Complicated Sample Pretreatment Research Articles

Rapid Determination of Adenine Arabinoside Monophosphate in Pharmaceutical Injections by Droplet Spray Ionization – Tandem Mass Spectrometry (DSI-MS/MS)

Rapid analysis of pharmaceutical preparations is of great interest in clinical studies with benefits for identifying counterfeit drugs. In this study, droplet spray ionization tandem mass spectrometry (DSI-MS/MS) was developed for the rapid determination of adenine arabinoside monophosphate in pharmaceutical injections without complex sample pretreatment. The sample solution was loaded on the slip corner placed in front of the inlet of a mass spectrometer, and high voltage was applied to the solution to create a charged spray from the corner for MS analysis. The sample was loaded for analysis without additional sample preparation protocols, which greatly simplifies the operation. The limit of detection and limit of quantification were determined to be 2.7 and 9.1 ng/mL, respectively. The recoveries were in the range from 96% to 112%, and the calculated relative standard deviations were less than 7% for the DSI-MS/MS method. Three adenine arabinoside monophosphate pharmaceutical injection samples and a degraded sample obtained by acid treatment at 40 °C were successfully analyzed by directly dissolving and diluting the sample. Moreover, the sample-loading step required only 2 s. Together these capabilities indicate that the DSI-MS/MS is a simple and robust method and has promising applications in pharmacology studies without complicated sample pretreatment.

Photoacoustic Spectrometric Evaluation of Soil Heavy Metal Contaminants

Heavy metal pollution in soil has severe impact on the human health and global environment. There is an urgent need for cost-effective devices capable of recognizing and detecting heavy metallic matters in soils. A broadband photoacoustic spectrometric (PAS) system was established for the detection of heavy metal contaminants in soil. The heavy metal element lead (Pb) was selected as a preferred detection target. The near infrared photoacoustic spectra of contaminated soil samples with various concentrations of Pb were collected and the spectroscopic relationship between the soil absorption peaks and Pb concentrations was analyzed. Four advanced spectral preprocessing methods were explored to improve the robustness of the prediction model. Based on the maximal correlation coefficient and minimal root mean square error criteria of prediction, a two-layer feed-forward network with a continuum removing preprocessing method with a correlation coefficient as 0.96 was tested as the most appropriate method for Pb concentration prediction. This fact verifies that the broadband PAS evaluation methodology, as a nondestructive testing method, can be potentially used as an alternative quantification detection method of heavy metal contaminants in soil without the involvement of complicated sample pretreatment.

A glassy carbon electrode modified with a copper tungstate and polyaniline nanocomposite for voltammetric determination of quercetin

A binary nanocomposite of type copper tungstate and polyaniline (CuWO4@PANI) is described that was obtained by single step polymerization on the surface of a glassy carbon electrode (GCE). The resulting electrode is shown to be a viable tool for voltammetric sensing of quercetin (Qn) in blood, urine and certain food samples. The nanocomposite was characterized by UV-visible absorption spectroscopy, Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction and high-resolution transmission electron microscopy. Differential pulse voltammetry was applied to quantify Qn, typically at the relatively low working potential of 0.15V (vs. Ag/AgCl). The modified GCE has a wide analytical range (0.001-0.500μM) and a low detection limit (1.2nM). The sensor is reproducible, selective and stable. This makes it suitable for determination of Qn in real samples without complicated sample pretreatment. Graphical abstract Schematic of a copper tungstate and polyaniline nanocomposite modified glassy carbon electrode for voltammetric determination of quercetin in real samples.

Ultrasensitive Virion Immunoassay Platform with Dual-Modality Based on a Multifunctional Aggregation-Induced Emission Luminogen.

Sensitive and accurate detection of highly contagious virus is urgently demanded for disease diagnosis and treatment. Herein, based on a multifunctional aggregation-induced emission luminogen (AIEgen), a dual-modality readout immunoassay platform for ultrasensitive detection of viruses has been successfully demonstrated. The platform is relied on virions immuno-bridged enzymatic hydrolysis of AIEgen, accompanying with the in situ formation of highly emissive AIE aggregates and shelling of silver on gold nanoparticles. As a result, robust turn-on fluorescence and naked-eye discernible plasmonic colorimetry composed dual-signal is achieved. By further taking advantage of effective immunomagnetic enrichment, EV71 virions, as an example, can be specifically detected with a limit of detection down to 1.4 copies/μL under fluorescence modality. Additionally, semiquantitative discerning of EV71 virions is realized in a broad range from 1.3 × 103 to 2.5 × 106 copies/μL with the naked eye. Most importantly, EV71 virions in 24 real clinical samples are successfully diagnosed with 100% accuracy. Comparing to the gold standard polymerase chain reaction (PCR) assay, our immunoassay platform do not need complicated sample pretreatment and expensive instruments. This dual-modality strategy builds a good capability for both colorimetry based convenient preliminary screening and fluorescence based accurate diagnosis of suspect infections in virus-stricken areas.

Determination of diclofenac sodium by resonance light scattering method using silver nanoparticles as probe

A sensitive, simple and novel method was developed to determine diclofenac sodium (DS) using silver nanoparticles (AgNPs) as probe by resonance light scattering (RLS) technique. It was found that DS could quench the RLS intensity of AgNPs. Moreover, the decrease in RLS intensity was linearly correlated to the concentration of DS over the range of 0.01–2.0μgmL−1. DS can be measured in a short time (5min) without any complicated or time-consuming sample pretreatment process. Parameters that affect the RLS intensities such as pH, concentration of AgNPs, reaction time, electrolyte concentration, and coexisting substances were systematically investigated and optimized. The results showed that the method had a very good selectivity and could be used conveniently for the determination of DS. The limit of detection (LOD) was 2.85ngmL−1 (3σ), and the relative standard deviation (RSD) was less than 3.6% (n=6). Possible mechanism for the RLS changes of AgNPs in the presence of DS was discussed and the method was successfully applied for the analysis of tablets and urine samples.

N-doped carbon nanotubes-reinforced hollow fiber solid-phase microextraction coupled with high performance liquid chromatography for the determination of phytohormones in tomatoes

A N-doped carbon nanotubes-reinforced hollow fiber solid-phase microextraction (N-doped CNTs-HF-SPME) method was developed for determination of two naphthalene-derived phytohormones, 1-naphthalene acetic acid (NAA) and 2-naphthoxyacetic acid (2-NOA), at trace levels in tomatoes. N-doped CNTs were dispersed in ultrapure water with the assistance of surfactant, and then immobilized into the pores of hollow fiber by capillary forces and sonification. The resultant N-doped CNTs-HF was wetted with 1-octanol, subsequently immersed into the tomato samples to extract the target analytes under a magnetic stirring, and then desorbed with methanol by sonication prior to chromatographic analysis. Compared with CNTs, the surface hydrophilicity of N-doped CNTs was improved owing to the doping of nitrogen atoms, and a uniform dispersion was formed, thus greatly simplifying the preparation process and reducing waste of materials. In addition, N-doped CNTs-HF exhibits a more effective extraction performance for NAA and 2-NOA on account of the introduction of Lewis-basic nitrogen. It is worth to mention that owing to the clean-up function of HF, there are not any complicated sample pretreatment procedures prior to the microextraction. To achieve the highest extraction efficiency, important microextraction parameters including the length and the concentration level of N-doped CNTs in surfactant solution, extraction time, desorption conditions such as the type and volume of solvents, pH value, stirring rate and volume of the donor phase were thoroughly investigated and optimized. Under the optimal conditions, the method showed 165- and 123-fold enrichment factors of NAA and 2-NOA, good inter-fiber repeatability and batch-to-batch reproducibility, good linearity with correlation coefficients higher than 0.9990, low limits of detection and quantification (at ng g−1 levels), and satisfactory recoveries in the range of 83.10–108.32% at three spiked levels. The proposed method taking advantages of both excellent adsorption performance of N-doped CNTs and the clean-up function of HF, was a simple, green, efficient and cost-effective enrichment procedure for the determination of trace NAA and 2-NOA in tomatoes.

Target binding and DNA hybridization-induced gold nanoparticle aggregation for colorimetric detection of thrombin

We present here a simple and sensitive sensing strategy for thrombin in buffer solution and human serum samples. The key features of this assay lie in target binding-induced DNA hybridization and the formation of gold nanoparticle (AuNP) aggregation. In the presence of thrombin, the binding of the two DNA strands to the same target triggers the hybridization between the complementary sequences of the two DNA strands. The hybridization is able to pull a few AuNPs together to form oligomers. A linear dependence between the absorbance and target thrombin concentration is obtained under optimal conditions in the range from 10 nM–5 μM with a detection limit (LOD) of 7.5 nM estimated at the 3Sblank level. Moreover, this method is successfully applied to complex serum samples without complicated sample pretreatment and sophisticated instruments, a dynamic range (10 nM–5 μM) and a detection limit as low as 9.1 nM is achieved.

Label-free determination of prostate specific membrane antigen in human whole blood at nanomolar levels by magnetically assisted surface enhanced Raman spectroscopy

Prostate cancer is one of the most common cancers among men and can in its later stages cause serious medical problems. Due to the limited suitability of current diagnostic biochemical markers, new biomarkers for the detection of prostate cancer are highly sought after. An ideal biomarker should serve as a reliable prognostic marker, be applicable for early diagnosis, and be applicable for monitoring of therapeutic response. One potential candidate is glutamate carboxypeptidase II (GCPII), also known as prostate specific membrane antigen (PSMA), which has a promising role for direct imaging. GCPII is considerably over-expressed on cancerous prostatic epithelial cells; its analysis typically follows radiological or spectrophotometric principles. Its role as a biomarker present in blood has been recently investigated and potential correlation between a concentration of GCPII and prostate cancer has been proposed. The wider inclusion of GCPII detection in clinical praxis limits mainly the time and cost per analysis. Here, we present a novel analytical nanosensor applicable to quantification of GCPII in human whole blood consisted of Fe3O4@Ag magnetic nanocomposite surface-functionalized by an artificial antibody (low-molecular-weight GCPII synthetic inhibitor). The nanocomposite allows a simple magnetic isolation of GCPII using external magnetic force and its consecutive determination by magnetically assisted surface enhanced Raman spectroscopy (MA-SERS) with a limit of detection 6 pmol. L−1. This method enables a rapid determination of picomolar concentrations of GCPII in whole human blood of healthy individuals using a standard addition method without a complicated sample pre-treatment.

A “turn-on” fluorescence sensor for Pb2+ detection based on graphene quantum dots and gold nanoparticles

Heavy metal, such as Pb2+, detection technologies are quite important in environment monitoring and human health protection. However, most existing technologies are often time consuming, expensive with sophisticated equipment, and requirement of complicated sample pre-treatment, which limit the useful range of real-time application. Here, we report the development of a “turn-on” fluorescence sensor for Pb2+ detection based on graphene quantum dots and gold nanoparticles. We achieved an extremely broad detection range of Pb2+ from 50nM to 4μM, with a detection limit of 16.7nM. This sensing system is highly sensitive and selective for determination of Pb2+. The proposed strategy is expected to provide considerable implication for other heavy metal, antigen, or DNAs by modifying sensing molecules, and fast examination in chemical and biological applications.

Freshness assessment of intact fish via 2D 1H J-resolved NMR spectroscopy combined with pattern recognition methods

Freshness of intact zebrafish was evaluated by 2D 1H J-resolved NMR spectroscopy conjugated with pattern recognition methods Without complicated sample pretreatment and specialized hardware settings, the biochemical processes of intact zebrafish from fresh to decay state and the corresponding metabolite profiles were acquired. A total of 21 metabolites were identified and their concentration variations during the spoilage process were obtained. Pattern recognition models were established for discrimination of fish from freshness to decomposition status. The results show that the concentration of lipid declines, the concentration of lactate fluctuates, and the concentrations of glycerol, asparagine, sarcosine, tyrosine, acetate, glycine and serine increase over the storage time. The observed acetate accumulation and lactate consumption may be considered as indexes for fish freshness assessment. This study indicates that the combination of high-resolution 2D 1H J-resolved NMR spectroscopy and pattern recognition methods may provide an efficient way for quality evaluation of semisolid and viscous foods.

Colorimetric detection of Ag+ based on C[sbnd]Ag+[sbnd]C binding as a bridge between gold nanoparticles

We have developed aptamer-functionalized gold nanoparticles (AuNPs) for the rapid, selective, and sensitive detection of Ag+ in aqueous solution. Two DNA strands are designed to functionalized on the surface of AuNPs through AuS bond. In the presence of Ag+, aptamer1 hybridizes with the partially complementary aptamer2 with the aid of CAg+C bindings, which could lead to different degrees of AuNP aggregation. This process is accompanied by a color change from red to bluish-purple as observed by naked eyes. This colorimetric sensor is shown to detect the presence of as low as a 0.236nM concentration of Ag+. Importantly, it could be applied to complex samples without complicated sample pretreatment and sophisticated instruments.

Highly Sensitive Naked-Eye Assay for Enterovirus 71 Detection Based on Catalytic Nanoparticle Aggregation and Immunomagnetic Amplification.

Development of sensitive, convenient, and cost-effective virus detection product is of great significance to meet the growing demand of clinical diagnosis at the early stage of virus infection. Herein, a naked-eye readout of immunoassay by means of virion bridged catalase-mediated in situ reduction of gold ions and growth of nanoparticles, has been successfully proposed for rapid visual detection of Enterovirus 71 (EV71). Through tailoring the morphologies of the produced gold nanoparticles (GNPs) varying between dispersion and aggregation, a distinguishing color changing was ready for observation. This colorimetric detection assay, by further orchestrating the efficient magnetic enrichment and the high catalytic activity of enzyme, is managed to realize highly sensitive detection of EV71 virions with the limit of detection (LOD) down to 0.65 ng/mL. Our proposed method showed a much lower LOD value than the commercial ELISA for EV71 virion detection. Comparing to the current clinical gold standard polymerase chain reaction (PCR) method, our strategy provided the same diagnostic outcomes after testing real clinical samples. Besides, this strategy has no need of complicated sample pretreatment or expensive instruments. Our presented naked-eye immunoassay method holds a promising prospect for the early detection of virus-infectious disease especially in resource-constrained settings.

Characterization of organic aerosol in Beijing by laser desorption ionization coupled with Fourier Transform Ion Cyclotron Resonance Mass spectrometry

In order to resolve the organic compositions in the atmospheric aerosol which is significant for understanding the formation mechanism of particulate matter and their harm for human health, a direct laser desorption ionization (LDI) coupled with Fourier Transform Resonance Mass (FT-ICR MS) was utilized for characterizing the aerosol particles collected in Beijing during winter. A lot of organic compounds can be detected by direct laser desorption ionization of the aerosol particular with different size collected on aluminum foil without complicated sample pretreatment process. In addition, semi quantification of the organic compounds can be achieved with solvent extraction procedure. It was found that the ubiquitous polycyclic aromatic hydrocarbons (PAHs) contaminants in the aerosol could serve as matrix, which helps the detection of many kinds of compounds including highly saturated amphiphilic long alkyl chain compounds (carbon number>16), like aliphatic amines in positive ion mode and organosulfates in negative ion mode. Based on the accurate mass measurement results, elemental compositions of over 1500 peaks in the mass spectrum were derived, and we categorized them into five groups according to their elemental compositions in order to provide helpful information for tracing the pollution source. It is demonstrated that abundant information about the organic components in the atmospheric aerosol can be provided by direct LDI FT-ICR MS method, and these information will largely facilitate further studies on origin and formation process of the aerosol.

Development of "Laser Ablation Direct Analysis in Real Time Imaging" Mass Spectrometry: Application to Spatial Distribution Mapping of Metabolites Along the Biosynthetic Cascade Leading to Synthesis of Atropine and Scopolamine in Plant Tissue.

Methods for the accomplishment of small-molecule imaging by mass spectrometry are challenged by the need for sample pretreatment steps, such as cryo-sectioning, dehydration, chemical fixation, or application of a matrix or solvent, that must be performed to obtain interpretable spatial distribution data. Furthermore, these steps along with requirements of the mass analyzer such as high vacuum, can severely limit the range of sample types that can be analyzed by this powerful method. Here, we report the development of a laser ablation-direct analysis in real time imaging mass spectrometry approach which couples a 213 nm Nd:YAG solid state UV laser to a direct analysis in a real time ion source and high-resolution time-of-flight mass spectrometer. This platform enables facile determination of the spatial distribution of small-molecules spanning a range of polarities in a diversity of sample types and requires no matrix, vacuum, solvent, or complicated sample pretreatment steps. It furnishes high-resolution data, can be performed under ambient conditions on samples in their native form, and results in little to no fragmentation of analytes. We demonstrate its application through determination of the spatial distribution of molecules involved in the biosynthetic cascade leading to formation of the clinically relevant alkaloids atropine and scopolamine in Datura leichhardtii seed tissue.

Determining lead, cadmium and mercury in cosmetics using sweeping via dynamic chelation by capillary electrophoresis.

International limits have been established for metal impurities in cosmetics to prevent overexposure to heavy metal ions. Sweeping via dynamic chelation was developed using capillary electrophoresis to analyze lead (Pb), cadmium (Cd) and mercury (Hg) impurities in cosmetics. The sweeping via dynamic chelation mechanism involves a large volume of metal ions being swept by a small quantity of chelating agents that were electrokinetically injected into the capillary to chelate metal ions and increase the detection sensitivity. The optimized conditions were as follows: Firstly, the capillary was rinsed by a 0.6mM TTAB solution to reverse the EOF. The sample solution, which was diluted using 25mM ammonium acetate (pH6.0), was injected into the capillary using a pressure of 3.5psi for 99.9s. Then, EDTA was injected at -25kV for 1min from the EDTA buffer (25mM ammonium acetate containing 0.6mM TTAB and 5mM EDTA), and the metal ions were swept and stacked simultaneously. Finally, the separation was performed at -20kV using a separation buffer (100mM ammonium acetate (pH6.0)). A small quantity of chelating agents introduced into the capillary could yield 33-, 50- and 100-fold detection improvements for Pb, Cd and Hg, respectively, more sensitive than conventional capillary zone electrophoresis. Correlation coefficients greater than 0.998 indicated that this method exhibited good linearity. The relative standard deviation and relative error were less than 8.7%, indicating high precision and accuracy. The recovery value of the homemade lotion, which was employed to simulate the real sample matrix, was 93-104%, which indicated that the sample matrix does not affect the quantitative results. Finally, commercial cosmetics were employed to demonstrate the feasibility of the method to determine Pb, Cd and Hg without complicated sample pretreatment. Graphical Abstract The procedure of analyzing metal ions in cosmetics by sweeping via dynamic chelation.

Direct and ultrasensitive optofluidic-based immunosensing assay of aflatoxin M1 in dairy products using organic solvent extraction

Aflatoxin M1 (AFM1), a highly toxic secondary metabolite, is present in a wide range of dairy products. In this study, we designed a simple, low-cost, reusable, and easy-to-operate immunosensing method for ultrasensitive detection of AFM1 in dairy products by using a portable evanescent wave-based optofluidic biosensing platform (EOBP). The developed method provides the minimum detection limit of 5 ng/L, which is below the most restrictive standard imposed by the current regulations for AFM1 in dairy products. The effect of several organic solvents, such as methanol, acetone, and acetonitrile, on the binding reaction of antibody-antigen in heterogeneous and homogeneous solutions was evaluated. Although the effect of organic solvents on the homogeneous binding reaction between antibody and antigen is more significant than that of heterogeneous binding reaction between antibody in solution and antigen immobilized onto the sensor surface, the fluorescence signal detected by EOBP is linearly dependent on AFM1 concentration. Therefore, AFM1 can be directly quantified even if the samples contain a certain organic solvent concentration. The robustness and stability of AFM1-ovalbumin conjugate allow the regeneration of modified biosensor surface for more than 200 times, thereby achieving a cost-effective and reliable AFM1 determination. The proposed method provides a rapid, ultrasensitive, and reliable AFM1 determination in dairy products without complicated sample pretreatment process.

Glutathione-capped Mn-doped ZnS quantum dots as a room-temperature phosphorescence sensor for the detection of Pb2 + ions

The room-temperature phosphorescence (RTP) of glutathione-capped Mn-doped ZnS quantum dots (GSH-Mn-ZnS QDs) was effectively quenched by the addition of Pb2+. A simple and sensitive RTP sensor for Pb2+ detection based on the quenching effect was developed. Under the optimal conditions, good linear correlations were obtained for Pb2+ over a concentration range from 1.0 to 100μg·L−1, and the detection limit was 0.45μg·L−1. The established method has been successfully applied for the determination of Pb2+ in real water samples without complicated sample pretreatment with the recoveries in the range of 95.4%–104.0%.

A novel immunochromatographic assay based on a time-resolved chemiluminescence strategy for the multiplexed detection of ractopamine and clenbuterol

A novel multiplexed immunochromatographic assay (ICA) based on a time-resolved chemiluminescence (CL) strategy was developed for quantitative detection of β-agonists, by utilizing ractopamine (RAC) and clenbuterol (CLE) as the models. Different from conventional multiplexed ICA methods which usually require two or more test lines, this strategy was developed for detection of two β-agonists by using only one test line on the nitrocellulose membrane. In this study, horseradish peroxidase and alkaline phosphatase were used as the signal probes to label RAC antibody and CLE antibody, respectively. The two CL reactions with flash type and glow type kinetics characteristics were triggered simultaneously by injecting the coreactants, then the signals for RAC and CLE detections were recorded at 3 s and 300 s after coreactants injection, respectively. Owing to the utilization of CL detection, this protocol showed ideal sensitivity for quantitation. Under the optimal conditions, the detection limits for RAC and CLE were 0.17 ng mL−1 and 0.067 ng mL−1 (S/N = 3), respectively. The whole assay process can be accomplished within 20 min without complicated sample pretreatment. The proposed method was successfully applied for the detection of RAC and CLE in spiked swine urine. It opens up a new pathway for designing a low cost, time-efficiency and multiplexed strategy for rapid screening and field assay.

A QuEChERS/LC–MS method for the analysis of ractopamine in pork

The development of rapid, high sample throughput methods is constantly demanded by food analytical laboratories. Several current methods for the analysis of ractopamine deal with time-consuming procedures or complicated sample pretreatment steps. Thus, this study aimed to validate and to optimize a simple method for the extraction of ractopamine from pork using a “Quick, Easy, Cheap, Effective, Rugged and Safe” (QuEChERS) approach. Extraction was carried out with an acetonitrile acidic solution and then sodium chloride was used to promote salting out, increasing the solubility of ractopamine. Anhydrous magnesium sulfate was added to remove water and the clean-up was carried out with C18 and primary/secondary amine. Ractopamine was then determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS) within 4.5min only, before a single extraction procedure. Full validation was performed in accordance to Commission Decision 2002/657/EC. Additionally, matrix effect, limit of detection (LoD), limit of quantitation (LoQ) and measurement uncertainty were also determined. Linear range was among 2.5–20μg/kg. LoD and LoQ were set to 1.5μg/kg and 2.5μg/kg, respectively, being below the maximum residue limit established by most countries. A high throughput screening and confirmatory tool, combined with a cheap and fast sample pretreatment method was developed. The method proved to be reproducible and sensitive and its applicability was checked on several samples of pork and pork products, with results that ranged from below LoQ to 6.54μg/kg.

Ultrafast colorimetric determination of predominant protein structure evolution with gold nanoplasmonic particles.

The intracellular and extracellular accumulation of disordered proteins and aggregated proteins occurs in many protein conformational diseases, such as aging-related neurodegeneration and alcoholic liver diseases. However, the conventional methods to study protein structural changes are limited for the rapid detection and monitoring of protein aggregation because of long incubation times (i.e., usually several days), complicated sample pretreatment steps, and expensive instrumentation. Here, we describe an ultrafast colorimetric method for the real-time monitoring of protein structure evolution and the determination of predominant structures via nanoparticle-assisted protein aggregation. During the aggregation process, nanoparticles act as nucleation cores, which form networks depending on the structures of the protein aggregates, and accelerate the kinetics of the protein aggregation. Simultaneously, these nanoparticles exhibit colorimetric responses according to their embedded shapes (e.g., fibrillar and amorphous) on the protein aggregates. We observed distinct spectral shifts and concomitant colorimetric responses of concentration- and type-dependent protein aggregation with the naked eye within a few minutes (<2 min) under acidic conditions. Moreover, the morphological transitions from small aggregates to larger aggregates of nanoparticle-assisted protein aggregates were visualized with dark-field microscope imaging, which show a similar trend with that of protein aggregates formed without the aid of nanoparticles. Finally we show that our proposed method can be utilized to screen the protein aggregation propensity under a variety of conditions such as different pH levels, high temperature, and chemicals. These findings suggest that the proposed method is an easy way to study the molecular biophysics of protein aggregation and to rapidly screen anti-aggregation drugs for protein conformational diseases.