The current situation and problems of the upstream and downstream development of the gene sequencing industry chain in China.

The milestone sediton of the development of the gene sequencing industry, it is difficult to bypass the ordinary single customs clearance nine years ago in Shenzhen: the product involved in 128 (sets) high-throughput sequencer HiSeq2000, the buyer is China's Huada Gene Company, the seller of the United States Illumina Company.
" is an important capital for its (China University) development.
", as investment scholar Yang Baozhong wrote in an analysis, most online articles selectively define the effect of the order on a trading side.
" has gained a foothold in China's sequencing market, a deal that is also crucial for Illumina. Wang Liang, founder of
" Gene Hui, is one of a few more comprehensive industry researchers, he said in an interview with Science and Technology Daily on April 13, high-throughput sequencing industrialization began in 2007, the market in 2010 has not yet matured, follow-up gene sequencing business model is even more uncertain.
the industry was unstable, Illumina gained the capital and market awareness of the development from this big single.
until January 2014, the former State Food and Drug Administration issued a notice of product definition, the gene analyzer as a three-type medical device management, the downstream industry development door has been opened.
to this single transaction as a starting point, China's gene sequencing industry in recent years has developed rapidly, the life of the "day book" reading and reading derived from a variety of business models.
and when people review and examine China's high-tech industry because of the SMIC incident, it is found that the gene sequencing industry and the information industry seem to have a similar structure - upstream is held by a few foreign enterprises, China's capital and enterprises are still concentrated in the middle and lower reaches of the industry.
sequencers are the decisive devices in the gene detection and gene editing and gene synthesis industries, and are similar to those in the communications industry.
time to ponder: What exactly supports the development of China's gene sequencing industry? What has China Core experienced? What stage is it now? After the difficult production of the sequencer in 2013, from time to time came the news that the sequencer is about to mass production.
The Beijing News, entitled "Zixin PharmaceuticalGene-Drug Gene Sequencing Device Mass Production Cloud", wrote: "Three years have not yet landed;
this probably sums up the dilemma of most attempted sequencing device research and development and production enterprises.
domestic enterprises test water sequencer production, is "knowing that there are tigers in favor of the tiger mountain line." One of the reasons
is that illumina unilaterally asked for a price increase around 2013.
analysis shows that Illumina's price increases have reduced Huada's profitby by 10%.
industry is aware of the crisis of "neck-and-neck".
, the desire for technological autonomy is as strong as it is today, but "Tiger Mountain" is not said on the line.
sequencer is an upstream platform for the sequencing industry.
platform means that the "instrument" does not refer to the narrow meaning of "instrument equipment", but covers instruments, reagents and consumables, as well as software development and other aspects.
" production of sequencers requires a combination of mechanical, electronic, chemical, physics, molecular biology, information software and other disciplines. Lu Zuhong, a professor at The
" Southeast University, said the high-end equipment manufacturing industry also seemed difficult to cover the production process of the sequencer.
According to the definition that the third industrial revolution is involving information technology, new energy technology, new materials technology, biotechnology, space technology and so on, the research and development of sequencers requires the integration of technologies that have emerged in all third industrial revolutions, except for new energy and space technology.
, "cross-border" is the basis of the sequencer, "precision" is the "life gate" of the sequencer.
genetic sequencing is like "ant moving mountain", when moving "every grain of sand" to be aligned to the position.
sequencing, the microliter solution contains 1,000 single-stranded molecules of DNA to be tested, and different individual bases "find tissue" (synthetic upper chains) emit different fluorescences to detect fluorescent colors that can read DNA.
However, the synthesis of 1,000 molecules per cell is difficult to synchronize," when the molecule is synthesized to 99, the molecule may have synthesized to 101, so that the captured fluorescent wavelengths will be disturbed.
", Lu Zuhong said, to measure, it is necessary to reduce interference, improve the accuracy of sequencing.
the high technical threshold, high capital investment, research and development cycle is also the difficulty of the industrialization of the sequencer.
" a prototype in the laboratory to come out, need more than 1 billion yuan of capital investment, research and development cycle for decades or so.
" Wang Liang said that at present, China has nearly ten or so in the promotion of research and development.
the new technology on the top of the "difficult" so, in the development of the upstream industry of gene sequencing, the new technology developed from scratch will not have a subversive effect? "I would have been a little more optimistic if I had come out a few years ago when Illumina wasn't in the climate.
", Lu Zuhong recognized China's technological innovation at the laboratory level, but from industrialization to mass production, to the market, but is another "story."
in addition to the sequencing instrument itself will compete with monopoly natural, in the matching supply will still encounter another "card neck."
" Our country has been pushed out by large international companies, such as through reagents, enzymes, etc., in supply.
," Lu said.
new technology to stand, in addition to giving up years of market share, but also to continue to challenge the "oligarchs" and remove the market acceptance of this new technical position of another obstacle.
"New technology, even if good, let the market 'abandon the old and new' resistance is also very large.
," Lu said.
" sequencer is like an operating system, to be able to carry, compatible with different 'APPS' to be widely used.
"HuaDa Zhi made COO Jiang Hui such analogy, a new instrument if the use of a brand-new system, it is like skipping the "Android" "IOS" system, their own "start a new stove", to obtain the entire market cooperation is very difficult.
such a "difficult situation" for China's industry is unique.
for example, in the field of medical imaging, GE, Hitachi, Philips in China's Three-A Hospital for many years, the industry has even reached a consensus: do not change the track (the principle of transformation), China's medical imaging enterprises have little possibility to break the monopoly.
What are the opportunities for the gene sequencing industry? Is it waiting for the original innovation, changing the track, or the introduction of the label, the joint venture development? Key core technologies are in the hands of others, the biological industry in the field of instrument manufacturing experts are no strangers, according to statistics, gene sequencer giant Illumina in the field of gene sequencer core technology patents up to five figures.
experts say its patent protection has been systematically and densely surrounded by core technology as a "barrel of iron."
"the key core technology is the national heavy instrument" "cultivate a number of cutting-edge scientific instrumentmanufacturing enterprises" ... At the second meeting of the Central Finance Committee in July 2018, General Secretary Xi put forward higher requirements and goals for the high-precision instrument industry. How do
highlight the re-enactment? Even if the technology breaks the ice, still need mature products, improve market share, out of the core technology of the "difficult" sequencing upstream industry and how to deal with the development of "bewilderment"? Independent ice-breaking is only the starting point of 2012, has been buying Illumina instrumentHuaDa gene suddenly found that reagent supplies price increased several times, the new instrument is difficult to buy, the old instrument is no longer repaired.
the other side even to China University's development "finger-pointing", "Huada hope to the genome program to obtain the technology and results of the clinical transformation into medicine, and to promote clinical need to obtain the equipment-owned enterprises license and support."
" Huada Zhi-chi COO Jiang Hui said, the other side does not support Huada.
until 2013, things turned around.
complete Genomics, the third-largest company in the U.S. in genetic sequencing, has a sales plan, and Huada decided to seize the opportunity to address patent issues through acquisitions and to achieve autonomy and control of core tool capabilities. "We're glad we made the decision to close the acquisition,"
. Zhu Yanmei, executive vice president of
huada group, said the acquisition not only changed the situation of Huada's hostage-taking, but also allowed China's high-throughput sequencer core technology to be realized from scratch.
"At that time we got a prototype weighing 2 tons, is a veritable 'black tower'."
" Jiang Hui recalled, in order to allow the prototype to be mass-produced, the team did a lot of work.
two years later, China's own instruments appeared on the market.
later, specializing in the research and development of the sequencer of Hua Dazhi caused the establishment.
October 25, 2018, Huada Zhizhi released the T7, the daily output data of 6Tb, the fastest output data sequencer.
seize the opportunity to break the ice, just the starting point.
" gene sequencing industry has upstream and downstream chains, in addition to the production of high-precision sequencers, but also equipped with effective kits, as well as complete sets of solutions. jiang Hui said
that Huada followed up the development of nanosphere technology, can achieve the original "photocopy" before sequencing amplification, find a thousand pick sequencing enzymes, so that biochemical reaction time can be shortened to 1 minute..." with technological innovation to challenge the 'oligarch', improve the sequencing capabilities and standards.
" Jiang Hui said that from the enterprise itself, the practice of "inner work" is to promote the establishment of a mature genetic detection service network, docking downstream sequencing and scene landing enterprises premise.
2018, the media published the industrial layout map shows that in the upstream instruments, reagents, software have three aspects of research and development and production capacity, Illumina and Huada are listed.
Huada has become a Chinese company that has achieved mass production of sequencers.
this shift has been recognised by the international market, says Mathias Uhlen, a member of the Royal Swedish Academy of Engineering: "The quality of the data produced in the project is very satisfactory, and in fact it is the best data we have ever seen."
", China ElectronicS Technology Group, the 41st Institute of the chief scientist NianFushun previously in an interview with the People's Daily, said: It is expected that China's scientific instruments in the next few years will enter an important stage of promotion and application, will ease China's dependence on foreign high-end scientific research instruments.
related industry insiders said that there are also many enterprises are investigating or promoting the production of a new generation of gene sequencers, it is estimated that there are nearly ten domestic enterprises in the test water high flux after the update disnewe generation of technology.
out of the promotion and application of the "weird circle" in the breakthrough "card neck" technology, the Chinese Academy of Sciences academician Yan Guangnan has pointed out that when the product formed by autonomous technology has been "unavailable" to "available", need to be in the application of "training", in order to be from "available" to "good use" development.
important stage of promotion and application is coming, the market doesn't seem ready: euphoric for technological innovation, while experimenting with new products.
the most chilling is the "three nos" attitude of the user: not accepting, not caring, not trying.
new technology, if not used in five or six years, foreign new iterations, and new technologies will fall behind.
to this, some industry experts said, on the one hand, the research and development side should have the spirit of artisans, the instrument engineering, reliability research should continue to strengthen;
in fact, the government has introduced a number of incentives to promote the landing of the first set of major technical equipment, such as the first (set) of major technical equipment belonging to the domestic market price of no more than 60% of the cap subsidy, some local governments have also introduced a market-oriented insurance system, and for enterprises to subsidize insurance costs.
", in theory, the procurement of equipment supported by state funds should adhere to the principle of 'domestic production not import', but in practice, the premise of whether there is domestic judgment is difficult, even delicate.
," said one expert, who asked not to be named.
the application of domestic instruments into a "weird circle" - difficult to promote, few users, research and development enterprises difficult to improve according to feedback, so that products can not catch up with the world's highest quality, product quality gap has caused the application of the difficult situation.
's technological innovation "training ground" seems to be blocked by a stubborn bias.
the belief that "imports are well used" also brings inertia.
Huada Gene in the bidding of scientific research projects have also encountered similar rejection, "there are colleges and universities, in setting the threshold to increase the limit, there is a clear direction and exclusivity, so that only certain enterprises can enter the bidding process."
," Zhu said.
the opening of the "training ground" will be beneficial to the establishment of the whole sequencing industry ecology, and full competition is the basis of healthy ecology.
" has China's independent instruments, can establish a healthy development of the sequencing ecology.
" Zhu Yanmei hopes that for the sequencing industry, nearly 90% of the sequencing data from foreign monopolies output can be changed.
Source: Science Daily.