Low LOD Values Research Articles

Fabrication of Porous Co3O4 Arrays by a Co-Precipitation Method and it Application as a Non-Enzymatic Glucose Sensor

The porous cobaltosic oxide (Co3O4) arrays has been prepared by a chemical co-precipitation route using the nickel foam as s substrate. Cyclic voltammetry (CV), and ampere current method (i-t curve) are used to explore the non-enzymatic glucose sensor in a three-electrode system. This porous Co3O4 array non-enzymatic sensor shows a sensitivity of 592.8 mA mM1 cm2 in concentration from 0.99 M to 1.073 mM. The porous Co3O4 array sensor electrode also showed low LOD value (0.005 M) and fast response time (4 s). This porous Co3O4 electrode shows a good sensor performance due to these rich redox reaction sites in the unique porous structure. This porous cobaltosic oxide arrays maybe a potential sensor material in the glucose detection application

Construction and characterization of nitrite optical sensing nanoplatform based on spectral response

In this paper, two recyclable nitrite sensing platforms were constructed through a core-shell structure, using Fe3O4 nanoparticles as core, a silica molecular sieve MCM-41 as shell and rhodamine molecules as chemosensor, respectively. This hybrid structure was analyzed using electron microscopy images, porous measurement, magnetic analysis, IR spectra and thermal stability. It was found that emission of these two composite samples was quenchable by nitrite through a static sensing mechanism. Low LOD values were obtained for these two composite samples (1.4 µM). In addition, this static sensing reaction could be reversed by sulphamic acid. These two composite samples could be recycled, showing their recyclability.

Synthesis and Fluorimetric Application of Novel Schiff Base Compound Containing Imidazole

This study describes the synthesis and application of 2-(2-hydroxy-5-(1H-phenanthro [9,10-d]imidazol-2-yl)benzylidene)-N-phenylhydrazine-1-carboxamide (TC) as a fluorogenic chemosensor toward for Zn2+ sensing in EtOH-H2O (9:1, v/v) media. The chemosensor TC could sensitively determine Zn2+ ions with a low detection limit (LOD) and LOD value was found to be 5.73 nM. The fluorogenic titration spectrum indicated that the Zn2+ concentration was proportional to emission and gave a good linear alteration in emission in response to the equivalent of Zn2+, the complexation ratio between chemosensor TC and Zn2+ was calculated as 1:1 by the method of continuous variation (Job's plot) from the obtained titration study. Moreover, the Ka value for the TC-Zn2+ complexation was found as 6.7×10−3 M−1 according to the Benesi–Hildebrand value of the changess in the titration of the chemosensor TC against Zn2+ ions. As a result of obtained data, chemosensor TC could be utilized to be an effective fluorogenic chemosensor for recognizing Zn2+ ions.

Push-pull electronic effects on benzothiazole derived probes for the detection of Zn2+: Exploring the sensing strategies and its applications

The diverse polarity of electron-donating 4-(diethylamino)salicylaldehyde (S-D), and electron-withdrawing 4-nitrosalicylaldehyde (S–W) were conjugated with benzothiazole (BT) to develop BTS-D and BTS-W probes, respectively. The probes exhibited the excited-state intramolecular proton transfer and intramolecular charge transfer sensing mechanisms in detecting Zn2+. BTS-D and BTS-W achieved a quantitative detection of Zn2+ followed by a strong cyan to green in the emission spectra, and from colorless to yellow in the UV–Vis spectra, respectively. The sensing pathways and coordination affinities between the probes and Zn2+ were explored using a series of spectroscopic evaluations, 1H NMR, 1H–1H COSY (2D NMR), HR–MS, XPS and DFT calculations. The probes demonstrated excellent selectivity, good water solubility, and high sensitivity, securing low LOD values: 0.15 μM for BTS-W in colorimetric analysis and 14 nM for BTS-D in fluorimetric analysis in aqueous media. The advantages of the probes assessed for the detection of Zn2+ in various water samples, Whatman paper-based sensor strips, and PC3 live cells. The findings revealed the encouraging on-site visualization in wastewater systems and bio-contents.

Accumulation of zoledronic acid in rabbit intervertebral discs

Low back pain is a major chronic musculoskeletal disorder, caused mainly due the degeneration of the intervertebral discs (IVDs). Bisphosphonates (BPs), like zoledronic acid (ZOL), are used in osteoporosis management; however, their accumulation in the IVDs and their physiological role has not been addressed so far. To this end, an SPE-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) analytical method, using on-cartridge derivatization, has been developed and validated. The analytical method presented excellent linearity (R2 > 0.992), high recoveries (67.8–82.6%), increased repeatability (0.5–9.9%) and low LOD values (21 ng g−1 in the case of IVDs) in all matrices studied. The injection of ZOL in a rabbit animal model resulted in rapid accumulation in blood plasma and the skin, followed by quick clearance. On the other hand, no ZOL was detected in nucleus pulposus, the core of the IVD, while in the peripheral annulus fibrosus a lower and delayed accumulation, as well as dispersal was found. These variations are most probably due to the avascular nature of IVD, allowing only the diffusion of small molecules in and out of the tissue, and/or to the unique physicochemical environment of IVDs. Finally, ZOL, at the concentrations found, did not affect cells’ viability or the increase of reactive oxygen species (ROS).

A multi-functional Tb-organic network featuring high selectivity fluorescent sensing for Fe3+, Cr2O72−, tetracycline and 2,4,6-trinitrophenol in aqueous solution

A novel two-dimensional Tb(III)-organic network, named as [Tb2(pyia)3 (phen)2(H2O)]·H2O(1), based on 5-(pyridine-2-ylmethoxy) isophthalic acid (H2pyia) and 1,10-phenanthroline (phen) has been synthesized hydrothermally. Structural analysis shows 1 exhibits two-dimensional network featuring the paddle-wheel binuclear secondary building units [Tb2(COO)4]2-. Fluorescent sensing properties exhibit 1 has been discovered to high selectively and sensitively detect Fe3+ ion (328 ​nM), Cr2O72− anion (526 ​nM), tetracycline (74.8 ​nM) and 2,4,6-trinitrophenol (80 ​nM) with the lower LOD values. Therefore, complex 1 might be used as a multi-response luminescent sensor material.

Designing and application of PPy/Bi2MoO6/chitosan nanocomposites for electrochemical detection of ciprofloxacin and benzene and evaluation of hydrogen evolution reaction.

The excessive use and disposal of antibiotic drugs and toxic solvents in the environment make it necessary to construct and design an efficient, subtle, and reliable sensor for the quantification and control of toxic pollutants. Novel PPy/Bi2MoO6/chitosan nanocomposites have been prepared for the electrochemical detection of ciprofloxacin (fluoroquinolone antibiotic) and benzene. Various spectroscopic and analytical techniques have been utilized for the elucidation of the structural, optical, and morphological properties of the nanocomposites sensors. The particle size of BM, Py-BM and Py-BM-CH1 nanocomposite was calculated to be 15.69 nm, 17.25 nm and 18.57 nm, respectively. The prepared nanocomposites also showed exfoliated morphology which enhances the surface area of the materials. The electroanalytical performance of the catalysts was analyzed via cyclic voltammetry (CV) and electrochemical impedance spectroscopy techniques (EIS). Moreover, the electrochemical detection was comprehensively assessed with linear sweep voltammetry and differential pulse voltammetry. The as-prepared sensor has shown a distinct increase in electrocatalytic and electrochemical activity, which led to its utilization in the electrochemical determination of toxicants, etc. Furthermore, experimental results have confirmed high sensitivity because of the increased surface area and electron mobility of the electrocatalyst. The linear concentration falls into two distinct ranges for both analytes with low LOD value and high sensitivity (0.01 μM to 1500 μM for CIP and 0.05 mM to 500 mM for benzene). Moreover, the nanocomposites have also been evaluated for the estimation of hydrogen evolution reaction, which is a major step in the production of hydrogen. The electrocatalyst has shown low Tafel slopes with low overpotential, reflecting the better electrocatalytic activity of the as-prepared materials.

Determination of methanol and fusel oils in various types of wines distributed in Korea.

The contents of methanol and fusel oils in various types of wines were determined using headspace-gas chromatography (HS-GC). The HS-GC analysis method showed good linearity, high precision and accuracy, and low LOQ and LOD values. The methanol content in 289 types of wines ranged from not detected (ND) to 333.84mg/kg, and was higher in Korean grape wines than in imported grape wines. Among fusel oils, the contents of 1-propanol (23.61-84.23mg/kg) and isobutanol (34.98-111.39mg/kg) were slightly higher in Korean wild grape wines, whereas that of isobutanol (ND to 55.26mg/kg) was slightly lower in Korean black raspberry wine than in the other wines. The contents of amyl alcohol were lower in Korean plum wine and Korean black raspberry wine than in all of the wines included in the present study, and highest in imported grape wines.

A novel, rapid and robust HPLC-ELSD method for simultaneous determination of fructose, glucose and sucrose in various food samples: Method development and validation

The analysis of sugar compounds in food products requires rapid, accurate and cost-effective methods. For this purpose, a novel and robust high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) method was developed and validated for simultaneous determination of fructose, glucose and sucrose. Chromatographic separations were carried out on a Phenomenex Luna NH2 (5 μm particle size, 250 mm x 4.6 mm id, 100 Å) column with isocratic elution with acetonitrile:water (78:22, v/v). Drift tube temperature was set at 40 °C and nitrogen pressure was regulated to 350 kPa with Gain:7 and Filter:10 on the ELSD system. Within the test ranges for all sugar compounds (40-2000 μg mL−1), the regression equation revealed a good linear relationship (R2 = 0.9980−0.9992) with low LOD and LOQ values in the range of 0.10−0.16 and 0.30−0.49 μg mL−1. The method was successfully applied to 36 food samples including honey, molasses, jams and fruits.

Ltrafiltration-based sample preparation and HPLC-UV determination of diclofenac in human plasma samples.

The sample preparation step is the initial step in pharmaceutical analysis. While ultrafiltration is a well-known technique used in the food and pharmaceutical industries, it has rarely been used to measure the plasma concentration of active pharmaceutical ingredients. This study aimed to analyze diclofenac sodium (DS) in human plasma samples using ultrafiltration-based sample preparation before high-performance liquid chromatography (HPLC) analysis. The advantages and limitations of ultrafiltration-based sample preparation in bioanalysis were evaluated by comparing the results with conventional methods. The precipitating agent was used before ultrafiltration. The analysis was carried on an HPLC-UV system with a C18 column (250 ×4.6 mm, 5 μm) and acetonitrile : phosphate buffer (pH 3.0, 10 mM) (70 : 30 v/v) was used as the mobile phase. The bioanalytical method was validated according to FDA guidelines and applied to spiked samples of DS in commercial human plasma samples. The LOD and LOQ values were 0.006 μg mL-1 and 0.020 μg mL-1, respectively. The method was linear in the range of 0.025-0.50 μgmL-1 with excellent determination coefficients (R2 > 0.9991). The findings of this analysis with low LOD and LOQ values and high recovery values with high trueness and precision proved the matrix minimizing the effect of the presented sample preparation technique.

New conductive filament ready-to-use for 3D-printing electrochemical (bio)sensors: Towards the detection of SARS-CoV-2

The 3D printing technology has gained ground due to its wide range of applicability. The development of new conductive filaments contributes significantly to the production of improved electrochemical devices. In this context, we report a simple method to producing an efficient conductive filament, containing graphite within the polymer matrix of PLA, and applied in conjunction with 3D printing technology to generate (bio)sensors without the need for surface activation. The proposed method for producing the conductive filament consists of four steps: (i) mixing graphite and PLA in a heated reflux system; (ii) recrystallization of the composite; (iii) drying and; (iv) extrusion. The produced filament was used for the manufacture of electrochemical 3D printed sensors. The filament and sensor were characterized by physicochemical techniques, such as SEM, TGA, Raman, FTIR as well as electrochemical techniques (EIS and CV). Finally, as a proof-of-concept, the fabricated 3D-printed sensor was applied for the determination of uric acid and dopamine in synthetic urine and used as a platform for the development of a biosensor for the detection of SARS-CoV-2. The developed sensors, without pre-treatment, provided linear ranges of 0.5–150.0 and 5.0–50.0 μmol L−1, with low LOD values (0.07 and 0.11 μmol L−1), for uric acid and dopamine, respectively. The developed biosensor successfully detected SARS-CoV-2 S protein, with a linear range from 5.0 to 75.0 nmol L−1 (0.38 μg mL−1 to 5.74 μg mL−1) and LOD of 1.36 nmol L−1 (0.10 μg mL−1) and sensitivity of 0.17 μA nmol−1 L (0.01 μA μg−1 mL). Therefore, the lab-made produced and the ready-to-use conductive filament is promising and can become an alternative route for the production of different 3D electrochemical (bio)sensors and other types of conductive devices by 3D printing.

PH modulated luminescent switching and discriminative detection of amino acid based on metal-organic framework

The detection of glutamic (Glu) or aspartic (Asp) acids is vital for human nutrition and diagnosis of disease. Herein, the dht ligand containing hydroxy group (-OH) is used to design and synthesize a 2D luminescent [Cd2(idc)(dht)(H2O)4] (1); H2idc = 4,5-imidazoledicarboxylic acid and H2dht = 2,5-dihydroxyterephthalic acid for sensing amino acids. The compound 1 can discriminatively detect Asp and Glu among other amino acids through blue-shifted emission (yellow → green). The dual sensing mechanism may be attributed to the intermolecular excited-state proton transfer between MOF and water to produce keto form along with the subsequent switching of keto form to enol form by protonation causing the increased band gap energy. This material can serve several benefits in terms of high selectivity, fast response (30s), good reproducibility and low LOD value of 11.34 μM which is less than the harmful concentration of Glu for human health (>400 μM). In addition, 1 shows the broad range detection of Glu covering in safe and unsafe levels. For on-site detection of Glu, MOF-based paper is devised and can be applied through color-scanning application in smartphone. Besides, this sensor can serve to detect Glu in real samples with good recovery.

A ratiometric styryl bridging triphenylamine-indolinium based fluorescent dye for detection of cyanide with a large emission shift in human breast cancer cells and test strips

ABSTRACT A new type of styryl bridging triphenyl amine-indolium conjugated dye has been developed for the colorimetric and ratiometric detection of cyanide. The detection of cyanide is confirmed by means of the fast nucleophilic attack of cyanide by the indolium group of the probe that results a speedy sensing process for cyanide with clear color and fluorescence change of the ICT process. The ratiometric fluorescence changes illustrated a linear response in the range of 0-18 μM with a low LOD value (1.7×10-7 M-1). The as-reported sensor not only function as a colorimetric sensor for “in-the-field” measurement by virtue of a “dip-stick” approach but also interact with a human breast cancer cell (MDA-MB 231) which reveals the realistic value of this probe for tracking cyanide anions in biological systems.

Effects of electroactive group and enzyme crosslinkers numbers on analytical performance for conductive polymer-based sensor platforms

This manuscript describes an amperometric sensor application of a new class of triazine-centered monomers functionalized with different numbers of carbazole and hydrazine. In the sensor system, carbazole and hydrazine are designed as transducer and enzyme crosslinker groups, respectively. The monomers (TECA and CTDA) containing different numbers of carbazole and hydrazine were electrochemically polymerized on a graphite (GR) electrode. A new sensor platforms for glucose determination have been obtained by immobilizing glucose oxidase (GOx) on the polymer film surfaces. The pTECA/GOx and pCTDA/GOx-based electrodes were investigated for an evaluation of electron transfer between the enzyme and electrode at bioelectrochemically relevant potentials via pTECA and pCTDA layer. The results show that amperometric response values were greater for the polymer containing more hydrazine ends than the polymer containing more carbazole groups. This is due to the that as the hydrazine ends increased, the more enzyme crosslinker groups at the same surface size. The evaluation of two different configurations (pTECA/GOx and pCTDA/GOx) of working electrodes suggested that the pTECA/GOx configuration, which was composed of more hydrazine ends and enzyme, is the more suitable candidate for biosensor applications. Moreover, it was determined that the pTECA/GOx and pCTDA/GOx-based electrodes are reliable for the establishment of advanced electron transfer between enzyme and electrode for the application in amperometric biosensors because of the observed high amperometric response values, and low LOD values.

Development of a Novel Electrochemical Biosensor Based on Carbon Nanofibers-Cobalt Phthalocyanine-Laccase for the Detection of p-Coumaric Acid in Phytoproducts.

The present paper developed a new enzymatic biosensor whose support is a screen-printed electrode based on carbon nanofibers modified with cobalt phthalocyanine and laccase (CNF-CoPc-Lac/SPE) to determine the p-coumaric acid (PCA) content by cyclic voltammetry and square wave voltammetry. Sensor modification was achieved by the casting and cross-linking technique, using glutaraldehyde as a reticulation agent. The biosensor’s response showed the PCA redox processes in a very stable and sensitive manner. The calibration curve was developed for the concentration range of p-coumaric acid of 0.1–202.5 μM, using cyclic voltammetry and chronoamperometry. The biosensor yielded optimal results for the linearity range 0.4–6.4 μM and stood out by low LOD and LOQ values, i.e., 4.83 × 10−7 M and 1.61 × 10−6 M, respectively. PCA was successfully determined in three phytoproducts of complex composition. The results obtained by the voltammetric method were compared to the ones obtained by the FTIR method. The amount of p-coumaric acid determined by means of CNF-CoPc-Lac/SPE was close to the one obtained by the standard spectrometric method.

QTL mapping for Fusarium wilt resistance based on the whole-genome resequencing and their association with functional genes in Raphanus sativus.

Two major QTL associated with resistance to Fusarium wilt (FW) were identified using whole-genome resequencing. Sequence variations and gene expression level differences suggest that TIR-NBS and LRR-RLK are candidate genes associated with FW-resistance. Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. raphani is an important disease in radish, leading to severe decrease in yield and quality. YR4 as a novel genetic source to resistant to FW was confirmed through screening with five pathogen isolates. We have generated F2 and F2:3 populations segregated with FW resistance using YR4 and YR18 inbred lines. The disease symptom was evaluated in F2:3 population (n = 180) in three independent studies over two years. We identified 4 QTL including the two major QTL (FoRsR7.159A and FoRsR9.359A). FoRsR7.159A and FoRsR9.359A were detected in three replicated experiments. FoRsR7.159A was delimited to the 2.18-Mb physical interval on chromosome R07, with a high LOD value (5.17-12.84) and explained phenotypic variation (9.34%-27.97%). The FoRsR9.359A represented relatively low LOD value (3.38-4.52) and explained phenotypic variation (6.24%-8.82%). On the basis of the re-sequencing data for the parental lines, we identified five putative resistance-related genes and 13 unknown genes with sequence variations at the gene and protein levels. A semi-quantitative RT-PCR analysis revealed that Rs382940 (TIR-NBS) and Rs382200 (RLK) were expressed only in 'YR4' from 0 to 6days after the inoculation. Moreover, Rs382950 (TIR-NBS-LRR) was more highly expressed in 'YR4' from 3 to 6days after the inoculation. These three genes might be important for FW-resistance in radish. We identified several markers based on these potential candidate genes. The marker set should be useful for breeding system to introduce the FW resistance loci from 'YR4' to improve tolerance to FW.

Analytical quality-by-design (AQbD) guided development of a robust HPLC method for the quantification of plumbagin from Plumbago species

The present study was framed with the aim to develop a simple, efficient, and robust reverse-phase HPLC method for the quantification of plumbagin utilizing an analytical quality-by-design (AQbD) approach. HPLC was performed in Waters made high-performance liquid chromatography equipped with Waters 2996 photodiode array detector (detection at 254 nm), and reversed-phase Waters inertsil C18 column. The AQbD approach helps in finding the most suitable critical analytical attributes (CAAs) as well as high-risk critical method parameters (CMPs). Using the Box-Behnken Design experiment, the selected CMPs were optimized for the higher recovery of plumbagin. Further, the developed method was validated following International Conference on Harmonization (ICH) Q2 (R1) guidelines. The low divergence in intra- and inter-day experiments, and low LOD (2.4 µg/mL) and LOQ (7.2 µg/mL) values justify the high precision and sensitivity of the developed method. The developed method was further tested for the quantification of plumbagin from the two different plant source collected from two different climatic conditions. Results show that the maximum plumbagin content was found in P. indica roots. In conclusion, the AQbD approach could be used in other plant systems for the optimization of different variables to obtain a higher amount of targeted plant metabolite.

Photophysical Investigation of a Benzimidazole Derivative and Its Applications in Selective Detection of Fe3+, Thermosensing and Logic Gates.

The fluorescence based applications such as chemosensing of Fe3+ ion, temperature sensing, NOR-gate molecular logic operations, and fluorescent ink were achieved using an expired medicine namely Pantoprazole (sensor1) which is a derivative of benzimidazole class. The phenomenon of quenching was a basic principle used in sensing Fe3+. We found that there was a combined effect of dynamic and static processes in quenching of fluorescence of sensor1. To confirm the selectiveness of sensor1, we performed interference experiments with other metal ions. There was no interference between these metal ions and Fe3+. The low LOD value of 1.032µM suggested that the molecule is highly sensitive towards Fe3+. A high quantum yield of 8.087% increased the possibility of using sensor1 for light applications. There was a 2:1 stoichiometric ratio between sensor1 and Fe3+. The FTIR data analysis confirmed the presence of functional groups S = O, C-O-C, etc. The average particle size found with the DLS method was 130.5nm. The zeta potential of -12.7mV indicated that sensor1 is quite stable in solution form. For logic gate application EDTA (Ethylenediaminetetraaceticacid) and Fe3+ were considered as inputs and fluorescence intensity was taken as an output. In thermal sensing application, the high value of activation energy i.e. 908meV and relative sensitivity of 1.2% 0C-1 affirmed that sensor1 can be used for thermal applications. The sensor1 was also apt for fluorescent ink application. Hence this investigation deduced that sensor1 can be a potential candidate for such applications over other conventional synthesized fluorescent probes.

Five spectrophotometric methods for simultaneous determination of Amlodipine besylate and celecoxib in presence of its toxic impurity

Five simple, selective and accurate spectrophotometric methods have been applied and developed for first time for simultaneous determination of amlodipine besylate (AML) and celecoxib (CEL) in presence of one harmful impurity, 4-methylacetophenone (MAP), in their ternary mixture without prior separation. Those spectrophotometric methods were developed and called: dual wave length in ratio spectra (DWRS), successive ratio-derivative spectra (SDR), modified absorption factor method (MAFM), modified amplitude center method (MACM) and first derivative –zero crossing coupled with amplitude factor method (FDAF). These methods include various steps using zero /or ratio /or derivative spectra and some mathematical techniques. Linear calibration curves were constructed over the concentration range of 2–100, 10–200 and 0.5–20 µg/mL for AML, CEL and MAP, respectively. High sensitivity with low LOD values 0.583, 3.118 and 0.147 for AML, CEL and MAP, respectively were obtained. Moreover, validation of the proposed methods was achieved according to ICH guidelines and satisfactory results were obtained indicating that the developed methods can be used for quality control analysis of AML and CEL concerning its impurity. No significant difference was observed when the obtained results of the developed methods were statistically compared with the reported HPLC method.

A versatile method for the quantification of 100 SVOCs from various families: Application to indoor air, dust and bioaccessibility evaluation

A method coupling automated thermal desorption (ATD) with in-tube derivatization and solid phase micro-extraction (SPME), with on-injector derivatization gas chromatography - tandem mass spectrometry (GC/MSMS) was developed and used for the simultaneous quantification of 100 semivolatile (SVOCs) pollutants (50 pesticides, 16 PAHs, 22 PCBs, 7 phthalates and 5 alkylphenols) in indoor air, indoor dust, and for bioaccessibility evaluation. Chemical compounds in indoor air were sampled on Tenax-TA passive samplers (PAS) exposed for 15 days, while dust was collected on silicon carbide (SiC©) foam using a custom made vacuum cleaner head. After sampling, Tenax tubes from PAS were introduced directly into a thermal desorption tube while dust was extracted using accelerated solvent extractor (ASE). Extract is then used to spike clean Tenax-TA tube that is then treated as a Tenax from PAS. The derivatization agent (MtBSTFA) and a mix of internal standards were added into the tubes before thermal desorption and analysis by GC/MSMS.The SPME technique was applied to extract the 100 SVOCs from the different tested bioaccessibility solutions (saliva, gastric, intestinal).This method permits the determination of 100 pollutants in a single run, including those requiring a derivatization step, with very low quantification and detection limits. Indeed, ATD-GC/MSMS technic presents very low LOD (0.002 to 0.17 ng) and LOQ (0.007 to 0.56 ng) values while SPME-GC/MSMS displays slightly higher LOD (0.044 to 12.3 ng) and LOQ (0.10 to 37.0 ng) ranges.