The revolutionary technology that changed the world in 2014

Release date: 2014-12-23

Gene editing is faster, more accurate and simpler

In 1973, Stanley N. Cohen and Herbert W. Boyer found ways to change the genome of living organisms and successfully inserted the DNA of the frog into the bacteria. In the late 1970s, Genetech of Boyer genetically engineered E. coli with a human gene (this gene is synthetic) and finally produced insulin for diabetes. Soon, scientists at the Salk Institute for Biological Studies in La Jolla, California, developed the first transgenic mice.

In the 1970s, scientists found ways to change the genome of living organisms, but these methods were inaccurate and difficult to use in mass production. Therefore, many genetic modification experiments are still difficult and expensive.

Now, a new technology called CRISPR may revolutionize genome editing. This technology is derived from the immune defense system of bacteria and is faster, cheaper and simpler than traditional methods. Commercialized CRISPR technology companies have attracted a lot of money.

Researchers have begun to explore how to apply CRISPR technology to the treatment of various diseases such as AIDS and schizophrenia. However, because CRISPR can change the genomes of plants, insects and humans very easily, ethicists worry that this will have some negative consequences.

These great achievements in the field of genetic engineering have changed the course of modern medicine. However, early genetic modification methods have two major limitations: they are not very accurate and are difficult to mass produce. At that time, the behavior of DNA insertion into the genome was random, and scientists could only pray for good luck, and hopefully they would get a useful mutation. In 1990, researchers made leaps and bounds. They designed a protein that cleaves DNA at a specific site, breaking through the first limitation. However, every time they want to modify a DNA sequence, they have to design a new protein, which is very time consuming and very difficult.

Time has finally arrived in 2012. Researchers led by Emmanuelle Charpentier of Ume? University and Jennifer Doudna of the University of California at Berkeley report that they found in cells A genetic mechanism that allows scientists to edit genomes at an unprecedented rate, and the process is simple. Shortly thereafter, a team at Harvard University and the Massachusetts Institute of Technology used this technique to modify multiple sites in the cell genome at once.

This advanced technology has accelerated the development of the genetic engineering industry and has a profound role in promoting genetics and medicine. Scientists can now customize genetically modified experimental animals on demand, in a matter of weeks, eliminating the amount of work and time from the previous year. Researchers are currently using the technology to explore treatments for diseases such as AIDS, Alzheimer's disease, and schizophrenia. The technology makes the genetic modification process of organisms quite simple and cheap, and researchers and ethicists are even beginning to worry that this will have a negative effect.

This technique, called CRISPR, is an abbreviation for "clustered, regular interspaced, short palindromic repeats" (ie, clustered, regularly spaced short palindromic repeats). Using this sequence, bacteria can "memorize" the virus that has invaded it. Scientists have been studying this strange gene sequence since the discovery of CRISPR by Japanese scientists in the late 1980s. However, until Dudna and Carpentier accidentally noticed a protein called Cas9, CRISPR showed its great potential as a genome editing tool.

In 2011, Dudna and Carpentier met at a scientific conference in San Juan, Puerto Rico. They have a lot in common: their team is studying the mechanism of bacterial defense against virus intrusion; they have all confirmed that bacteria can remember the DNA that had previously invaded their own virus to identify the virus, when the virus invades again, They will immediately recognize the "enemy."

Shortly after that meeting, Carpentier and Dudna decided to cooperate. At the time, Carpentier had just discovered in the lab of the University of Umeå that Streptococcus seems to use Cas9 protein to "crush" the virus that breaks through its cell wall. Thus, Dudna began to explore the mechanism of action of Cas9 protein in Berkeley's laboratory.

There are a series of clever things behind many scientific discoveries, and the story of CRISPR is no exception. Krzysztof Chylinski of the Carpentier Laboratory and Martin Jinek of the Dudner Lab grew up in the neighboring towns and spoke the same Polish dialect. Du Dena said: "They started chatting through Skype. The two hit it off and then began sharing data and discussing ideas for experimentation. This project officially started."

Scientists in both laboratories are aware that they may be able to use the Cas9 protein for genome editing. Genome editing is a method in genetic engineering. The enzyme is a "molecular scissors" in this process that can cut DNA. This enzyme, called nuclease, cleaves double-stranded DNA at specific sites. After DNA breaks, the cell repairs the site of the break. Sometimes, some of the cells in the cell are introduced into the gene fragment, which will be inserted during the repair process. When Dudna and Carpentier started working together, if scientists wanted to change or shut down a gene, the most advanced method was to customize an enzyme that could find and cleave specific DNA sites. In other words, every time a gene is modified, scientists have to design a new protein that specifically targets the DNA sequence that they want to modify.

But Dudna and Carpentier realized that the Cas9 protein, the enzyme used by this streptococcus for immune defense, uses RNA to guide itself to the target DNA. In order to detect the site of action, the Cas9-RNA complex will "bounce" on the DNA until it finds the correct site. This process seems random, but it is not. Each bounce of the Cas9 protein is searching for the same short "signal" sequence. Cas9 will attach to the DNA and detect if the adjacent sequence matches the RNA acting as a guide. This RNA is called guide RNA (gRNA), and the Cas9 protein cleaves DNA only when it matches the DNA. If the natural RNA guide system can be used, researchers don't have to build a new enzyme every time they cut DNA sites. Genomic editing may therefore become simpler, cheaper, and more effective.

The transatlantic team worked together on the Cas9 protein for several months and made a breakthrough. Du Dena can still remember that moment clearly. Their lab is located on a tree-lined hillside on the edge of the Berkeley campus, opposite the Greek Theatre, where Inek, who is still doing postdoctoral research, has been experimenting with Cas9 protein. One day, he came to Dudna's office to discuss the results of the experiment. Faced with a problem that Ianike and Helinsky have been discussing, they are immersed in meditation: in nature - that is, in streptococci, Cas9 protein relies not on one but two RNAs to guide itself. Look for the right spot on the DNA.

What if you combine two gRNAs into one RNA strand while preserving their wizard function? If you only need to modify an RNA sequence, the speed of the researcher will be greatly improved. There is a subtle complementarity between the gRNA sequence and the target DNA sequence, and using this relationship to construct a gRNA is easier than customizing a nuclease.

"Looking at the data, we suddenly opened up - this kind of thing happens often," Dudna said. "We realized that these RNA molecules can actually be designed as a gRNA. A system consisting of a protein and a gRNA. It is enough to be a powerful genetic modification tool. I shuddered and thought, 'God, I have to go to the lab quickly, if this can be successful...'"

They really succeeded. The result exceeded Dudner's vision (although she had high expectations). On August 17, 2012, when Dudna and Carpentier made their research on CRISPR-Cas9 public, scientists in the field immediately realized the transformative power of this technology, they all want to know about CRISPR- What a Cas9 can do, a global competition kicked off.

How does CRISPR work? CRISPR is the "weapon" of bacteria that "crushes" the DNA of viruses that invade bacteria. Scientists can use this tool to change the DNA sequence they want to modify. Unlike previous genome editing methods, the CRISPR system uses a common enzyme, Cas9, to perform clipping. What researchers need to do is to make a gRNA to guide Cas9, and synthesizing an RNA is much easier than synthesizing an enzyme.

Before 2013, researchers have been trying to apply CRISPR-Cas9 to plants and animal cells – they are much more complicated than bacteria. In their view, this is as exciting as the resurrection of Neanderthals and mammoths. At Harvard University, a team led by geneticist George Church uses CRISPR technology to transform human genes, providing multiple possibilities for the treatment of disease.

CRISPR-Cas9 quickly became a hot spot for investment. More than a year ago, Du Dena teamed up with Church, Zhang Feng of the Massachusetts Institute of Technology and other researchers to form Editas Medicine, which received $43 million in venture capital to develop a New, CRISPR-based drugs (the company has yet to disclose what kind of disease they are targeting first). In April 2014, CRISPR Therapeutics, a $25 million investment company, was established in Basel, Switzerland and London, UK, and their goal is to develop CRISPR-based disease therapies. Both Adidas Pharmaceuticals and CRISPR Medical will take years to develop the appropriate therapies, however, laboratory suppliers are already selling CRISPR materials that can be used immediately for animal injections to customers around the world, and Beginning to customize CRISPR-modified mice, rats and rabbits for customers.

This year, I visited SAGE Labs in St. Louis on a wet summer day, one of the first companies approved to use Dudna's CRISPR technology to transform rodents. There, I can see for myself how CRISPR works. SAGE Lab supplies experimental materials to approximately 20 top pharmaceutical companies, as well as numerous universities, research institutes and foundations. The Horizon Discovery Group, a biotechnology company based in Cambridge, UK, has previously independently involved in the development of CRISPR products; in September 2014, they acquired SAGE Labs for $48 million. The SAGE lab is located in an industrial park built in a low-rise office building at the end of a road. The scientists here received an online order from the lab: a laboratory in Sacramento, Calif., for the study of Parkinson's disease, ordering 20 mice that knocked out the Pink1 gene. The newly renovated side building cost $2 million and is custom-built genetically modified rats and other CRISPR-modified rodents. The animals live in ultra-clean, constant-temperature cages, and the cages are placed neatly together, from the floor to the ceiling. The staff fills in the order, selects the corresponding 20 rats, gently packs them in a box, and then airs them to California – the whole process is as simple as that. If someone wants to study schizophrenia or pain control, they can also order experimental animals like this.

However, if there are no animals in the warehouse that the customer wants to customize, the process is different. For example, one client wanted to study the relationship between Parkinson's disease and a newly discovered suspicious gene (or a specific mutation in a gene). When he went to the SAGE lab to order rodents, there were several options. Scientists at SAGE Labs can use CRISPR technology to "turn off" the target gene to create a mutation; they can also turn off the target gene and then insert a human gene into it. From Parkinson's disease to cystic fibrosis to AIDS, many diseases are associated with genetic mutations. In the past, scientists took a year to develop these experimental animals with complex genetic mutations. But CRISPR is different from previous genome editing techniques. Using this technology, researchers can quickly change multiple genes simultaneously within a cell. The time to cultivate genetically engineered animals has therefore been shortened to a few weeks.

SAGE employees first use chemical kits to synthesize custom DNA and RNA that matches this DNA. They mixed RNA and Cas9 proteins in a Petri dish, and a CRISPR tool with genome editing capabilities was born. They then spend about a week testing the function of the tool in animal cells with an instrument that looks like a scanner. This instrument is capable of emitting current and injecting CRISPR tools into cells. The CRISPR tool that enters the cell will start working immediately, cutting the DNA and performing small amounts of gene insertion and deletion. CRISPR is not 100% effective: in some cells, they cut DNA, make mutations, and in others do not work at all. To see how the performance of CRISPR is going, scientists collect DNA from cells, pool them, and replicate multiple copies of DNA fragments near the target site. They process and analyze the DNA and then view the results of the analysis displayed on the computer screen. If CRISPR successfully cuts the target site and creates a mutation, a blurred band appears on the screen, and the more DNA cut by CRISPR, the brighter the band. Next, the “battlefield” was transferred to the animal laboratory in the wing. Scientists are here to make genetically engineered embryos, as well as mutant rodents. The biologist Andrew Brown wore surgical gloves, blue robes, overshoes and fluffy hats, bent over the dissecting microscope. He sucked up a rat embryo with the tip of a glass pipette, then walked to the other end of the room and transferred the embryo to another microscope with a robotic arm. He placed the embryo in a drop of liquid on the slide and fixed it to the table. Now, CRISPR is about to play its magic: he controls the joystick with his right hand, and a robotic arm plunges an empty glass needle into the embryo.

From the eyepiece of the microscope, the two pronucleus from the parents in the embryo are like a crater on the surface of the moon. Brown gently pushes the cell until one of the pronuclei moves to the side of the tip. He clicks on the computer mouse and a drop of liquid containing CRISPR is ejected from the needle and passes through the cell membrane into the cell. The pronucleus immediately swells like a fast-bloomed flower. Brown had a good luck, and a mutant cell was born. There are three technicians in the SAGE lab who repeat the work four times a day, four days a week.

Brown will complete the injection of the rat embryo into the pipette, move it into the culture dish, and store it in an incubator that is heated to the animal's body temperature. Finally, he needs to inject 30 to 40 modified embryos into the surrogate mother. After 20 days, surrogate rats will be pregnant with 5 to 20 "children". When these "children" grow to 10 days old, scientists at SAGE Lab will take tissue samples to test which "children" have been modified. gene.

“This is the most exciting time,” Brown said. Of the 20 embryos, only 1 can be successfully transformed, and the successful animal is what we call the founder animal. At this point, everyone will celebrate. In our opinion, the scientists at SAGE Labs who make RNA and inject embryos seem simple, and many laboratories use the same steps to grow genetically engineered animals. As SAGE's CEO, David Smoller, says, this is a genome editing technique that can be “quantitized”.

CRISPR has bravely embarked on a commercial journey, and researchers and businessmen are envisioning new commercial uses for this technology, some of which are even arrogant. Using this technique, doctors may be able to engineer abnormal chromosomes associated with Down's syndrome in early pregnancy; breeders can reintroduce herbicide-sensitive genes into the genome of resistant weeds; we can also resurrect Extinct species. This of course will make some people feel scared. For example, there have been some warning headlines recently, describing this technique as "a good way to play God," or "bottle in the bottle." These articles worry that when we are eager to get rid of malaria mosquitoes, want to cure Huntington's disease too much, or expect to "design" a better baby, we may also be creating a "Jurassic Park" full of harmful new genes.

Take the “Anti-mosquito Project” proposed by Harvard University researchers as an example. Todd Kuiken, a biosafety analyst at the Woodrow Wilson International Center for Scholars, believes that fighting malaria parasites is one thing, but destroying the parasite's carrier , but it is another task that is completely different. If our goal is to eradicate malaria, a disease that infects 200 million people every year and kills 600,000 people, we have to be careful whether we will create 10 new troubles. "We have to think clearly, 'Do we really want to do this?' If the answer is 'yes', what systems do we have? What kind of safeguards are there?"

Scientists are moving fast, and they want to anticipate the most likely hazards of CRISPR technology and develop countermeasures. On July 17, 2014, when the Harvard team published a paper discussing how to use CRISPR to eradicate malaria mosquitoes, they also called on the public to discuss the issue. They also pointed out the technical and regulatory aspects of genetic modification. Dilemma. The team's bioethicist Jeanneine Lunshof said: "CRISPR is developing so fast that many people have not heard of it, but we are actually using it. This is a new Phenomenon. Now, under the framework of Berkeley's Innovative Genomics Initiative, Dudna is forming a team to discuss the ethical issues of applying CRISPR. If concerns about ethical issues put out people's enthusiasm for CRISPR, the consequences will be unthinkable. For example, in June 2014, researchers at the Massachusetts Institute of Technology reported that they injected CRISPR directly into the animal from the tail to cure adult mice with tyrosinemia, a rare liver disease. This disease is caused by a mutant enzyme. The researchers injected three gRNA sequences and Cas9 proteins into the mice, as well as the correct DNA sequence of the mutant gene. One out of every 250 liver cells in mice is inserted with the correct gene. The next month, the "corrected" liver cells thrived and eventually replaced 1/3 of the diseased cells - enough to get the mice out of the disease. In August 2014, researchers led by virologist Kamel Khalili of Temple University reported that they have used CRISPR to cut HIV in several human cell lines. cut.

Since the 1980s, Khalili has been fighting the front line against HIV/AIDS. For him, CRISPR is a revolution that is uncompromising. Although AIDS treatment has made great progress, today's drugs can only control the virus and still cannot eradicate the disease. However, with CRISPR, the Harley team has completely eliminated the complete DNA copy of HIV from the cells and transformed the infected cells into virus-free cells. And, in addition to "cleaning" cells that have been infected with the virus, CRISPR can also integrate a viral sequence into uninfected cells to immunize it - as Dudna and her team observed in the original bacteria. You can call this a "gene vaccine." "This is the ultimate treatment," Khalili said. "If you asked me two years ago, 'Can you cut HIV in human cells precisely?' I might say it is very difficult. But now, we did it. ."

Programmable cell

By gently squeezing the cells, some macromolecules or nanomaterials can enter the cell, which in turn changes the function of the cell.

If humans can let cells in the body work according to our requirements, such as letting them synthesize insulin in time, or attacking tumors, many health problems will be solved. However, achieving this desire is not easy. The method currently used is to use the virus to penetrate the cell membrane and intervene in the cells, but this will cause permanent damage to the cells.

In 2009, researchers at the Massachusetts Institute of Technology inadvertently solved this technical problem. They were trying to inject some macromolecules and nanomaterials into the cells with a microscopic water gun. These substances can change the working mechanism of the cells while ensuring cell survival. Chemical engineer Armon Sharei found that the impact of the water gun caused a brief distortion in the shape of some of the cells.

Surprisingly, when the shape of the cell is in a distorted state, the injected substance successfully enters the cell. Sharay said: "This makes us realize that if the cells are deformed in a short enough time, they can temporarily overcome the obstruction of the cell membrane." In any case, the microscopic water gun is only a more extensive method, the next step. Is to find a more gentle way to squeeze cells.

To this end, Klavs F. Jensen, one of the founders of microfluidics, and Robert S. Langer, another pioneer in the field of biology, Under the leadership, Sharay developed a microchip based on silicon and glass. The surface of the chip is pre-etched with a channel for cell flow, and as the cell flows, the channel gradually narrows until the cell cannot continue to move forward. At this time, the stuck cells are deformed by being squeezed, and small holes appear on the cell membrane. The diameter of these pores is sufficient for many mediators that can change the function of cells, such as proteins, nucleic acids, carbon nanotubes, and the like.

This technology can even successfully introduce media into fragile stem cells and immune cells that cannot withstand the smashing of previous extrusion methods. “There are so many kinds of cells that this technology can use, so we can’t expect it,” Sharay said.

Since the advent of this technology, Sharay's research team has developed 16 chips for different cells. Of course, there will be more chips coming out. Moreover, on the basis of the existing extrusion of 500,000 cells per second, the processing efficiency of related equipment will be further improved. The team has set up a company called "SQZ Biotechnology" to bring this technology to market. Researchers in France, Germany, the Netherlands and the UK are expected to use the technology very quickly.

Transparent animal

By injecting special compounds, animals can be made transparent, and this technology will become a booster in the development of biomedical fields.

Five years ago, Viviana Gradinaru also slowly processed two-dimensional images of mouse brain slices and synthesized them into three-dimensional models in a neurobiology laboratory. One day, she visited the “Body World” specimen exhibition. What fascinates her most in the entire exhibition is the plasticized, complete human circulation system. This exhibit made her deeply feel that similar treatments can be applied to her research field, greatly improving the efficiency of the experiment.

The concept of "tissue stripping" has been proposed for more than 100 years, but the methods at the time, such as the use of solvent soaking, are very inefficient and often destroy the fluorescent proteins required for labeling cells. In order to find a better solution, Graddinaru, a graduate student at the time, conducted research with colleagues from the late neuroimmunologist Paul Patterson lab. The purpose of these studies is to replace the fat molecules in the tissue - it is fat that makes the tissue opaque. However, they must find a substance that can replace fat to support the structure of the tissue.

In the end, they found the right method: first euthanasia of rodents, and injection of formaldehyde into the body, using the heart to pump formaldehyde to the body of the animal; afterwards, peeling off the skin of the animal, injecting a kind of acrylamide from the blood vessels A white, odorless compound of acrylamide monomers. The acrylamide monomer can establish a supporting hydrogel network in the animal to replace the fat in the animal tissue and make it colorless. Within two weeks, this substance can make a mouse become Transparent throughout.

Shortly after the birth of this method, they began to try to draw a complete neural network of transparent mice. Transparent organs have made many of their dreams come true, such as distinguishing peripheral nerves - such tiny bundles of nerves that people knew little before. For example, a fluorescently labeled virus is injected into the tail of a transparent mouse to observe how the virus enters the brain of the mouse through the blood-brain barrier. "Mastering this technology is like having a 'perspective eye' that has insight into everything in the world," Glydinaru said. On the one hand, transparent organs can reduce the probability of human error in the experiment, on the other hand, it can improve the experimental efficiency, enrich the experimental data, and reduce the number of experimental animals. Glydinaru is willing to provide her hydrogel making method to any laboratory in need. Next, she will extend this technology to cancer and stem cell research.

Simple and fast nano microscope

An electron microscope that can capture nanoparticles can quickly detect molecular information in drugs and explosives.

Electron microscopy with nanometer-scale resolution has been widely used, but its price is as high as millions of dollars, and preparing samples is also very troublesome. This is acceptable for professional research labs, but if you want to quickly scan product samples to see the built-in microscale watermarks?

A new holographic microscope developed by New York University physicist David Grier and colleagues can solve this problem. Based on a commercial Zeiss microscope, they replaced their incandescent light source with a laser source. The laser light is irradiated onto the sample to be observed, and then scattering occurs to form a three-dimensional image (ie, a hologram) in which the laser beam and the scattered light interfere with each other, and is recorded by the camera.

Scientists have been able to generate holographic images of microscale objects for decades, but it is always difficult to extract useful information from them. This is the value of Greer's invention. His research team has written a software that can quickly solve unknown parameters in equations that describe the scattering of light on a sphere. These parameters contain all the information about the scattering object. Because of the nanoscale resolution of this microscope, researchers were able to track particles suspended in the colloid (such as floating nanobeads in paint samples). At the same time, its cost is only one tenth of that of an electron microscope.

Greer hopes that this instrument will provide a fast and economical way to observe individual particles inside the product. Imagine that every drop of liquid in a paint bucket or shampoo bottle contains particles that are labeled with product production information – just like a fingerprint. Greer added that the microscope is also easy to "read" the molecular information "drugs" in drugs, explosives and other items.

Liquid power generation

Saliva may become a new source of energy for medical devices.

Muhammad Mustafa Hussain, a professor at the King Abdullah University of Science and Technology in Saudi Arabia, dedicated his life to the development of ultra-miniature devices. . He summed up his research in one sentence: “Small things have brought us closer to the future.” So when he started researching efficient, renewable power generation equipment in 2010, he provided sufficient water purification or medical diagnosis in remote areas. When energy is used, the first factor he considers is small. However, the use of saliva to drive fuel cells was completely unimagined at the beginning of the study.

The idea of ​​"spit" came from a colleague at the time at Hussein Labs, who was studying for a Ph.D., Justine E. Mink (now a researcher at The Dow Chemical Company). At that time, Mink was trying to develop a micro-device that could be implanted in the human body and placed near the pancreas to monitor blood sugar levels in diabetics. Microbial fuel cells – this is reflected in the way that bacteria supply organic matter (the saliva is also rich in organic matter) and use bacteria to produce electricity. It happened that she and Hussein could use this method, so the two found a highly conductive graphene electrode with saliva bacteria attached. Within a week, the bacteria produced 1 microwatt (millions). The amount of electricity is divided into one watt).

Although 1 microwatt seems insignificant, it is enough to drive tiny devices such as chips, diagnostic tools, or Mink's diabetes monitors. Hussein is now working with a 3D printed artificial organ company to embed his fuel cell into an artificial kidney and charge the battery through various body fluids. He said that this is only the first step of his ambitious goal. In the future, he intends to help poor countries to use the organic matter in industrial waste to generate electricity and use it for seawater desalination.

"Atomic building blocks" to build novel materials

The discovery of new materials will always promote the progress of human civilization. This is the driving force for human society from the Stone Age to the Bronze Age, to the Iron Age, and finally to the Silicon Age.

Lego bricks are a magical plastic toy that constantly inspires new ideas. The plastic components of LEGO bricks are small and can be combined in different ways to become magical cars, cleverly designed castles and many other structures. Today, a new generation of materials scientists are inspired by LEGO bricks to apply this combination to the nanoworld.

The building block components here are some layered materials. The thinnest of these materials can reach only one layer of atoms, which can be stacked one after another in a precise order according to the designed structure. This unprecedented combination of precision creates new materials with unprecedented electrical and optical properties. Scientists further envisioned the use of these materials to create electrically conductive materials with virtually no resistance, more powerful computing, faster computers, and wearable electronics that are bendable, foldable, and very light.

These groundbreaking studies were created by the appearance of graphene. Graphene is a new graphite material with a sheet structure. It has only one atom in thickness and its atomic structure is a repeating hexagon. It looks like a barbed wire fence. In 2004, my colleague from the University of Manchester in the United Kingdom isolated a single-layer graphite sheet, graphene, from a piece of graphite by using a tape to peel off a piece of crystal of one atom thick from the top of the bulk graphite. Over the past 10 years, researchers have discovered dozens of massive crystals that can be stripped by this method, and such crystals are growing. Mica is one of the crystals, and there are some unique materials, such as hexagonal boron nitride and molybdenum disulfide.

These crystal layers are considered to be two-dimensional materials, because for any material, the minimum thickness is a single atomic thickness (slightly thicker crystals, such as three or so atomic thicknesses, can also be considered two-dimensional). Depending on the needs of the manufacturer, the other dimensions of the crystal layer - width and length - can be very large. Because of their many unique properties, two-dimensional crystals have become a hot topic in materials science and solid physics in the past few years.

We can stack these crystal layers very stably together. They are not connected by chemical bonds in the usual way, such as covalent bonds that share electrons. When they are very close to each other, the atoms will attract each other through the well-known weak van der Waals forces. This force is usually not large enough to aggregate multiple atoms or molecules together, but because the atoms of these two-dimensional crystal layers are very dense and the distance between them is very close, these forces are added together and become very powerful. .

In order to understand the tempting possibilities of this material, we can think about room temperature superconductivity. It has been the dream of generations of scientists to achieve current transmission without energy loss without the need to place the device in an ultra-low temperature environment. If you find a material that can achieve this goal, it will have a very profound impact on human civilization. The consensus of the researchers is that in principle this goal is achievable, but no one knows how to achieve it. To this day, the maximum critical temperature of the superconducting material (the temperature at which the superconducting material changes from a normal state to a superconducting state) is also below -100 °C. Progress in this area has been very limited over the past 20 years.

We have recently discovered that many of the oxides (compounds composed of at least one oxygen atom and many other elements) superconductors can be decomposed into a sheet structure having a thickness of one atom using the method described above.如果我们换一种顺序，将各层重新组合，并且在中间添加一层其他晶体层，会发生什么呢？我们已经知道，氧化物的超导性依赖于层间距离；我们还知道在晶面之间增加一层额外的晶体层，可以将弱导电甚至绝缘材料变为超导体。测试这一想法的真实实验还没有完成，主要是因为，制备原子尺度的“乐高材料”的相关技术仍然处于初期阶段，而且将复杂的多层结构组合到一起也很困难。

目前，这些结构所含的不同晶体层很少能多于5种，一般只含两种或3种不同的晶体层，一般是由石墨烯片与二维材料(绝缘体氮化硼、半导体二硫化钼、二硒化钨等)组成。因为这种堆叠结构含有多种材料，经常被看作异质结构。它们现在的尺寸都非常小，通常长宽都只有10微米，比头发的横截面还小。利用这些堆叠结构，我们可以通过实验来探索其新奇的电学和光学性能以及新用途。这些结构还有一个有趣的特性：它们不仅非常薄，还非常柔软，而且透明。这就为制备多种形状的发光设备提供了可能：研究人员有机会制备出可折叠的显示屏，当使用者需要大一点的显示屏时，就可以将显示屏展开；也可能制备出新的计算机芯片，耗能要比现在的芯片低很多。

研究人员在研究这类新材料时，如果能有一些重大突破，我们相信，一定会发展出相应的大规模制备技术，以实现其工业应用。就像石墨烯和其他一些二维晶体材料那样。最初制备那些材料时，仅能得到几微米大的微晶，现在我们已经可以得到几百平方米大的片状材料。

目前，还没有人发现这类新材料有什么改变世界的“杀手级应用”，然而，这一领域取得的进步，已经让很多科学家感到兴奋。新材料的发现总是会促进人类文明的进步。这是推动人类社会从石器时代到青铜时代，再到铁器时代，最后来到硅时代的背后力量。纳米尺度的“乐高积木”代表了人类从未制造过的新材料。现在，我们只能猜想未来的一切，但我们相信，这种新材料带来的可能性将是无限的。

声波充电

2011年，美国宾夕法尼亚大学，当时还是古生物学专业高年级学生的梅瑞狄斯•佩里(Meredith Perry)伸手去拿她的笔记本电脑充电器。

突然间，一个想法跃入了她的脑海：是否有一天能抛开这些麻烦的充电线呢？她随即开始寻找将这个想法变为现实的途径。

佩里了解到，已经有基于磁共振和电磁感应的无线电力传输技术了，但它们的传输距离有限。限制它们的是平方反比定律(inverse square law)，即电磁辐射的强度与辐射源的距离的平方成反比。

然而，机械振动却不存在这个问题。使用压电转换器从空气中获取振动能量，就可以将机械能转化为电能，这看起来是一个更好的主意。因为声音其实就是振动的空气粒子，所以从理论上来说，它应该能够传输能量。而安全、安静且高能的超声波是个完美的选择。

当佩里同本校教授以及其他专家讨论时，很多人都认为这个想法不可行，因为无法利用超声波提取出足够的能量来为电子设备充电；而且，如果她真要尝试的话，还会遇到大量的电子工程和声学方面的问题。“但是，我知道这在理论上是可行的，”佩里说，“而且没有人能提出足够的证据，证明这绝对无法实现。”所以，她找到了uBeam公司，来研发这项技术。

目前，他们已经开发出了uBeam发射机的原型样机。它相当于一台定向扬声器，可以将超声波聚焦，产生一个能量“焦点”；与电子设备相连的接收器负责接收这股能量，并将其转化为电能。她计划在两年内推出第一批产品。

佩里说，通用无线充电系统不仅能让我们不用再携带目前各式各样且互不兼容的电线和充电器，还可以保证移动设备在进行高耗电操作时不会用尽电量。摆脱电线的束缚，还能带来崭新的室内装修设计思路。此外，目前载有沉重输电线缆的飞机、汽车、太空船等运载工具，重量也可以大幅降低。

“总的来说，无线充电技术将彻底改变我们与物质世界的作用方式，”佩里说，“我们将不再受制于电源插座。”

储存热能的电池

基于热耦合效应的新型电池，可以将白白流失的热能转化为电能，这一技术拥有巨大的应用前景。

在工业生产中，每年都有100亿瓦特的电量以热能的形式被浪费掉了，而这些能量足够为1000万户家庭提供照明用电。通过热电效应(thermoelectric effect)，就可以利用温差发电，把这类热能转化为电能。但是，这样也只能利用其中的一部分。麻省理工学院的博士后研究员杨远(Yuan Yang)解释道：这是因为几十年来的研究都表明，需要达到500℃以上的温差，才能产生出具有实际使用价值的能量。不幸的是，据美国环境保护局(Environmental Protection Agency)的估计，在美国每年浪费的能量中，有三分之一都是以低于100℃的温度逃逸掉的。

杨远和他的导师、斯坦福大学的陈刚(Gang Chen)，以及博士后研究员崔屹(Yi Cui)和李硕祐(Seok Woo Lee)一道，研发出了一种温差仅为理论值1/10(低至50℃)的发电技术。这种技术的关键是利用了热耦效应(thermogalvanic effect，与热电效应有类似之处)。在这个过程中，材料整体的温度都随电压而变化，而非仅在电池中产生温度差。研究团队使用不带电的电池芯，配以铜电极，在高温时进行充电，然后再让它们冷却——神奇的事情发生了，电池的放电电压比为它们充电时所用的电压更高。换句话说，用于加热电池的能量被电池以电能的形式收集了起来。

直到近两年，电池电极的效率才达到能将如此小的温差转化为电能的程度，杨远介绍说。而且在实现商业化前，这项技术还需要很多的研究工作来进一步完善。但是，人们迟早会建起由大量电池组筑起的“围墙”，环绕在工厂烟囱或发电厂的周围，将以往白白浪费掉的热能转化为电力。“这一场景非常诱人，”杨远说，“因为被浪费掉的热能随处可见。”

新型聚合物“泰坦”

环保、高强度、可自我愈合、可回收的聚合物，将改变汽车、飞机等诸多行业。

当化学家珍妮特•加西亚(Jeannette García)在最近用过的一个烧瓶里，发现了一块糖果大小的白色材料时，她压根不知道到自己做出了什么东西。这种材料紧紧附着在玻璃上，所以只能用锤子打碎烧瓶才将其取出。但是，当她再次用举起锤子，去敲打这块材料本身时，后者却毫发无损。“当意识到它的有多坚固时，我就知道必须要弄清楚我究竟做出了什么东西，”加西亚说。

加西亚是IBM公司阿尔马登研究中心的科学家。最终，她在几位同事的帮助之下解开了这个谜团。他们发现，这种令人吃惊的材料是一类新型热固性聚合物。这是一类极为坚固的塑料，能用于从智能手机到飞机机翼等众多产品中。虽然在全球每年生产的聚合物中，热固性材料就占到了三分之一，但是它们很难被回收利用。而加西亚发现的新材料(被称为“泰坦”)，是目前为止发现的第一种可回收的、具有工业级强度的热固性材料。

传统热固塑料无法回收重塑，而上述新型聚合物可以通过化学反应进行重新加工。在2014年5月的《科学》(Science)杂志上，加西亚和同事介绍了他们的发现。

预计，全球对耐用且可回收的塑料产品的需求将很快大幅攀升。到2015年，欧洲和日本都将要求厂家在生产汽车部件时，可回收材料的比例要达到95%。“'泰坦'恰恰可以完美地满足这种需求，”加西亚说。此外，她相信这种新材料最终还能推广到更广泛的应用中，包括抗蚀抗菌涂层、给药设备、粘结剂、3D打印、水净化领域等。

“泰坦”还有其他优点。加西亚和同事发现，这种材料还有第二种形态——在低温时，它会呈现出可自愈合、类似凝胶的形态。这种形态被研究人员称为“海德鲁”(Hydro，意为水)。“如果将海德鲁切成两半，再放回一起，它们会立刻互相粘结，”加西亚介绍说。这样，“泰坦”就可以用作粘合剂，或者自修复涂料，其他相关的化学产品也将陆续被开发出来。“(我们发现的)不仅仅是一种新型聚合物，而且还是一种新的聚合物生成反应。”加西亚说。

视力矫正显示屏

在美国，40岁以上的人群中，超过40%的人在阅读时都需要戴眼镜；而对于80岁以上的人群，这一比例更是达到了近70%。“随着年龄的增长，屈光不正(refractive error)对我们日常生活的影响与日俱增，”美国斯坦福大学电气工程学助理教授戈登•维茨斯坦(Gordon Wetzstein)说。

但是，无论框架眼镜还是隐形眼镜，都有不甚理想的地方。举例来说，一个远视的人，在开车时观察交通路况没有任何问题，但在查看速度表或GPS导航的时候就需要戴眼镜了。这种情况下，最好的解决办法是使用视力矫正显示屏，即能根据用户的情况给显示屏“戴上眼镜”，维茨斯坦说。

与麻省理工学院(维茨斯坦曾在这里工作)及加利福尼亚大学伯克利分校的同事们合作，维茨斯坦研制出了这种显示屏。在智能手机或平板电脑的标准高分辨率显示屏的基础上，他主要做了两项改动：一是打印一种低成本的、布满小孔的透明薄膜，覆盖在屏幕上；二是为智能手机或平板电脑编写算法，来判断用户相对于显示屏的位置，并根据他(她)的验光处方来调整投射的图像。当调整过的图像通过显示屏透明薄膜上的小孔阵列时，在软硬件的共同作用下，屏幕上会产生误差，正好同视力误差相抵消，在用户眼中形成清晰的画面。这种显示屏能为近视、远视、散光和其他更为复杂的视力问题提供相应的矫正。2014年8月，在加拿大温哥华举行的计算机图形图像特别兴趣组(Special Interest Group for Computer Graphics)年会上，研究人员首次展示了这项技术。

据维茨斯坦介绍，在少量用户中进行的非正式测试显示，该技术起到了应有的作用，不过还需要更大规模的研究来进一步完善。研究人员还计划开发一种滑动条，用于手动调整显示屏的焦距。维茨斯坦说，对发展中国家的用户来说，这项技术尤为便利，因为在某些地区，获得移动设备要比通过医生处方购买眼镜更容易。

来源：生物医药论坛

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