為人類健康服務(wù)的光學(xué)技術(shù)

文 / 儲(chǔ)扎克（Zachary J. Smith，美） 譯 / 楊云舟

什么是科學(xué)研究？科學(xué)研究有其遵循的一定流程。首先，我們需要提出一個(gè)想法來(lái)構(gòu)成初步的假設(shè)；其次，我們需要制定一個(gè)研究方案來(lái)驗(yàn)證假設(shè)，精心設(shè)計(jì)并開(kāi)展試驗(yàn)；最后，通過(guò)分析試驗(yàn)得出的數(shù)據(jù)，我們能夠揭示最初的假設(shè)是否正確。如果假設(shè)錯(cuò)誤，我們就必須回到第一步，修改假設(shè)，進(jìn)行“再研究”，再將流程循環(huán)到底。其實(shí)，科學(xué)研究的方法可以越過(guò)純粹科學(xué)的邊界，應(yīng)用到生活中的許多方面。它實(shí)際上是幫助我們應(yīng)對(duì)和解決生活難題的一個(gè)視角。正因如此，我們發(fā)現(xiàn)，有著嚴(yán)謹(jǐn)誠(chéng)實(shí)的態(tài)度并且秉持以公眾利益為重的科學(xué)，掌握著世間所有問(wèn)題的答案，也擁有能夠改變世界的力量。

那做科學(xué)家又是什么樣的呢？他是一個(gè)像謝爾頓·庫(kù)珀（美劇《生活大爆炸》中主角之一）那樣的人，還是一個(gè)整天做實(shí)驗(yàn)的實(shí)驗(yàn)室小白鼠？其實(shí)，醫(yī)院里的醫(yī)生也是科學(xué)家，他們采集樣本，進(jìn)行測(cè)試，以驗(yàn)證他們的假設(shè)——醫(yī)療診斷——是否正確。某些政府領(lǐng)導(dǎo)人也是科學(xué)家，他們?cè)诓煌芯款I(lǐng)域都有著各自的科研成就，科學(xué)訓(xùn)練幫助他們更好地領(lǐng)導(dǎo)、治理我們的社會(huì)。

我和我的研究團(tuán)隊(duì)將目光定格在了一個(gè)特殊的領(lǐng)域：生物醫(yī)學(xué)光子學(xué)。這一方向研究的基本思路是利用光子的力量來(lái)解決生物和醫(yī)藥領(lǐng)域的核心問(wèn)題。目前，我們的研究主要有3個(gè)分支：無(wú)標(biāo)記顯微技術(shù)、納米尺度拉曼光譜和成像，以及資源匱乏地區(qū)專用的醫(yī)療診斷技術(shù)。

What is scientific research? It has its own internal cycle where the first step is to bring forward an idea, which will constitute your hypothesis. To examine this hypothesis you will need to come up with a research protocol and carry out well-designed experiments. Experiments produce data to be analyzed, thus revealing if the initial hypothesis is correct or not. And if not, we must return to the first step, revise our hypothesis, and “reresearch” until the whole cycle is completed. This method of scientific research can also be applied to many other aspects in life beyond the boundaries of strict science. The scientific method is actually a perspective through which to look at any problem we are faced with in life. It is with this idea we can see that science, carried out faithfully and in the public interest, possesses the answer to all our worldly problems and has the power to change the world.

And what does it mean to be a scientist? Does it mean someone like “Sheldon Cooper”, or a lab rat spending all day carrying out experiments? It can also be a doctor in a hospital, who runs tests on collected samples to see if their hypothesis—their diagnosis- is correct or not. It can also be one of our government leaders, among whom there are many accomplished scientists specialized in different areas of studies. Scientific training has helped them become more proficient as leaders of our society.

As for me and my team, our research fixes the eyes on one particular field: biomedical optics. The basic idea of this study is utilizing the power of light to solve problems crucial to our society that have risen in the realm of biology and medicine. Our research has three major branches, which are namely label-free microscopy, nanoscale Raman spectroscopy and imaging, and point of care technologies for resource-limited settings.

無(wú)標(biāo)記顯微技術(shù)

我們首先來(lái)看無(wú)標(biāo)記顯微技術(shù)。當(dāng)?shù)皖^看向自己的雙手時(shí)，我們可以分辨出它們的顏色和背景是不一樣的。這種顏色的區(qū)別使我們能夠?qū)⑻囟ㄊ挛锱c附近的東西區(qū)分開(kāi)來(lái)。但一個(gè)自然狀態(tài)下的細(xì)胞是無(wú)色的，導(dǎo)致研究人員要想對(duì)它直接進(jìn)行觀測(cè)會(huì)十分困難。所以，如果我們想鎖定某個(gè)分子并對(duì)其進(jìn)行觀察，就要首先賦予它一種顏色——一種熒光標(biāo)記——使它變得易于區(qū)分。舉個(gè)例子，科學(xué)家可以給艾滋病毒打上熒光標(biāo)記。感染了艾滋病毒的細(xì)胞會(huì)和健康的細(xì)胞進(jìn)行信息交換，為病毒創(chuàng)造一條通道，讓它能夠移動(dòng)到正常細(xì)胞內(nèi)并感染正常細(xì)胞。如果成功地給病毒貼上了一個(gè)熒光標(biāo)記，研究人員就可以順利觀測(cè)到艾滋病毒在細(xì)胞間的移動(dòng)現(xiàn)象，并進(jìn)一步對(duì)其進(jìn)行研究。

運(yùn)用新的技術(shù)，我們能夠清晰地看到細(xì)胞的內(nèi)部結(jié)構(gòu)

The Label-free Microscopy Technology

The first is the label-free microscopy technology. Looking down at our hands, we can tell they have a different color than the background, which enables us to tell them apart from things nearby. But a cell in its natural form is colorless, difficult for researchers to observe. So, should we wish to find a certain molecule and look at it, we first have to give it a color—a fluorescent label—thus making it discernible. For example, we can give a fluorescent label to an HIV virus. A cell infected with HIV will exchange information with a healthy cell, creating a tunnel for the virus to move to and infect the normal cell. If labeled with fluorescence, the cell-to-cell movement of the HIV virus will become observable for researchers.

As we can see from the example above, a fluorescent label is a powerful tool that allows us to see many things that have eluded our eyes before. Then why are scientists researching a “l(fā)abelfree” microscopy technology? First, the addition of a fluorescent label to a cell is challenging in itself—in fact, it might just kill the cell in the first place. Second, it is still not an easy task to observe the cell even with a fluorescent label. In order to capture better images, researchers will have to hit the labeled cell with a powerful laser beam, which will possibly overheat the cell or make it release toxic free radicals. Finally, even if researchers have succeeded in both labeling and keeping the cell alive, they still will face critical difficulty in observing it, since fluorescent labels can “break”, a process we call “photo-bleaching”, where the signal we receive gets weaker and weaker over time. Thus, the first image is very high quality, but the 10th or 20th image may be impossible to recognize. One of the solutions to this problem is to use a gentler laser, producing a poorer image of cells. Then we can take these poor-quality images and use a computer algorithm to help us enhance the quality, thus obtaining a relatively clearer image while protecting the cell. However, this method still has its limitations, and we nevertheless need to find other ways to observe the cell.

從這個(gè)例子中我們可以看出，熒光標(biāo)記是一個(gè)非常有用的工具。通過(guò)這項(xiàng)技術(shù)，我們能夠看到很多以前無(wú)法看到的東西。那么，為什么科學(xué)家們還要研究一種“無(wú)標(biāo)記”的顯微技術(shù)呢？原因在于，首先，給細(xì)胞打上熒光標(biāo)記本身就是一項(xiàng)挑戰(zhàn)。這一步驟很可能會(huì)直接殺死細(xì)胞。其次，即使有了熒光標(biāo)記，要觀察細(xì)胞仍然不是一件容易的事。為了捕捉到更好的圖像，研究人員必須用強(qiáng)大的激光束照射被標(biāo)記的細(xì)胞。這可能使得細(xì)胞過(guò)熱，或者釋放出有毒的自由基。最后，即使研究人員既成功地給細(xì)胞打上了標(biāo)記，又讓細(xì)胞存活了下來(lái)，他們?cè)谟^察細(xì)胞時(shí)仍然會(huì)面臨關(guān)鍵性的困難。這是因?yàn)闊晒鈽?biāo)記可能會(huì)“破損”，這個(gè)過(guò)程被稱為“光漂白”，即隨著時(shí)間的推移，我們接收到的信號(hào)會(huì)越來(lái)越弱。因此，第1張圖像的質(zhì)量通常會(huì)非常好，但第10張或第20張圖像可能會(huì)變得無(wú)法識(shí)別。解決這個(gè)問(wèn)題的方法之一是使用較溫和的激光。較溫和的激光生成的細(xì)胞圖像質(zhì)量較差，但我們可以利用計(jì)算機(jī)算法來(lái)幫助我們提高這些照片的成像質(zhì)量，從而在保護(hù)細(xì)胞的同時(shí)獲得相對(duì)更清晰的圖像。但是，這種方法仍然有其局限性，科學(xué)家們還是需要尋找其他的方法來(lái)觀察細(xì)胞。

To observe cells without fluorescent labels, scientists chose to utilize the outstanding work of Frits Zernike, the phase contrast microscope, (for which Zernike earned the Nobel Prize) and modify it to our demands. Beams of light that go through the cell move slower than those that move through the water surrounding the cell. This speed difference changes a property of light called its “phase”. Making use of this speed difference, the phase contrast microscope allows us to see colorless cells that are otherwise invisible. Yet the resolution of images coming from a phase contrast microscope is limited, and the information is “qualitative”, meaning that the brightness or dimness of certain parts of the cell cannot be exactly mapped to the cell’s real structure. Scientists need more to see better and as well deeper into a cell’s internal structure, and to make the measurement “quantitative”.

為了能夠在沒(méi)有熒光標(biāo)記的情況下觀察細(xì)胞，科學(xué)家們選用了弗里茨·澤爾尼克發(fā)明的相襯顯微鏡（澤爾尼克也因此獲得了諾貝爾獎(jiǎng)），并根據(jù)需要對(duì)其進(jìn)行了一些改進(jìn)。一束光在穿過(guò)細(xì)胞時(shí)的速度會(huì)比穿過(guò)細(xì)胞周圍的液體時(shí)要慢，這種速度差異會(huì)影響到光的一種被稱為“相位”的屬性。利用速度差，相襯顯微鏡可以讓觀測(cè)者看到原本難以看見(jiàn)的無(wú)色細(xì)胞。然而，相襯顯微鏡只能呈現(xiàn)有限分辨率的圖像，而且，這些圖像都是“定性”信息。也就是說(shuō)，圖像上細(xì)胞某些部位的明暗并不能準(zhǔn)確反映出細(xì)胞內(nèi)部的真實(shí)結(jié)構(gòu)?？茖W(xué)家們需要更適合的技術(shù)來(lái)更全面、深入地觀察細(xì)胞的內(nèi)部結(jié)構(gòu)，并使測(cè)量出的數(shù)據(jù)變得“定量”。

The devising of the ultra-oblique illumination high resolution phase contrast microscope technology affords us with new insights into cells that are alive and functioning. We can now clearly visualize most of the cell’s internal structure, including lipid droplets, nucleus, mitochondria, vesicles, and a very tiny web-like structure called the endoplasmic reticulum. We can also notice many things that haven’t yet to be found up to this moment. For example, with this new technology, we have found out that many of the mitochondria within certain cells are always spinning, as if the mitochondria are dancing. This movement costs the cell energy, but cells are very conservative and don’t like to waste any energy. Therefore, this mitochondrial dancing must have an important reason behind it. Now we need to use the scientific method, and devise a hypothesis we can test through experiment to discover the answer to this question. Since the phase image does not “photobleach”, and the imaging does not hurt the cell, scientists now also have all the time in the world to look at the endoplasmic reticulum, an important organelle, and study the biological function behind its incessant shaking motion.

超斜照明高分辨率相襯顯微鏡技術(shù)的出爐使得我們掌握了觀測(cè)活體正常細(xì)胞的全新角度。有了這項(xiàng)技術(shù)，科學(xué)家可以清晰地看到細(xì)胞內(nèi)部的大部分結(jié)構(gòu)，包括脂滴、細(xì)胞核、線粒體、液泡，以及一種非常微小的網(wǎng)狀結(jié)構(gòu)——內(nèi)質(zhì)網(wǎng)。我們還得以注意到從前沒(méi)有被發(fā)現(xiàn)過(guò)的東西。例如，我們發(fā)現(xiàn)在某些細(xì)胞內(nèi)，許多線粒體總是在不停旋轉(zhuǎn)，就像跳舞一樣。這種運(yùn)動(dòng)會(huì)消耗細(xì)胞的能量，但細(xì)胞通常都十分節(jié)約，不喜歡浪費(fèi)任何能量。因此，線粒體的這種“舞蹈”背后一定有著重要的原因。我們需要用科學(xué)的方法，提出一個(gè)假設(shè)，通過(guò)實(shí)驗(yàn)來(lái)檢驗(yàn)，由此發(fā)現(xiàn)這個(gè)問(wèn)題的答案。又如，內(nèi)質(zhì)網(wǎng)存在著一種不間斷的搖擺運(yùn)動(dòng)。由于新的顯微技術(shù)不存在“光漂白”效應(yīng)，也不會(huì)傷害細(xì)胞，所以科學(xué)家們現(xiàn)在有充分的時(shí)間去觀察內(nèi)質(zhì)網(wǎng)不停搖擺背后的生物功能。

拉曼光譜與成像

既然已經(jīng)能夠?qū)?xì)胞內(nèi)部進(jìn)行更清晰的觀察，科學(xué)家們便開(kāi)始設(shè)想，是否可以進(jìn)一步觀察出這些內(nèi)部結(jié)構(gòu)之間在化學(xué)成分上的差異？要滿足這個(gè)雄心壯志，科學(xué)家們需要一種名為拉曼光譜的技術(shù)。簡(jiǎn)單來(lái)講，科學(xué)家會(huì)將一種顏色的光照射向細(xì)胞，而由于光線與不同化學(xué)成分之間的相互作用，許多不同顏色的光束會(huì)從細(xì)胞里折射出來(lái)。在光譜儀的幫助下，這些不同的顏色可以被分離成被我們稱為“光譜”的信號(hào)，它可以告訴我們每種顏色各占多少。每個(gè)分子都有自己獨(dú)特的拉曼信號(hào)。而運(yùn)用拉曼光譜，我們可以分析出在細(xì)胞的每個(gè)部分存在著什么樣的化學(xué)分子。這項(xiàng)技術(shù)有著多種多樣的應(yīng)用。例如，通過(guò)觀察一個(gè)脂滴，科學(xué)家可以判斷出里面有什么，以及它是否由健康的脂肪構(gòu)成。通過(guò)進(jìn)一步分離并辨別細(xì)胞攝入的脂肪，我們甚至可以判斷出它是一個(gè)健康的細(xì)胞還是癌細(xì)胞。

Raman Spectroscopy and Imaging

With a clearer vision looking inside the cell, scientists also want to know, what are the chemical differences between these internal structures? The technique required for this ambition is called Raman spectroscopy. Basically, scientists shine one color of light onto a cell. Many different colors will come out from it due to the interaction of the light with different chemical components. With the help of a spectrometer, these colors can be separated into a signal we call a “spectrum”, which tells us how much of each color is present. The Raman spectrum can tell us what kind of chemicals are present within each point of the cell, because each molecule has its own unique Raman signal. Therefore, scientists, for example, can look at a lipid droplet and tell what’s inside and if it’s made of healthy fat or not. By separating the fat intake of a cell, we can even tell if it’s a healthy one or a cancer cell.

這項(xiàng)技術(shù)還可以從其他角度對(duì)癌癥進(jìn)行診斷。目前，“細(xì)胞外小體”的研究是生物學(xué)中的一個(gè)新興領(lǐng)域，其中最受關(guān)注的是“外泌體”。外泌體是一種納米級(jí)大小的信使，它的功能類似細(xì)胞之間溝通時(shí)所發(fā)送的“信件”。外泌體包含蛋白質(zhì)和核酸，可以向附近的細(xì)胞發(fā)出指令。但是，不僅正常細(xì)胞會(huì)釋放外泌體，癌細(xì)胞也會(huì)，而且數(shù)量往往比正常細(xì)胞多得多。事實(shí)上，癌細(xì)胞可以利用外泌體發(fā)送虛假信息，來(lái)欺騙本應(yīng)消滅它們的白細(xì)胞。在拉曼光譜儀下，我們能夠研究每一個(gè)外泌體的化學(xué)成分，并分析它們之間的微小差異。針對(duì)這一點(diǎn)，科學(xué)家們使用一種叫作“光鑷”的工具，挑選出單個(gè)的外泌體進(jìn)行深入研究。我們用這種方法發(fā)現(xiàn)，癌細(xì)胞和健康細(xì)胞的外泌體有著不同結(jié)構(gòu)的表面蛋白。這無(wú)疑將為癌癥的研究、診斷及可能的新治療手段提供參考。

This technology can take on cancer diagnosis from other perspectives. A new topic in biology is the study of “extracellular vesicles”, among which one of the most studied is called an “exosome”. The exosome is a nanoscale messenger. It functions like a letter sent between cells for communication purposes. It contains proteins and nucleic acids that can give instructions to nearby cells. Not only do normal cells release these exosomes, but cancer cells also release them, often in much higher numbers than normal cells. In fact, cancer cells can use exosomes to send false information to trick the white blood cells that are supposed to eliminate them. Using Raman spectroscopy, we can study the chemical composition of each individual exosome and see that every exosome is a little bit different from one another. Regarding this, scientists use a tool called optical tweezers to pick up each single exosome and examine them closely. We found that the surface protein of the exosome is different between a cancer cell and a healthy one, which can provide new information for cancer studies, cancer diagnosis, and possibly cancer treatments.

適于資源匱乏地區(qū)的醫(yī)療診斷技術(shù)

除了解決分子層面的生物學(xué)問(wèn)題，光學(xué)科學(xué)還可以為組織層面的醫(yī)學(xué)問(wèn)題作出貢獻(xiàn)。人們生病了會(huì)去“看醫(yī)生”，但其實(shí)是“醫(yī)生在看你”——醫(yī)生通過(guò)顯微鏡觀察你的組織或血液樣本。值得一提的是，近一個(gè)世紀(jì)以來(lái)，醫(yī)生使用的顯微技術(shù)幾乎沒(méi)有根本性的變革。也許，科學(xué)家們?cè)谙嚓P(guān)領(lǐng)域通力合作，如讓顯微鏡變得更小、更智能，也能推動(dòng)醫(yī)用顯微技術(shù)的進(jìn)步。

Care Technologies for Resource-limited Settings

Besides biological questions at the molecular level, optical science can also contribute to medical questions at a tissue level. When we are sick, it is natural for us to “see a doctor”. What really happens is “the doctor sees you”—the doctor looks at the tissue or blood sample of yours through a microscope. The microscopic technology used by doctors, in fact, hasn’t really changed in almost a century. Maybe through the coordinated efforts of scientists, we can improve medical microscopes, for instance, by making them smaller and smarter.

人們希望無(wú)論何時(shí)何地都能獲得高質(zhì)量的醫(yī)療服務(wù)。但在現(xiàn)實(shí)生活中，患者必須去到特定的地方——醫(yī)院——才能順利就診。醫(yī)院配備有所有可能需要的專業(yè)設(shè)備和儀器，它們將幫助醫(yī)生進(jìn)行測(cè)試，做出可靠、準(zhǔn)確的診斷。但這些設(shè)備往往體積龐大、價(jià)格昂貴，而且需要經(jīng)過(guò)大量的培訓(xùn)才能操作。如果你居住在一個(gè)發(fā)達(dá)國(guó)家的城市，這樣的資源對(duì)你來(lái)說(shuō)可能唾手可得。但那些生活在貧困（如非洲農(nóng)村）或偏遠(yuǎn)地區(qū)（如西藏地區(qū)）的人所面臨的情況就大不相同了，在那里資源稀缺且十分昂貴，患者往往需要幾天甚至幾周的時(shí)間才能就醫(yī)。為了讓醫(yī)療服務(wù)更方便、便捷，科學(xué)家們考慮將我們的日常工具改造成醫(yī)療設(shè)備。手機(jī)是否能夠承擔(dān)這樣的工作？它有攝像頭、麥克風(fēng)，內(nèi)置電腦和網(wǎng)絡(luò)模塊。如果再加上一個(gè)鏡頭，它基本上就能變成一臺(tái)顯微鏡，足以用來(lái)進(jìn)行疾病觀察、細(xì)胞計(jì)數(shù)，甚至成為一臺(tái)光譜儀。當(dāng)我們制造出這樣一個(gè)簡(jiǎn)單的手機(jī)顯微鏡時(shí)，我們發(fā)現(xiàn)它的確可以達(dá)到很好的顯微效果，觀察到細(xì)胞核和瘧疾寄生蟲(chóng)。然而，我們隨后發(fā)現(xiàn)，盡管手機(jī)顯微鏡具有成為便捷醫(yī)療工具的潛力，但它只適合那些具備專業(yè)操作技術(shù)的人。在手機(jī)顯微鏡的成像方面，由訓(xùn)練有素的實(shí)驗(yàn)室研究人員操作出的圖像和由醫(yī)院工作人員或其他沒(méi)有接受過(guò)使用培訓(xùn)的人操作出的圖像可能在質(zhì)量上差異很大。為了更適應(yīng)醫(yī)療衛(wèi)生從業(yè)的需要，我們的低成本顯微鏡必須更智能，必須對(duì)那些不十分熟悉光學(xué)科學(xué)的人更加友好。于是，我們研發(fā)出了一種新型“全自動(dòng)” 微鏡。它可以自動(dòng)聚焦和掃描微小的微觀樣品，體積小，便于攜帶，操作也不需要經(jīng)過(guò)額外培訓(xùn)，還能觀察從血液、糞便到組織樣品的多種類型的樣品。相比之下，雖然普通的自動(dòng)顯微鏡可以生成質(zhì)量稍好的圖像，但價(jià)格要比我們的顯微鏡貴很多倍。此外，新型顯微鏡非常便于組裝，材料在網(wǎng)上很容易就能買到，基本上就像一套樂(lè)高玩具一樣。

It is a universal dream to have access to high quality medical care whenever and wherever we want, which is in stark contrast to the reality where patients must go to certain places—hospitals—for that is where all the professional equipment and machines are. These machines help doctors run tests and make solid diagnoses. But they tend to be large, expensive, and require extensive training to operate. If you are an urban citizen in a developed country, such resources might be not so difficult to get. Things are very different for those live in poorer areas where such resources are scarce and exorbitantly priced, like rural Africa, or a remote district—like Tibet—where it takes days, even weeks, to reach a hospital.

To make medical services more convenient and accessible, scientists are thinking to turn everyday gadgets into medical devices. Can cellphone take up such a job? It has a camera, a microphone, a built-in computer and network modules. With a lens added on, a cellphone can be essentially modified into a microscope that can be used to look at diseases, count cells, and even become a spectrograph. When we developed a simple cellphone microscope, we found we could achieve excellent results, being able to see cell nuclei and malaria parasites. Yet for all the potential it has to become a convenient medical tool, we found out that it only suits those with specialized know-how, as images produced using a cellphone microscope can vary a great deal between those operated by trained lab researchers and those operated by hospital staff or others who have not been trained in the cellphone microscope’s use. In order to truly impact health care, our low-cost microscope must be made smarter and more friendly to those who are not so familiar with optical science. A new type of microscope was then made to satisfy this demand. It is a “fully-automated” microscope that can automatically focus and scan tiny microscopic samples, has a portable size, requires no additional training, and can look at many types of samples, from blood to feces to tissue samples. In comparison, a normal automated microscope can produce slightly better images, but is many times more expensive than our microscope. Ours is easy to put together, basically like a Lego set, and can be set up with materials that can be easily purchased online.

低成本、全自動(dòng)的顯微平臺(tái)

我們的自動(dòng)顯微鏡可以應(yīng)用于許多不同的醫(yī)療場(chǎng)景。它可以協(xié)助進(jìn)行動(dòng)物診療。眾所周知，山羊是雜食動(dòng)物，因此很容易遭到寄生蟲(chóng)的感染。在對(duì)山羊進(jìn)行寄生蟲(chóng)檢查時(shí)，獸醫(yī)通常會(huì)先從山羊的糞便中取樣，與水混合，然后再放在顯微鏡下分辨并歸類樣品中的寄生蟲(chóng)卵。如果采取純手工操作的方法，這套流程會(huì)非常累人。醫(yī)生一般需要花20—30分鐘的時(shí)間來(lái)仔細(xì)研究樣本。而我們的自動(dòng)顯微鏡可以自主對(duì)動(dòng)物的大便樣本進(jìn)行細(xì)節(jié)拍照，隨后利用深度學(xué)習(xí)技術(shù)，自動(dòng)從圖像中挑出蟲(chóng)卵，進(jìn)行計(jì)數(shù)，并分辨出這些蟲(chóng)卵是來(lái)自蛔蟲(chóng)、壯蟲(chóng)還是其他寄生蟲(chóng)。這樣一來(lái)，既節(jié)省了醫(yī)生的時(shí)間，又可以幫助動(dòng)物盡快得到正確的藥物治療，減少它們的痛苦。新型顯微鏡在人類體檢中也有用處。當(dāng)我們?nèi)タ床r(shí)，醫(yī)生通常會(huì)先抽取一小瓶血。通過(guò)統(tǒng)計(jì)血液中紅細(xì)胞、白細(xì)胞和血小板的數(shù)量，醫(yī)生能夠掌握我們的健康狀況。對(duì)于老年人，尤其是對(duì)罹患癌癥的老年人來(lái)說(shuō)，定期查血是很重要的一項(xiàng)檢查。治療癌癥的藥物不僅會(huì)殺死癌細(xì)胞，還會(huì)傷害到身體其他健康的部位，所以醫(yī)生要時(shí)刻監(jiān)測(cè)患者血液中的白細(xì)胞水平，避免其降低到臨界水平以下。目前，患者只能去醫(yī)院查血，而每個(gè)月可能只查一兩次。這就造成了醫(yī)生在信息掌握上的滯后。一種理想的情況是患者每天在家里就能自己驗(yàn)血。我們的新型、便捷、適合家庭使用的顯微鏡或許能夠?yàn)樗麄兲峁椭；颊呖梢詫⒀簶颖九c一種特殊液體混合，然后放在我們的顯微鏡下。顯微鏡會(huì)自動(dòng)掃描樣品，進(jìn)行分析，然后計(jì)數(shù)。不同種類的細(xì)胞——如紅細(xì)胞或白細(xì)胞——在輸出圖像中會(huì)顯示為不同的顏色或亮度。整個(gè)系統(tǒng)完全自動(dòng)，所以即使是由業(yè)余的爸爸媽媽們來(lái)操作，得出的檢測(cè)結(jié)果也可以和專業(yè)的研究人員一樣準(zhǔn)確、可靠。

Our automated microscope can find application in many different medical scenarios. As one example, we have shown how it can help treat animals. Goats are known to be messy eaters, and are consequently very easily infected by parasites like parasitic worms. The usual procedure for a vet to perform a parasite check on a goat is first taking a sample from its feces, mixing it with water, then putting it under a microscope to tell apart and classify the parasite eggs in the sample. This can be exhausting if done manually. It usually takes 20—30 minutes of the doctor’s careful study. Our automated microscope can take a detailed pictures of a large sample of the animal’s feces and, subsequently, using deep learning technology, pick out eggs from the image automatically, count them, and tell us if they are from ascarids, strongyles or other parasites. This can save the doctor’s time, and help the animal to get the correct drug as soon as possible, reducing its suffering.

This can also be applied to the medical examination for human beings. When seeing a doctor, it is a common practice to have a vial of blood taken. By counting the number of red blood cells, white blood cells and platelets, our blood serves as a window of our health status in the eyes of a doctor. Regular blood checkups are important for the elderly, especially those who have cancer. Drugs used in cancer treatment will not only kill the cancer cells but also hurt the healthy body parts, so doctors will want to monitor the white blood cell level in the patient’s blood to avoid it reducing beyond a critical level. Using current technology, patients have their blood tested only when going to a hospital, which probably only happens once or twice a month. This creates a time-lag of information on the doctor’s side. The ideal for us is to enable the patient to have his or her blood tested right at their own homes on a daily basis. Our new, convenient, household friendly microscope is qualified to help. Blood samples from patients will be mixed with a special liquid that prepares the sample and put under our microscope. Samples will be automatically scanned, analyzed and counted. Different kinds of cells, like red cells or different types of white blood cells in the output image will have different colors or brightness. Because the system is totally automatic, in our experiments the test results obtained by amateur moms and dads can be just as accurate and reliable as those of professional researchers.

即使是要給動(dòng)物抽血，我們的顯微鏡也能幫上忙。動(dòng)物并不了解健康檢查的重要性，所以，為了抽血這一過(guò)程不刺激到它們或讓它們不安，醫(yī)務(wù)人員會(huì)盡可能輕柔地從它們身上抽取盡可能少量的血。我們的系統(tǒng)只需要幾微升（不到一滴）的血液就足以得到準(zhǔn)確的檢測(cè)結(jié)果，因此能夠非常好地適應(yīng)這項(xiàng)工作的特殊條件。

And even when it comes to draw blood from animals, our microscope can get the job done. Animals don’t understand the importance of health check-ups. To not irritate or upset them, medical practitioners would wish to take as little blood as possible from them, and in the most gentle manner. Our system requires only a few microliters (less than one drop) of blood, and it’s sufficient to get an accurate test result.

最后，我們的技術(shù)還可以在另一個(gè)重要領(lǐng)域——貧血診斷——中發(fā)揮作用。貧血是全球公共衛(wèi)生面臨的一大嚴(yán)重威脅，影響著全球約1/3的人口，尤其是那些醫(yī)療資源稀缺地區(qū)的人。中國(guó)有10%—20%的兒童患有缺鐵性貧血，通常與營(yíng)養(yǎng)不良有關(guān)；有4300萬(wàn)兒童患有地中海貧血，這是一種遺傳性貧血，常見(jiàn)于泰國(guó)、越南及中國(guó)的廣東和廣西。這兩種不同的疾病對(duì)治療方法有著不同的要求。對(duì)于缺鐵性貧血，治療方法可以非常簡(jiǎn)單——提高鐵質(zhì)攝入量；然而，對(duì)于地中海貧血的患者來(lái)說(shuō)則相反，鐵的攝入對(duì)他們非常危險(xiǎn)。正因如此，我們希望能夠?qū)ι鐣?huì)中的每個(gè)公民進(jìn)行貧血檢測(cè)。但讓全國(guó)人民都去醫(yī)院看病檢測(cè)是一件不可能的事，所以我們需要研發(fā)一種儀器，可以在醫(yī)院外使用，價(jià)格便宜，每個(gè)城市都可以有幾個(gè)這樣的儀器。在貧血篩查過(guò)程中，第一項(xiàng)任務(wù)是找到那些貧血的人;第二項(xiàng)任務(wù)是診斷出患者所患的是哪種貧血。人體內(nèi)紅細(xì)胞的形狀和大小不盡相同，而健康人、缺鐵性貧血患者和地中海貧血患者之間的紅細(xì)胞也不一樣。但是，由于缺鐵性貧血患者和地中海貧血患者的紅細(xì)胞大小及形狀的差異非常微小，所以，通常需要大型昂貴的設(shè)備才能成功區(qū)分。這些設(shè)備在醫(yī)院以外的地方很難操作，所以我們采用了一種低成本的光學(xué)散射系統(tǒng)來(lái)測(cè)量紅細(xì)胞的大小、形狀或血紅蛋白濃度等參數(shù)。通過(guò)我們這套系統(tǒng)產(chǎn)生的數(shù)據(jù)，醫(yī)生幾乎可以100%準(zhǔn)確地區(qū)分貧血患者和健康人。在缺鐵性貧血患者和地中海貧血患者的區(qū)分上，這套系統(tǒng)能達(dá)到超過(guò)90%的準(zhǔn)確率。我們希望在未來(lái)，這樣的技術(shù)可以順利應(yīng)用于大范圍、全人口的貧血篩查。

Last but not least, there is one more application where our technology can pitch in—the diagnosis of anemia. Anemia is a serious threat to public health globally as it’s affecting around one third of the world’s population, especially plaguing those who have the least access to competent medical resources. 10%～20% percent of children in China have iron deficiency anemia, which is related to malnutrition; 43 million in China have thalassemia, a genetic type of anemia, which is commonly found in Thailand, Vietnam, Guangdong and Guangxi in China. These two different diseases should be countered with different treatments. For iron deficiency anemia, the solution can be as simple as boosting up one’s iron intake. Yet on the contrary, iron intake is dangerous for patients with thalassemia. Because of this, we would like to test every citizen for anemia, but it’s not possible to have the whole country go to the doctor to get tested. We need to make an instrument which can be taken outside of the hospital, and is inexpensive enough that every town can have several such instruments. In this screening process the first job is to find those with anemia and the second job is to tell which kind of anemia it is. Blood cells are not the same in shapes and sizes, and they are different among a healthy person, an iron deficiency anemia patient and a thalassemia patient. However, because the size and shape differences are very tiny in iron deficiency and thalassemia, to differentiate blood cells according to their sizes normally requires large and expensive devices that are not easy to operate outside of a hospital. So we have come up with a low cost optical scattering system that can be used to measure parameters of red blood cells like size, shape, or hemoglobin concentration. With data produced from our system, doctors can tell an anemic patient from healthy people with nearly 100% accuracy, and separate iron deficiency anemia patients and thalassemia patients with an accuracy over 90%. We hope in the future such a technology could be used for widespread, whole population screening of anemia.

光的力量可以幫助我們解決許多生物和醫(yī)學(xué)上的問(wèn)題，助力我們改善現(xiàn)在所處的社會(huì)。光學(xué)科學(xué)的發(fā)展是許多杰出科學(xué)家努力的結(jié)果。每一位科學(xué)家都是“站在巨人的肩膀上”貢獻(xiàn)自己的微薄之力。在他們的共同貢獻(xiàn)下，世界可以變得更加美好。

The power of light can help solve many biological and medical questions, tackle challenges, and change the society we are now living in. The development of optical science is the results of effort from many outstanding scientists. Each scientist “stands on the shoulders of giants”, and tries to add their own small contribution to the greater good. Thanks to their combined contributions, the world can be a better place for all of us.