有了这项技术，就能早早发现心脏病

心肌肌钙蛋白I和心肌肌钙蛋白T是确定心脏有无损伤的两种最有效的指标。80%的患者突发心脏病后，在被送到急救室两至三小时内，其血液中就会显现出心肌肌钙蛋白I水平增高的症状。

心肌肌钙蛋白是在心肌细胞损损伤或坏死时释放到血液中的，它也是我们在诊断严重心血管损伤时最敏感和最明确的一个指标。那么，它是否能作为预警此类损伤的一个早期指征呢？

正是在这种希望的推动下，医学界近年来围绕心肌肌钙蛋白和其他一系列具有高度敏感性的指征性蛋白展开了一系列创新研究。理想的目标是，如果我们能衡量正常人体内的微量心肌肌钙蛋白水平，那我们就能随着时间的推移来探测心肌肌钙蛋白水平的增量变化，从而提早对心衰或早期缺血性疾病进行预警，为患者争取宝贵的时间来延缓或逆转病情。

比如Quanterix公司就研制了一台名叫Simoa的高敏感性蛋白质检测仪，该公司CEO兼执行主席凯文·赫鲁索夫斯基指出：“如今，大多数能在血液中看到蛋白质的技术也能看到疾病指征，但它们看不到健康指征。而这种连续性是非常重要的，因为如果我们能够发现这些敏感蛋白水平出现了偏离基准水平的任何波动，而且能够在非常早期的时候就探测出来，我们就可以发现任何不健康的迹象。”

Simoa将50万个极小的连接抗体的“珠子”放入血液样本中。这些珠子会在血样中来回搅动，当它们碰到某种特定类型的蛋白质时，就会像魔术贴一样和它“粘”在一起。然后Simoa会投入第二种抗体，这种抗体在遇见特定的蛋白质（也就是上一轮产生的复合物）时会产生荧光。随后这些珠子会被滚动到一张索尼公司制造的光盘上，光盘上挖有212,000个小洞，大小只比珠子大一点。等珠子全部滚进洞里以后，激光摄像头会扫描每一个小洞，看珠子是否发出了荧光。哪怕只有一个小洞的一个珠子发出荧光，Simoa也能检测出来——也就是说，它能在血液的“海洋”中找到一个单一的靶蛋白，具有“大海捞针”的能力。

这项技术是在“夹心酶联免疫分析技术”（又称ELISA法）的基础上开发的。ELISA法早就不是什么新生事物了，早在半个多世纪前它就被发明了出来。赫鲁索夫斯基表示：“我们使用的还是非常传统的ELSIA测试法，只不过加入了一些‘电子把戏’。”然而这家位于马萨诸塞州列克星顿市的初创公司真正的厉害之处，在于以前做一次试验的时间，现在它能用来完成50万次测试。

这也是该公司的第一个目标。Quanterix公司创立于2007年，其创始人之一大卫·沃特也是知名基因测序公司Illumina的创始人。目前Quanterix公司正在与法国生物梅里埃（bioMérieux）公司合作开发诊断性测试技术，同时该公司也明智地没有干等FDA的批文——毕竟这个过程可能要耗上好几年的时间。该公司已经将这台标价16.5万美元的电冰箱大小的检测设备卖到了全球各地的制药公司、生物工程公司和大学实验室，好让全球各地的科学家来证明它的能力并发布结果。目前，外部科学家的试验已经证实，Simoa设备能够有效检测与脑震荡、脑创伤、阿尔茨海默症以及多种癌症、炎症的蛋白质指标。

这一战略与另一家血样检测公司Theranos的“黑箱操作”战略有很大差别（详见《华尔街日报》记者John Carreyrou的报道）。Quanterix是一家由贝恩资本、阿奇创投和旗舰创投等公司注资的私营公司，今年该公司的营收入预计将达到1900万美元——前提是如果不发生赫鲁索夫斯基所担忧的“监管和赔偿风险”。这也是该公司的第二个目标。

在数字医疗技术蓬勃发展的时代，第二个目标也可恰恰是创业者们可能更需要留心的。 （财富中文网）

作者：Clifton Leaf

译者：朴成奎

The troponin proteins—cardiac troponin I and T—are the best biomarkers we have for determining whether there’s been damage to the heart. As many as 80% of patients who have had a heart attack will show an elevated level of cardiac troponin I in their blood within two to three hours of visiting the emergency room.

But while troponin—which is released when heart cells are damaged or die—is the most sensitive and specific marker we have for serious cardiac injury, could it also offer an early warning sign of such injury?

That has been the hope driving innovation in a slew of new assays that aim to measure troponin and a host of other telltale proteins—more on those in a bit—with extraordinary sensitivity. Ideally, if we could measure minuscule amounts of troponin in healthy individuals, we could also detect the most incremental changes in its level over time—and warn of heart failure or early ischemic disease when there is still time enough to slow or reverse it.

“Today, most of the technologies that can see proteins in blood can see disease, but they can’t see health,” says Kevin Hrusovsky, CEO and executive chairman of Quanterix, which makes an über-sensitive protein-detection machine called Simoa. “And that continuum is very important because if we can see any migration from baseline, and be able to detect things very early, we can see any trend away from health.”

Simoa works by putting 500,000 little antibody-connected beads into a sample of blood. The beads slosh around in the blood and when they bump into a specific type of protein, they connect to it like Velcro. Then Simoa tosses in a second antibody—this one tied to a fluorescent light—which gloms on to any bound protein-antibody complex from the first round. The beads are then rolled onto a Sony disc that has 212,000 little holes on it. The beads fall into the wells, which are just a tiny bit bigger, “like a bingo ball sliding into a bingo tray,” says Hrusovsky. Eventually, a laser camera scans every single well to see whether or not there’s a light on a given bead. Simoa can detect just one light on one bead in one well—which is to say a single target protein in a relative ocean of blood.

The technology is based on what’s called a “sandwich ELISA,” which isn’t new at all. ELISA (enzyme-linked immunosorbent assay) has been around for more than half a century. “We are using a very traditional ELISA test and just putting some—I call it some digital trickery—onto it,” says Hrusovsky. But what the Lexington, Mass., company has really done is to figure out how to do 500,000 tests in the same time we used to do one.

That’s hack No. 1. And while Quanterix—which was cofounded in 2007 by David Walt, cofounder of gene-sequencing biggie Illumina—is (slowly) developing a diagnostic test with French firm bioMérieux, it has made the smart move not to wait around for FDA approval, a process that can take years. In the meantime, Quanterix has gotten its $165,000 fridge-sized machine into pharma, biotech, and university laboratories across the globe—essentially letting other scientists prove its mettle and publish the results. Outside scientists have already tested the company’s assays for detecting protein biomarkers associated with concussion and traumatic brain injury, Alzheimer’s disease, various cancers, and the inflammatory process that is likely involved in several pathologies.

The strategy, you may recall, is a far cry from the black-box approach of Theranos (see Carreyrou, John, WSJ). This year, the privately held Quanterix, which is backed by Bain Capital Ventures, ARCH Venture Partners, and Flagship Ventures, among others, expects to pull in $19 million in revenue—without what Hrusovsky calls “regulatory or reimbursement risk.” That’s hack No. 2.

In the burgeoning age of digital health, it’s that second hack that entrepreneurs may want to take heed of.