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News Article | May 10, 2017
Site: www.nature.com

In 2013, Huang Song walked into a printing shop in northwestern Beijing and stumbled upon evidence of a brazen and widespread criminal enterprise. Huang was just 15 kilometres from Beijing’s National Institute of Biological Sciences, where he does synthetic-biology research. Scouting out a small desktop machine to produce the hundreds of labels needed for his experiments, he asked if a certain model could print on heat-resistant paper. The shop owner proudly pulled out some samples he had made for customers using the same machine. Huang was shocked to see names such as Abcam and Cell Signaling Technology on labels that looked exactly like those on vials of expensive antibodies produced by the Western companies. Although the writing meant nothing to the friendly shop owner, for Huang it directly corroborated what he and a number of his colleagues had long suspected: many of the antibodies sold by Chinese distributors were not what they were supposed to be. Counterfeiters were getting fake and diluted research reagents on to the market, and this shop in Zhongguancun, Beijing’s premier technology park, was one of the places they were buying machines to make their labels. “I had a suspicion. That confirmed it,” Huang says. China is famous for knock-off DVDs, Louis Vuitton bags and Rolex watches. But counterfeit reagents aren’t on sale in busy public markets. They are sold through sophisticated websites, mixed in with legitimate supplies, and sourced and sold using a network of unwitting partners, such as the Zhongguancun shopkeeper. Even university cleaning staff have been implicated in the hidden process that creates counterfeit laboratory products, including basic chemistry reagents, serum for cell culture and standard laboratory test kits. Although it’s difficult to quantify the effects of this illegal trade, Chinese scientists and some in Europe and North America say that fake products have led them astray, wasting time and materials. Some in China fear that the problem could undermine the country’s efforts to become a world leader in science. Options for combating the counterfeiters are limited. Reagent companies whose brands are tarnished — and the scientists taken in by fakes — shy away from legal action, partly because of embarrassment and partly because they have little faith that law-enforcement agencies can make much of a dent in the trade. “You cannot stop them from trying. The profit margin is just too high,” says Huang. Scientists and suppliers are now devising strategies that could help change the equation. Major reagent manufacturers have launched educational campaigns. Scientists are sharing their tales of frustration, along with tips for avoiding fraudulent supplies. And Huang has helped to establish a partly government-owned reagent-importing enterprise that takes advantage of new customs and quarantine procedures — something that could help shrink the market for fakes. But these measures won’t help everyone. Researchers at universities and institutes outside hubs such as Beijing and Shanghai are especially at risk. “I know a lot of labs who still buy and use fake imported chemical reagents,” says Can Xie, a biophysicist at Peking University in Beijing. “I feel sorry for them.” China is an attractive target for this specialized form of counterfeiting. Investment in research has expanded rapidly — the biomedical-science budget for the National Natural Science Foundation of China has quadrupled over the past decade. And the sheer size of the country means that foreign companies, unable to keep up with demand and loath to navigate China’s tricky distribution system, have become dependent on local distributors. “The country poses many distribution challenges and shipping is logistically difficult,” says Jay Dong, global vice-president and Asia Pacific general manager for Cell Signaling Technology, an antibody manufacturer based in Danvers, Massachusetts. So local companies often carry out the much-needed role of distribution. Some are authorized by the manufacturers. Many are not, however, and it is often difficult for scientists to tell the difference, says Jack Leng, chief executive of Shanghai Universal Biotech, one of the largest distributors of antibodies in China. Disreputable merchants can take advantage of the inflated prices and long waits created by China’s laborious customs and quality-control measures. They offer low prices and fast service for what appear to be the same products, sometimes claiming that the goods have been smuggled into the country. “We do notice counterfeiting in China more than other countries,” Dong says. Xie, who worked in the United States as a postdoc, says that it took him a few years after his return to China in 2009 to realize that some chemical reagents he was buying were sub par. Distributors, he says, claimed to represent foreign companies with premium products, but were actually selling cheap, domestically produced versions. He cannot say conclusively that impure, low-quality reagents were to blame for failed experiments, but he adds that “mysterious, insoluble stuff” he found in some solutions should have been a warning sign. He now buys only from well-known companies with branch offices in China. Huang, who is deputy director of administration at his institute, witnessed a colleague facing similar frustrations in 2012, when, for six months after publishing a paper, he found that he couldn’t repeat the results of some experiments. The researcher went through all the normal troubleshooting steps and asked colleagues for help. Finally, he discovered that a reagent used to introduce DNA into cells was hampering his replication efforts. Huang now attributes the problems to a counterfeit. “The last thing you think about is the reagent,” he says. “This is the kind of stress you cannot put a price on.” Counterfeit antibodies are a particularly widespread source of frustration. Antibodies are crucial in a variety of biological experiments, offering the ability to label and track proteins in a range of living systems. But even untainted ones present some difficulties: there can be natural variation from batch to batch, and they may target unanticipated proteins. These layers of uncertainty make fakes hard to ferret out. “When you look at a negative result it could be many reasons,” says Zhu Weimin, senior vice-president of antibody technology for Abcam, which is headquartered in Cambridge, UK, but has a regional base in Shanghai. “The problem is serious.” The effects of this confusion and uncertainty are not limited to China. In 2012, for example, researchers in London and Białystok, Poland, reported using an antibody-based kit, called an ELISA, to detect a certain protein in the blood of people with chronic kidney disease1. But when kidney-disease specialist Herbert Lin of Massachusetts General Hospital in Boston purchased the same kit — branded as a product of USCN Life Science in Wuhan, China — and subjected it to rigorous testing, he found that it targeted another protein altogether2. The authors of the original study agreed it was now clear that the antibody was targeting the wrong protein2. “The fact that we did not receive replies from the manufacturers in relation to a couple of e-mails about their assay should perhaps have alerted us that something was not quite right,” they wrote. Cancer researcher Ioannis Prassas of Mount Sinai hospital in Toronto, Canada, had a similar experience with USCN-branded ELISA kits. Prassas says his team spent two years and some US$500,000 trying to identify the problem3. Chris Sun, who heads technology development at Cloud-Clone Corporation, the company in Wuhan that sells USCN products, says the company investigated the kit purchased by Prassas, but never identified the problem. It partially reimbursed Prassas. Sun denies that the company intentionally sold bad antibodies. “We have thousands of antibodies that we produce ourselves. We have no reason to use fake antibodies when we have the real ones,” she says, adding that they have no record of a complaint about the kit Lin found problems with. Most of USCN’s kits are sold through distributors, Sun adds, and the company has sometimes found counterfeits posing as USCN products. Estimating the scale of the issue is difficult, although some companies are trying. Late last year, Abcam tallied up roughly a year’s worth of concerns that it had received from scientists in China about the authenticity of Abcam-labelled products. After checking barcodes, lot numbers and purchase times, the company determined that counterfeit products were to blame for 42% of the hundreds of cases raised. What scientists are getting in the vials can vary. Sometimes, cheap, common antibodies are relabelled and sold as expensive, rare ones, says Jade Zhang, general manager of Abcam’s Shanghai branch. The counterfeiters will try to find an antibody of similar molecular weight so that scientists who do a quick test to verify the reagents won’t be alarmed. But in experiments, the antibodies will miss their targets. More common than antibody substitution is dilution. Counterfeiters buy authentic products from Chinese distributors or from overseas, then dilute one packet to make five, says Leng. “Customers get much weaker versions. Sometimes they can use them, sometimes not.” The counterfeiters “work hard to replicate our packaging, creating tubes and labels that resemble our own so closely that it can be difficult to tell the difference”, says Dong. “The counterfeiting problem seems to come from a small but active segment in the market.” And many of the players don’t realize they are involved. The Zhongguancun shop owner had no idea he was mixed up in illegal activity. “They are all part of a chain, but they are not evil,” Huang says. In 2015, Huang noticed a cleaner in his lab plucking empty bottles out of the rubbish and setting them aside. Confused, he asked why. “I warned her that she shouldn’t drink from them,” he says. She told Huang that someone was coming to buy them for 40 yuan (about US$5) a piece. It was another ‘a-ha’ moment. The bottles had originally contained fetal bovine serum (FBS), a ubiquitous cell-culture product derived from blood harvested at slaughterhouses. But a ban on imports of beef products from the United States, Australia and New Zealand, because of infectious diseases, had put a stranglehold on the supply of high-quality FBS. The price for reserves of serum from banned locations has doubled over the past few years, to about 10,000 yuan per bottle. Low-quality FBS from other sources costs about one-quarter as much as the banned imports, but it is a poor substitute. Thermo Fisher Scientific of Waltham, Massachusetts, which makes one of the most popular brands of serum, noticed the problem and created labels and bottles that are difficult to duplicate. That’s where the cleaner’s ‘recycling’ efforts came in. Counterfeiters can simply refill the bottles with low-quality FBS and charge premium prices. It’s hard to know how widespread the problem is, but Huang offers a back-of-the-envelope estimate: given the number of bottles consumed and discarded by major labs, the potential market for FBS counterfeiters in Beijing alone could be tens of millions of yuan per year. Counterfeiters are slippery, moving targets. In most cases, distributors will return payment or replace goods if a customer complains. That means there is no way for researchers to make a legal claim about their lost time and resources, which are the real cost. “Police will only look at direct loss — which is nothing,” says Leng. Companies lose revenue and may suffer dilution of their brand, but they also have little recourse. Abcam confronted some of the un-authorized distributors that were supplying apparent counterfeits of its products. The distributors said that they did not know where the antibodies had come from or how the problem occurred. Lawyers have advised against pursuing legal action, which would be costly and probably not get far. “If we shut one down, another would just pop up,” says Zhang. Leng agrees. He says the counterfeit companies, usually one or two people, “register a new company every year, then do the same business again”. And some scientists, although angry, don’t want to make a fuss, which would draw attention to the fact that they had been using counterfeits, says Zhang. The admission might raise questions about their previous research results. Huang himself doesn’t want to follow up with the cleaners, printers and others who are cogs in the counterfeiting machine, because they are just trying to earn a living. “If the printer makes 1,000 copies of a label, what’s wrong with that? The people who sterilize the bottles — they are probably doing a really good job,” he says. But scientists can take action in other ways. Huang centralized ordering for his institute’s most common reagents, so that for the majority of purchases he can ensure scientists are not being duped. And he set up a system that requires researchers to return an old FBS bottle before they can get a new one; the used bottles are destroyed. Others told Nature that after having been burnt, they pay higher prices to avoid third-party distributors. Luo Wei, a chemist at the Shenzhen Academy of Metrology and Quality Inspection, a third-party testing company, says that a starch-catalysing enzyme he bought had a suspicious smell and packaging. Its label said it came from Sigma-Aldrich of St Louis, Missouri, and the batch number and related information matched details of products on the company’s website. But Sigma confirmed that the white bottle it came in was not something it used for that product. It was counterfeit. Some reagent companies have also developed programmes to fight counterfeiters. Abcam, Cell Signaling Technology and Universal Bio have been teaching current and prospective customers how to spot fakes through seminars and online manuals. They’ve also opened complaint lines for those who suspect forgery. “The choice was to take legal action or educate our customers. We chose the latter,” says Zhang. Scientists can work together to spread awareness. Online chat rooms are full of advice, often based on experience, about how to avoid counterfeits. Some include blacklists of companies that have been found to deliver bad products. But for the many scientists in China outside major research hubs, there are fewer choices of distributor, and the word may not be reaching them, says Zhang. They may also have less funding, so price becomes a factor. They are more likely to be persuaded by claims that they are buying smuggled, high-quality goods at a low price. “We think most customers do not know they’ve been given a counterfeit,” says Zhang. Huang says the ultimate solution is to destroy the profitability of the enterprise. He helped to establish iBio, a 60% state-owned company that opened in December 2015 and brings customs and quarantine inspection under one roof, right on his institute’s campus. Huang, who doesn’t profit from the business, says most reagents are now available within ten days, compared with the month or more it might have taken before. Similar companies have been established in Shanghai and Suzhou. The speed puts Chinese scientists on an even footing internationally. “For each experiment there are one or two reagents that are a bottleneck,” Huang says. If Chinese scientists need months to get something that others get in days, “there’s no way Chinese science can compete with the outside world”, he says. It was that logic that in 2012 helped convince government officials to amend regulations, enabling expedited imports of biological reagents. But change has taken time. Huang is grateful for these improvements because they promise to make Chinese science more competitive. An added benefit might be the direct impacts on counterfeiters. “If you get rid of the customs burden, you destroy their profit margin,” Huang says. That’s better than tracking down culprits, to his mind. “If you cut out the source, you don’t have to go after them,” he says.

Liu X.-Q.,Zhengzhou University | Li Z.-Y.,Shenzhen Academy of Metrology and Quality Inspection | Yuan X.-J.,Zhengzhou University | Wu B.-L.,Zhengzhou University
Journal of Coordination Chemistry | Year: 2012

A purine-containing multifunctional ligand, 2-(6-oxo-6H-purin-1(9H)-yl) acetic acid (HL), and two new 2-D coordination polymers, [Co(L) 2(H 2O) 2] n2nH 2O (1) and [Ni(L) 2(H 2O) 2] n2nH 2O (2), were synthesized and characterized. Polymers 1 and 2 have isomorphous structures with (4,4)-connected topologies composed of left- and right-handed metal-organic helices sharing common metal centers. Two helical conformations in the same net are stabilized by strong π-π stacking interactions between purine groups. Through direct and water-mediated interlayer hydrogen-bond interactions those layers are assembled into stable 3-D supermolecules where slight differences in the strength of hydrogen bonds and coordination bonds result in their decomposition behaviors. © 2012 Taylor and Francis.

Chen Z.,Guilin University of Technology | Li Y.,Shenzhen Academy of Metrology and Quality Inspection | Lin S.,Hong Kong Baptist University | Wei M.,Guilin University of Technology | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2014

In this study, an easy and efficiency protein digestion method called continuous microwave-assisted protein digestion (cMAED) with immobilized enzyme was developed and applied for proteome analysis by LC-MSn. Continuous microwave power outputting was specially designed and applied. Trypsin and bromelain were immobilized onto magnetic micropheres. To evaluate the method of cMAED, bovine serum albumin (BSA) and protein extracted from ginkgo nuts were used as model and real protein sample to verify the digestion efficiency of cMAED. Several conditions including continuous microwave power, the ratio of immobilized trypsin/BSA were optimized according to the analysis of peptide fragments by Tricine SDS-PAGE and LC-MSn. Subsequently, the ginkgo protein was digested with the protocols of cMAED, MAED and conventional heating enzymatic digestion (HED) respectively and the LC-MSn profiles of the hydrolysate was compared. Results showed that cMAED combined with immobilized enzyme was a fast and efficient digestion method for protein digestion and microwave power tentatively affected the peptide producing. The cMAED method will be expanded for large-scale preparation of bioactive peptides and peptide analysis in biological and clinical research. © 2014 Elsevier Inc. All rights reserved.

Guan Y.,Tianjin University | Yin Y.,Shenzhen University | Li A.,Shenzhen Academy of Metrology and Quality Inspection | Liu X.,Shenzhen University | And 2 more authors.
Optics Letters | Year: 2014

An acoustic-optics heterodyne fringe interferometry coupled with a three-camera system is developed for dynamic 3D imaging. In this system, first-order beams with a slight frequency difference diffracted from two acousto-optic deflectors (AODs) form a beat intensity fringe pattern. Setting the frequency of the trigger signal for the CCD cameras into four times the beat frequency, four-step phase-shifting fringe patterns can be obtained, and the wrapped phase map (WPM) can be calculated. Under the epipolar constraint among three cameras, the homologous points can be determined unambiguously with the assistant of a WPM; thus the 3D shape can be reconstructed while skipping the phase unwrapping step. Experimental results are presented to validate this approach. © 2014 Optical Society of America.

Lu B.,Japan National Institute of Environmental Studies | Li Z.,Shenzhen Academy of Metrology and Quality Inspection | Kawamoto K.,Japan National Institute of Environmental Studies
Materials Research Bulletin | Year: 2013

The synthesis of mesoporous ceria (CeO2) without a template was studied in detail using NaOH and NH4OH solution. We first synthesized nanosized mesoporous CeO2 without a template by the direct hydrothermal synthesis method with NaOH. By using NaOH, mesoporous CeO 2 could be obtained without a template through the oxidation of Ce3+ ions, the hydrolysis of Ce4+ ions, polymerization and precipitation. Under appropriate synthesis conditions, the obtained mesoporous CeO2 had a high surface area, a narrow pore size distribution and an ordered structure with uniform mesopores. The surface area of the mesoporous CeO2 increased with increasing synthesis temperature. The NaOH concentration induced different behavior on the mesoporous CeO2 surface with and without a template. The mesoporous CeO2 had nanoarrays with uniform mesopores (intercrystalline voids). However, when NH4OH solution was used, the CeO2 had nanoarrays with a hierarchical pore network. The mesoporous CeO2 obtained without template had relatively high thermal stability that increased with increasing synthesis temperature. © 2013 Elsevier Ltd. All rights reserved.

Li Q.,Shenzhen Academy of Metrology and Quality Inspection | You J.,Hong Kong Polytechnic University | Zhang D.,Hong Kong Polytechnic University
Expert Systems with Applications | Year: 2012

Automated segmentation of blood vessels in retinal images can help ophthalmologists screen larger populations for vessel abnormalities. However, automated vessel extraction is difficult due to the fact that the width of retinal vessels can vary from very large to very small, and that the local contrast of vessels is unstable. Further, the small vessels are overwhelmed by Gaussian-like noises. Therefore the accurate segmentation and width estimation of small vessels are very challenging. In this paper, we propose a simple and efficient multiscale vessel extraction scheme by multiplying the responses of matched filters at three scales. Since the vessel structures will have relatively strong responses to the matched filters at different scales but the background noises will not, scale production could further enhance vessels while suppressing noise. After appropriate selection of scale parameters and appropriate normalization of filter responses, the filter responses are then extracted and fused in the scale production domain. The experimental results demonstrate that the proposed method works well for accurately segmenting vessels with good width estimation. © 2012 Elsevier Ltd. All rights reserved.

Liu Y.,Shenzhen Academy of Metrology and Quality Inspection | Yang Z.,Shenzhen Academy of Metrology and Quality Inspection
Advanced Materials Research | Year: 2013

In this paper, a research approaching on nano-TiO2 particles modified fabric functional enhancement is reported. The morphologies of the nano particles existing on the fabric surface were examined by scanning electron microscopy (SEM), which showed that the particle size is less than 100nm and almost no coacervation, and then water-repellent and oil-repellent performance of the modified fabric was measured by the contact angle method, and found they had the most desired water and oil release behaviors. In addition, the modified fabric showed excellent antibacterial effects according to FZ/T73023-2006 antibacterial standard, and the antibacterial efficiency was above 95%. Meanwhile, good durability of functional fabrics also observed which could endure 20 times washing at least. © (2013) Trans Tech Publications, Switzerland.

Wang X.,Shenzhen Academy of Metrology and Quality Inspection | Xing Y.-N.,Shenzhen Academy of Metrology and Quality Inspection | Chen Z.-Y.,Shenzhen Academy of Metrology and Quality Inspection | Lin H.-X.,Shenzhen Academy of Metrology and Quality Inspection
Journal of Chinese Mass Spectrometry Society | Year: 2013

A method for determinating trace migratory organo-tin in toys by high perform-ance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was developed. The organo-tin species dibutyltin(DBT), triphenyltin(TPhT), tributyltin (TBT) and dioctyltin(DOT) were separated on Waters Acquity UPLC HSS T3analysis column using the mobile phase of V(acetonitrile) : V(water) : V(acetic acid)=65:23:12, 0.1% triethylamine with pH 3.0.This method is quickly and high sensitivity. The detection limits are 0.08, 0.24, 0.14 and 0.65 μg/L for DBT, TPhT, TBT and DOT with injection volume of 50 μL. The recoveries are 80.7%-96.3% and 83.5%-100.4% for the spiked levels of 5 and 50 μg/L, and the RSDs are less than 47%, which meet the determination requirements. This method has been used to determine migratory organo-tin in accessible parts of toys, including coating, plastic, wood and textile.

Zhang S.,Shenzhen Academy of Metrology and Quality Inspection | Lai X.,Shenzhen Academy of Metrology and Quality Inspection | Yang G.,Shenzhen Academy of Metrology and Quality Inspection
Journal of Immunoassay and Immunochemistry | Year: 2013

A hen's egg is one of the most common causes of food allergy. The allergen quantitation in hot-processed food is always a difficult task, because the protein in these samples will be denatured, insoluble, and degraded. This article presents a competitive enzyme linked immunosorbent assay (ELISA) for the quantitation of ovalbumin in hot-processed food. Its recovery was improved nearly two times by the assay method as compared with previous sandwich ELISA. The heat and DL-Dithiothreitol treated ovalbumin was used as antigen for monoclonal antibody preparation. A smaller labeled antibody molecule, horseradish peroxidase (HRP) labeled Fab fragment, was used to replace IgG in ELISA for improving sensitivity and analytical speed of the method. A binding site protection procedure was developed for Fab fragment labeling with HRP, which prevented damage to the Fab binding site. The combination and separation steps were efficiently completed in an affinity spin column. Based on the optimized ELISA condition, the IC50 was 1.2 μg/mL and the coefficients of variation were less than 10%. Copyright © Taylor & Francis Group, LLC.

PubMed | Guilin University of Technology and Shenzhen Academy of Metrology and Quality Inspection
Type: | Journal: Food chemistry | Year: 2017

A novel continuous microwave-assisted enzymatic digestion (cMAED) method is proposed for the digestion of protein from Scomberomorus niphonius to obtain potential antioxidant peptides. In this study, bromelain was found to have a high capacity for the digestion of the Scomberomorus niphonius protein. The following cMAED conditions were investigated: protease species, microwave power, temperature, bromelain content, acidity of the substrate solution, and incubation time. At 400W, 40C, 1500Ug

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