation confirmed it reached 1780.03 U/mL, while that of 500 L scale-up fermentation reached 1798.33 U/mL. This study optimized the fermentation conditions for alkaline protease production by B. subtilis through systematic experimental design and data analysis, and the activity of the alkaline protease increased to 300.72% of its original level. The established model for predicting alkaline protease activity was validated, achieving significantly higher levels of enzymatic activity. The findings provide valuable references for further enhancing the yield and activity of alkaline protease, thereby holding substantial practical significance and economic benefits for industrial applications.

Quality by design-assisted development of D-α-tocopherol polyethylene glycol 1000 succinate-incorporated gefitinib-loaded cationic liposome(s).

Aim: Gefitinib-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes (GEF-TPGS-LIPO+) were developed and optimized by the quality by design (QbD) approach for its potential anticancer effect. Methods/materials: Box-Behnken design (BBD) a systematic design of experiments was added to screen and optimize the formulation variables. Results: GEF-TPGS-LIPO+ shows vesicle size (210±4.82nm), polydispersity index(0.271±0.002), zeta potential (22.2±0.84mV) and entrapment efficiency (82.3±1.95). MTT result shows the enhanced cytotoxicity and higher intracellular drug uptake with highest and lowest levels of the reactive oxygen species and NF-κBexpressions on A549 lung cancer cells, determined by fluorescence-activated cell sortingflow cytometry. Conclusion: Potential anticancer effect on A549 cells might be found due to cationic liposomal interaction with cancer cells.

Mechanical properties of a hybrid waste tyre, sisal and polyester resin composite fibre board

Millions of used or worn-out tyres are disposed of by many countries annually. These tyres can be put to good use when recycled. Used tyres are among the most problematic and challenging sources of solid waste, especially in landfills. Therefore, the use of waste tyres for composite materials having desired performance properties can be used as a means of disposing of the tyres. Fibrous material-reinforced composites with enhanced physical and mechanical performance and incorporating sisal fibres were produced using waste tyre material, sisal, and polyester resin. The physical and mechanical properties of hybrid composite board panels, including flexural strength, compression strength, tensile strength, and water absorption, were determined according to ASTM Standards. The rubber tyre particles used in the study had a size of 1.00 mm, and the sisal used had an average length of 6mm. A systematic experimental design was formulated and worked accordingly in the fabrication of the composite. The hybrid composite produced has adequate mechanical properties to perform as a substitute for solid wood in several applications such as tabletops, general purpose, load-bearing boards, ceiling boards, furniture, door panels and partitioning boards.

Improved production of andrimid in Erwinia persicina BST187 strain by fermentation optimization

BackgroundAndrimid is reported to be a novel kind of polyketide-nonribosomal peptide hybrid product (PK-NRPs) that inhibits fatty acid biosynthesis in bacteria. Considering its great potential in biomedicine and biofarming, intensive studies have been conducted to increase the production of andrimid to overcome the excessive costs of chemosynthesis. In screening for species with broad-spectrum antibacterial activity, we detected andrimid in the fermentation products of Erwinia persicina BST187. To increase andrimid production, the BST187 fermentation medium formulation and fermentation conditions were optimized by using systematic design of experiments (One-Factor-At-A-Time, Plackett–Burman design, Response Surface Methodology).ResultsThe results indicate that the actual andrimid production reached 140.3 ± 1.28 mg/L under the optimized conditions (trisodium citrate dihydrate-30 g/L, beef extract-17.1 g/L, MgCl2·6H2O-100 mM, inoculation amount-1%, initial pH-7.0, fermentation time-36 h, temperature-19.7℃), which is 20-fold greater than the initial condition without optimization (7.00 ± 0.40 mg/L), consistent with the improved antibacterial effect of the fermentation supernatant.ConclusionsThe present study provides valuable information for improving andrimid production via optimization of the fermentation process, which will be of great value in the future industrialization of andrimid production.

Improvement of Targeted Fungi Secondary Metabolite Production Using a Systematic Experimental Design and Chemometrics Analysis.

Fungi are well-known producers of chemically diverse and biologically active secondary metabolites. However, their production yields through fermentation may hamper structural analysis and biological activity downstream investigations. Herein, a systematic experimental design that varies multiple cultivation parameters, followed by chemometrics analysis on HPLC-UV-MS or UHPLC-HRMS/MS data, is presented to enhance the production yield of fungal natural products. The overall procedure typically requires 3-4 months of work when first developed, and up to 3 months as a routine procedure.