ABI推出新型質譜，欲圖扭轉質譜業務再上頂峰

2008年10月16日

經過幾個月的猜測和預期，美國ABI公司和它的質譜合資伙伴MDS于上周推出了兩款新型質譜系統，從而結束了ABI公司在歷經18個月技術創新乏力而導致的質譜業績下滑局面。

這兩臺新型儀器分別是5500型三重四級桿質譜儀和5500型Qtrap線性離子阱質譜儀，根據AB和MDS的說法，這兩臺儀器代表了最先進的質譜技術。

新品的發布同時標志了ABI公司超過三年來最重大的質譜發布事件。在新產品的市場驅動下，新產品的發布對在質譜產業上已經呈下滑趨勢的ABI公司來說，起到了強有力的推動作用。

在網上宣布推出后，ABI公司和MDS官方聲明，建立在完全重新設計的平臺上的新型質譜儀將成為“下一代”的系統。

MDS的分析技術總裁Andy Boorn指出，要創新而不是在原有的儀器上進行改動，5500型三重四級桿質譜儀和5500型Qtrap線性離子阱質譜儀可以被稱為是真正的創新。

雖然兩家公司還缺乏具體的數據來支持他們的聲明，ABI公司蛋白質和小分子部門經理Laura Lauman指出：“下一代的質譜系統在為我們的客戶提供創新性的解決方案方面，樹立了ABI和MDS公司合作的一個重要里程碑。伴隨新儀器的推出，我們再次為質譜的性能建立了新的標準。”

5500型三重四極桿質譜儀

 在5500型三重四極桿質譜儀中，采用了新型的脈沖計數探測器AcQuRate，它能夠“有效地”檢測離子來增加定量的準確度和精密度。根據ABI/MDS的說法，5500比其它質譜儀的靈敏度至少高5倍。

Boorn雖然沒有提供細節，但他指出彎曲180度的線性加速碰撞池（Qurved LINAC Collision Cell）和eQ 電子學技術，提高了分析速度和掃描速度。

他補充說道：“該儀器可以在復雜樣品的低濃度下檢測出更多的目標物質，可以從一次簡單的實驗中獲得大量的數據，并具有更高的定量準確性和更低的檢測限。”他們沒有提供具體的數字。

5500型Qtrap質譜儀

同時，5500型Qtrap線性離子阱質譜儀也具有5500型三重四極桿質譜儀的特點，并結合了一款新的線性加速的離子阱（Linear Accelerator Trap）技術，“該技術是為建立一種在線性離子阱模式下定性的新標準而專門設計的。”公司的發言人在一份聲明中說。

這臺儀器中的另一項新型的技術是三重阱掃描（Triple Trap Scanning），Boorn說到：“該技術可以使科學家們，從靈敏、確定性非常高的三重四極掃描模式，在不到1毫秒的時間里切換到高靈敏的全掃描離子阱模式”，這是在其他儀器上無法實現的數據驅動（data-driven）的采集流程。

在蛋白質組學研究中，QTrap 5500 使研究者們定量和確認“大量的蛋白質和肽段，并具有比其它任何已有系統更高的靈敏度、重現性、精密度。”Lauman指出，雖然也沒有給出具體數字。

ABI公司的蛋白組和小分子學新技術業務部的經理Dominic Gostick指出，蛋白質組研究人員目前關注的生物標志物發現需要更多的靶向方法，而Qtrap 5500可以賦予研究者更強的能力去發現相關的生物標志物。
“人們現在已經發現了相當數量的潛在的生物標志物，但是現在對他們來說未必有用。”他說，“我認為在小分子和蛋白質組的研究中，該技術都會提供新的能力，因為該儀器可以對這些推測的生物標志物進行核查和驗證。”

“而且對人們來說確實是非常迫切的需要，他們需要導向目標追蹤，把真正臨床相關的生物標志物和只是實驗的人工品區分開來。”

 

--------------------------------------------------------------------------------
貫徹其一致性是絕對必須的，換種說法就是保持它的市場領先地位。
--------------------------------------------------------------------------------

在多倫多Mt. Sinai醫院Samuel Lunenfeld研究所的研究人員，使用了早期階段的儀器。對他們而言，具有更高MRM靈敏度和更快速度的QTrap 5500是非常有誘惑力的。

該研究所的質譜專家Lorne Taylor說到：“在樣品相當復雜的情況下，我們經常發現MRM自己使研究人員進入誤區，常得到一些假陽性的信息”，“QTrap 5500可在第一毫秒進行MRM的測量，接下來在第二毫秒進行MS/MS的工作，我們擁有驚人的速度，我們可以確認我們測量的結果是真實的。”

此外，每個時間單元具有更快的分析速度可以使研究人員在實驗中嵌入更多的控制。

 “我們把這些在復雜基體中的蛋白質用胰蛋白酶酶解，我們通過測量它們的碎片（肽段），然后從中推斷生物學性質”，Taylor說到，“從多肽回到蛋白質，有大量活動的部分/步驟，所以在這里嵌入控制是至關重要的，使用這臺新型儀器，可以更靈敏地獲取更多信息，使我們不僅能夠尋找到以前找不到的物質，并且還能控制他們。”

這種新型的平臺非常符合ABI公司的試劑和工作流程技術，其中包括用于目標物定量的蛋白質組學軟件MRMPiolot和MultiQuant，和mTRAQ試劑。

這套新系統定價為$450,000 ～ $490,000。Lauman說，ABI公司已經有了客戶訂單并且該儀器已經在運輸過程中。

貫徹其一致性

兩款新儀器珊珊來遲，比ABI公司質譜業務的估計晚了幾個月，ABI官方承諾該儀器會在年底打入市場。盡管ABI公司仍被認為是業界的領先者，但是至少在人們的感覺中，MDS分支已經作為技術的革新者開始沾沾自喜了。

ABI公司最后推出的一款重要的質譜儀器是測量小分子的API 5000，于2005年1月推出，接下來四個月后推出了型號為4800的MALDI TOF/TOF儀器，用于研究蛋白質生物標志物。

此后ABI公司推出的新型系統都只是在原有平臺上進行改善，并沒有革命性的創新。

與此同時，競爭對手例如Thermo Fisher 和Waters公司利用ABI公司的技術停滯，分別推出了Orbitrap和Synapt兩款新型的儀器，被他們推廣為變革性的技術。同時，Agilent科技，一度在質譜界被看作是邊緣玩家的安捷倫科技，也擴大了其在市場上的占有位置。

來自Wall Street Access研究投資公司的分析師Peter McDonald指出，上周的新品發布是ABI公司擊退其他競爭對手的重要一步。“貫徹其一致性是絕對必須的，也就是說，保持他們在市場上的領導地位”，他說道：“我不認為新品的發布是一個戲劇性的重塑事件，但它確實攪起了漣漪，可能迫使購買者為了這個新型的系統而推遲購買時間。”

他還指出：“總體來說，這是件好事，可以繼續推動和擴張整個市場潛力。”

Lauman認為5500三重四極 和 QTrap 5500的研發周期比ABI公司自己預想的要長，因為融入到儀器設計中的創新，“使我們能夠非常迅速地建立起衍生平臺。”

Boorn指出這兩臺儀器的推出僅僅代表了MDS在這25年里在LC-MS領域里的第三次改革，并在這個領域里創建了一個新的平臺。

“我們的研究人員和工程師隊伍對儀器上的每一個部件都進行了檢查，基本上全部更換了它們，然后在和我們全球客戶非常緊湊的調查反饋循環中，不斷詢問他們是否真正的解決了他們的問題。”

許多來自客戶的問題和要求是“非常難以解決的”，他補充說，包括對更小尺寸儀器的需求。這臺新型的系統比以往的系統尺寸要小44%。

Boorn指出，加快該系統的檢測速度是一項非常“具有挑戰性的研發任務，需要完全重新設計電子學部分，發明新型掃描模式，設計離子光學，才能確實、確實、確實得達到快速掃描的要求。”

對于ABI公司來說，該技術的推出恰好是在該公司的質譜業務處在一個非常極有挑戰性的時期。盡管沒有給出具體的數據，但是ABI的競爭對手們已經在前幾個季度的質譜銷售領域里茁壯成長。ABI公司的質譜銷售業績比去年同期相比已經成下降趨勢。在連續的六個季度中，質譜的銷售業績連年下滑，已經從14％（截止到2006年12月31日的三個月）到不到1%（截止到2008年3月31日的季度）

對于截止到6月30日的這三個月里，最近的一個季度銷售業績顯示比同期相比上升了4%。該公司將在10月22日宣布2009第二季度的銷售業績。

ABI公司的前母公司Applera公司（不久前被分為ABI和Celera兩個獨立的公司）的前首席執行官Tony White，和ABI公司的總裁兼首席運營官Mark Stevenson同樣認為，延遲新型儀器的推出，已經削弱了該公司的銷售業績。

當在夏季ABI公司和Invitrogen公司宣布以67億美元兼并時，立即引起ABI公司可能出售質譜業務的猜測，因為它沒有納入合并后的公司的商業模式。雖然ABI和Invitrogen公司的官員堅持說他們的每一個意圖都是為了保持質譜業務，但是MDS公司的首席執行官Stephen DeFalco在近期的一個分析會議上含糊地提出了一個觀點，MDS公司正與ABI公司協商合資協議，不排除從他的合作伙伴那里收購質譜業務。
然而，ABI和Invitrogen公司最近聲明，質譜部門將成為合并后公司四大分支中的一個。上周Stevenson稱這次發布為：“展現了質譜市場一個令人興奮的時期”，該儀器將會繼續被應用于更多的應用領域，發布新品“表明了我們將會繼續致力于這一重要市場”。

華爾街分析師McDonald指出，隨著ABI / Invitrogen公司預計在11月完成合并，新型質譜儀的發布和下一代測序平臺SOLiD 3.0 的發布，說明了ABI公司依舊保持著在技術研發領域的進取心。

他還說到：“我認為這是一個好的跡象，那就是合并本身并沒有削弱他們開發新產品的勢頭，這是一個好信號，一旦交易完成，每個業務都會被整合得相當好。”

 

參考英文原文：

ABI Launches New Mass Specs as It Tries  To Turn MS Biz Around and Stay On Top

[October 16, 2008]

By Tony Fong

After months of hints and wide anticipation, Applied Biosystems and its MS joint-venture partner MDS last week launched two mass spectrometry systems, putting an end to a technology drought that dragged down ABI’s mass spec business for the past 18 months.
 
The two new tools, the AB Sciex Triple Quad 5500 and the AB Sciex QTrap 5500, represent the most advanced mass specs ever, according to the partners.
 
The announcement also happens to mark the firms’ most significant mass-spec introduction in more than three years. In a segment driven by new products, the launches may provide the spark needed to revive ABI’s mass spec business, which has been on the decline recently.
 
In a webcast announcing the introductions, ABI and MDS officials said that the tools are “next-generation” systems built on new platforms that were designed from the ground up.
 
To wit, rather than replacing pre-existing instruments, the Triple Quad 5500 and QTrap 5500 are “a true expansion” of the companies’ portfolio, said Andy Boorn, president of MDS Analytical Technologies, the division within MDS that develops and manufactures mass specs.
 
The companies were short on specific data backing up their claims but according to Laura Lauman, president of ABI’s proteomics and small-molecules division, “These next-generation mass-spec systems represent a significant milestone for the joint venture and Applied Biosystems in providing innovative solutions for our customers. … With this launch we are once again setting new standards for performance in mass spectrometry.”
 
In the Triple Quad 5500 instrument a new pulse-counting detector, AcQuRate, “effectively” detects ions to increase quantitative accuracy and precision. Compared to other triple quads, the 5500 is up to five times more sensitive, according to ABI/MDS.
 
New components such as the Qurved LINAC Collision Cell and eQ Electronics increase analysis speed and scanning speeds, according to Boorn, though he did not provide details.
 
The instrument, he added, enables researchers to ID “the greatest number of target analytes at the lowest concentrations in complex samples … [and] enables a great amount of data to be acquired from a single experiment [resulting in] greater quantitative accuracy and lower limits of detection.”
 
No specific figures were provided.
 
Meanwhile, the QTrap 5500 takes the features of the Triple Quad 5500 and combines them with a new Linear Accelerator Trap technology, which is “designed to set a new standard in the linear ion trap-based qualitative mode,” the companies said in a statement.
 
Another new technology built into the machine, Triple Trap Scanning, allows scientists to migrate from “sensitive, very specific triple quadrupole scan model to highly sensitive full scan ion trap mode in less than 1 millisecond,” Boorn said, enabling workflow data-driven acquisition that cannot be achieved on other systems.
 
For proteomics research, the QTrap 5500 allows researchers to quantify and confirm an “increasing number of proteins and peptides with greater sensitivity, reproducibility, and precision than any other available system,” said Lauman, though no specific figures were given.
 
Dominic Gostick, director of new technology business for proteomics and small molecules at ABI, said that as proteomics takes on an increasingly targeted approach to biomarker discovery, the new instruments will give researchers greater capability to find relevant biomarkers.
 
“People have now discovered fairly long lists of potential biomarkers, and that’s not actually proving to be that useful for them today,” he said. “And I think this technology in both small molecules and proteomics offers a whole new capability because they can take these lists of putative biomarkers and shift those into verification [and] validation.
 
“And that really is compelling to people because they need to home in on what are the clinically relevant biomarkers against what has just been an artifact of the experimentation,” he said.
 

--------------------------------------------------------------------------------
“It’s definitely necessary to keep them in line with the herd, so to speak, and maintain their market leadership position.”
--------------------------------------------------------------------------------
 
Researchers at the Samuel Lunenfeld Research Institute of Mt. Sinai Hospital in Toronto were allowed access to an early iteration of the instruments. For them the higher MRM sensitivity and faster speed of the QTrap 5500 is especially appealing. 
 
“Even with … moderately complex samples, we have noticed routinely [that] MRM by itself can lead you astray. It can give a lot of false positive information,” said Lorne Taylor, mass spectrometry specialist at the institute. With the QTrap 5500, “we can do an MRM measurement in 1 millisecond in this new box, then we can flip and do an MS/MS in 2 milliseconds, so we have incredible speed. … We want to be very, very sure that we’re measuring what we think we’re measuring.”
 
In addition, the faster speeds allow for more assays per time unit which in turn will allow researchers to embed controls into the experiments.
 
“We take these proteins in complexes and we rip them apart to pieces with trypsin. We measure the pieces and then we infer biology back from that,” Taylor said. “There [are] a lot of [moving parts] going from peptide back to protein. Embedded controls are crucial here, so with the ability of the new machine to do so much more at a higher sensitivity allows us to be able to not only look for things that we couldn’t before, but to control for them.”
 
The new platforms are compatible with ABI’s reagents and workflow technologies including MRMPiolot and MultiQuant software for targeted quantitative proteomics and mTRAQ reagents.
 
The systems sell for between $450,000 and $490,000. ABI has orders for them already, Lauman said, and the company is shipping the instruments now.
 
‘In Line with the Herd’
 
The launch of the instruments comes after months of speculation about ABI’s mass-spec business, and promises from company officials that major new instruments would be hitting the market by the end of the year. While ABI is still regarded as the industry leader, there was at least the perception that it, and by extension MDS, was becoming complacent as a technology innovator.
 
The last major mass spec introduction from ABI was in 2005 when it launched the API 5000 for small-molecule analysis in January, followed up four months later with the launch of the 4800 MALDI TOF/TOF for protein biomarker study.
 
Since then ABI has put out new systems, but rather than being revolutionary the new introductions were seen as incremental improvements on existing platforms.
 
In the meantime, competitors such as Thermo Fisher Scientific and Waters took advantage of ABI’s technology lull by launching new Orbitrap and Synapt instruments, respectively, which they pushed as transformative technology. Simultaneously, Agilent Technologies, once seen as a marginal player in the mass-spec space, broadened its presence in the market. 
 
Peter McDonald, an analyst at research and investment firm Wall Street Access, called last week’s launches an important step for ABI to beat back the competition. “It’s definitely necessary to keep them in line with the herd, so to speak, and maintain their market leadership position,” he said. “I don’t know that it’s a dramatic reshaping of the landscape but it definitely adds another wrinkle and it may force people to … delay purchases a little bit longer if they need to take a look at the new systems.
 
“Overall, it’s probably good for the space as it continues to drive uptake and expand the whole market potential for this,” he said.
 
Lauman acknowledged that the development cycle for the Triple Quad 5500 and QTrap 5500 took longer than ABI had anticipated but because of the innovations incorporated into the design of the instruments “allows us to create derivative platforms very rapidly.”
 
Boorn said that the two launches represent only the third time in the 25 years that MDS has been in the LC-MS business that it has created a new platform from the ground up.
 
“Our research and engineering team examined every component in the system and basically changed them all, and then in very tight iterative loops with our customers around the world, asked them if this was truly going to address their questions,” he said.
 
Some of the questions and requests coming from customers “were very difficult to solve,” he added, including the need for smaller instruments. The new systems have a 44-percent smaller footprint than previous systems.
 
In addition, increasing the speed of the systems was a very “challenging part of the development task and required the complete redesign of the electronics and the invention of new scanning modes and designs of the ion optics [to] address those really, really, really fast scanning requirements,” Boorn said.
 
For ABI, the launches come at an especially challenging time for its mass-spec business. While its competitors have been citing healthy growth in their mass-spec sales in recent quarters — albeit without giving specific numbers — ABI’s year-over-year mass-spec sales have been trending down. For six straight quarters, its mass-spec sales have steadily declined year-over-year from 14 percent in the three months ended Dec. 31, 2006, to less than 1 percent for the quarter ended March 31, 2008.
 
For the three months ended June 30, the most recent quarter for which figures are available, sales of ABI’s mass specs rose 4 percent year-over-year. The company will release its fiscal 2009 second-quarter results on Oct. 22.
 
Both Tony White, the former CEO of Applera, ABI’s parent company before it split ABI and Celera into two independent firms, and Mark Stevenson, president and COO of ABI, have acknowledged that the delay in new instrument platforms has put a dent in the company’s mass-spec sales [See PM 01/31/08 and 07/31/08].
 
When ABI and Invitrogen announced its $6.7 billion merger during the summer, speculation immediately arose that ABI’s mass spec business could be sold because it didn’t fit into the combined company’s business model [See PM 06/19/08]. While ABI and Invitrogen officials have steadfastly said that they have every intention of keeping the mass spec business, MDS’ CEO Stephen DeFalco, sounded a more equivocal note at a recent analyst conference, saying the company was evaluating its joint-venture agreement with ABI and had not ruled out buying the mass spec business from its partner [See PM 09/25/08].
 
ABI and Invitrogen, however, recently announced that mass spectrometry will make up one of four divisions in the newly combined company. Last week Stevenson called this “a very exciting time for the mass spectrometry market,” as uses for the instruments continue to evolve for a growing number of applications. The launch of the systems “demonstrates our continued commitment to this important market,” he said.
 
As the ABI/Invitrogen merger closes in on an anticipated November closing, the mass spec launch as well as the introduction of its SOLiD 3.0 next-generation sequencing platform indicates that ABI remains aggressive about technology development, said McDonald, the Wall Street analyst.
 
“I think it’s a good indication that the merger itself is not distracting them from their new product momentum, which is a good sign for once the deal closes that each of these business can be integrated pretty well,” he said.

 

相關鏈接：

5500介紹

突破與超越——AB公司推出QTrap 5500和三重四極5500型質譜儀