Cryo-EM sees real atoms! Does it look like what science predicts?

All matter on Earth is made up of atoms, which are the smallest units that form the properties of matter. The smallest hydrogen atom has a diameter of about 10^-10 meters, or 0.1 nanometers, or one billionth of a meter; the mass of a hydrogen atom is about 1.674*10^-27 kilograms, and 100 trillion atoms can be arranged on the tip of a needle.

How did people's understanding of atoms evolve from conjecture to theory, and now to the actual sighting of atoms? Do the atoms we see today match the past theories? Let's take a look.

The history of the development of the understanding of atoms As early as more than 2,500 years ago, scientists in ancient Greece had the concept of atoms. This concept was proposed by the ancient Greek materialist philosopher Leucippus and developed and improved by his student Democritus. Democritus' basic description of atoms is:

Atoms are the origin of all things; their fundamental characteristics are fullness and solidity, that is, there is no gap inside, they are solid, impenetrable and indivisible; atoms are eternal, immortal, and infinite in number; atoms are always in a state of motion, and their form of motion is vibration; atoms are extremely small and cannot be seen by people, cannot be perceived by the senses, and can only be understood through reason.

These understandings are only at the philosophical level and are a kind of conjecture, but many of them are consistent with the scientific principles that have been discovered today, such as matter is not infinitely divisible, atoms are the smallest unit, atoms are always in motion, etc. However, there are also many that do not conform to later scientific discoveries, such as fullness and solidity, impenetrable and indivisible, immortal, and infinite in number.

But it was already very precious to know these 2,500 years ago. Our ancient ancestors believed that matter was infinitely divisible, that is, if you cut a one-foot-long stick in half every day, it would never run out. Atomic theory was a big step forward from this conjecture, showing the beginnings of science. Later, ancient Greece really became the earliest birthplace of world science.

Since Democritus proposed the atomic theory, there has been no major progress for more than two thousand years. It was not until the 17th century that many scientists began to confirm the existence of atoms through a large number of experiments and gradually began to understand the true nature of atoms.

In the early 19th century, British chemist John Dalton first proposed the atomic model with modern scientific significance, which has three core points: 1. Atoms are indivisible particles; 2. Atoms of the same element have the same properties and mass; 3. Atoms are tiny solid spheres and cannot be divided.

The greatest achievement of Dalton's atomic model is that it revealed the phenomenon that each element contains only one type of atom, and various atoms combine to form compounds; but the statement that atoms are indivisible and are solid spheres is no different from Democritus's.

British physicist Joseph John Thomson discovered the electron and first proposed the atomic model in 1904, which negated Dalton's "solid sphere model". Thomson's model is called the "date cake model" or "raisin cake model", and some call it the "watermelon model".

Thomson believed that an atom was a ball with a positive charge and that electrons were embedded in the atom, like dates in date cake, raisins in raisin cake, or watermelon seeds in watermelon.

The core of its theory has two points: 1. Electrons are evenly distributed throughout the atom, as if scattered in an ocean with uniform positive charge, and the negative and positive charges of electrons cancel each other out; 2. When excited, electrons will leave the atom and produce cathode rays.

The greatest achievement of this theory is the discovery of the substructure of atoms, and that electrons will leave atoms when excited, breaking the barrier that atoms are solid spheres that are unbreakable and indivisible.

But soon, Thomson's theory was overturned by his student Ernest Rutherford. In 1911, Rutherford proposed the "planetary model" of the atom, the main core of which is: 1. Most of the volume of the atom is empty, and the core is a very small nucleus, which occupies almost all the mass of the atom and carries all the positive charge; 2. The electrons are negatively charged and revolve around the nucleus in a certain orbit, just like the planets revolve around the sun.

This theory is very close to the real appearance of atoms, so it has a profound and lasting influence. Many older people learned this theory when they were young, and many illustrations or propaganda paintings of scientific things still use this model, with an atomic nucleus in the middle and several dots running around the atomic nucleus, forming beautiful cross orbits.

But this model was actually denied by the emerging quantum mechanics a long time ago. The core idea of ​​quantum mechanics is the wave-particle duality of particles, which obeys the uncertainty principle. That is to say, the movement of particles has the properties of probabilistic wave functions, and its position and momentum cannot be determined at the same time. In this way, electrons cannot move in an orderly manner like planets around the sun, but electrons randomly appear at any position around the nucleus, thus forming the electron cloud model of the atom. See the figure below:

These theories analyze the inner nature of atoms layer by layer, and seem to be getting closer and closer to the truth. However, these theories are obtained through experiments and theoretical deductions without seeing the atoms. So, what are real atoms like? Will they be consistent with the theory?

How do humans see the microscopic world layer by layer? Human eyes need light to see matter. It is when light shines on an object and the object reflects, scatters and diffracts the light that people can see. In ancient times, people used their naked eyes to see the world, and the distance and size of objects they could see were greatly limited.

Of course, since many objects are large and bright, the human eye can also see very far away. For example, we can see the moon and stars. The closest of these celestial bodies is about 400,000 kilometers away from us, and the farthest is hundreds or thousands of light years away. The farthest galaxy that can be seen is the Andromeda Galaxy, which is 2.54 million light years away from us.

But the human eye cannot see an ant 100 meters away from us, nor can it see the mites crawling all over our body, let alone the billions of bacteria and viruses on our palms.

This is because human vision is limited by the ability to resolve. Because all objects must have an angle of aperture to reach the retina through the pupil, the normal human eye can resolve about 1' (arc minute), and the limit resolution of people with excellent eyesight can reach 0.5', and the average resolution is 0.75'.

In layman's terms, at a distance of 25 cm, the minimum distance between two object points that the human eye can distinguish is about 0.1 mm, and the limit is 0.05 mm. This standard is called the clear vision distance.

Both telescopes and microscopes use this principle to magnify objects to the point where they can be distinguished by the human eye. People can then see small objects that were invisible or difficult to see. Telescopes bring distant objects closer, which is equivalent to magnifying them; microscopes magnify nearby substances that are invisible to the naked eye until they can be seen.

The earliest microscope was an optical microscope, which uses a convex lens to magnify and observe objects in the lens. It uses visible light to cause the observed objects to reflect, refract, scatter and absorb, showing the shape and brightness of the specimen, and then through the lens magnification effect, allowing people to observe.

Since then, people have seen many microorganisms, including insects and bacteria that are invisible to the naked eye, which has enabled mankind to take a leap forward in its understanding of the world.

However, optical telescopes have a weakness: the greater the magnification of the convex lens, the more serious the diffraction phenomenon, and the object will be distorted and cannot be seen clearly; on the other hand, because optical microscopes use visible light, the maximum resolution of the light can only reach half the wavelength of the light wave.

Visible light is composed of red, orange, yellow, green, cyan, blue, and purple, with wavelengths ranging from about 780 to 400 nanometers. Therefore, even with the shortest wavelength of blue-violet light, the maximum resolution can only reach 200 nanometers. Among microorganisms, bacteria are about 500 to 5000 nanometers in size, so optical telescopes generally have no problem observing bacteria, but viruses, such as the new coronavirus, are only 100 nanometers in size and cannot be seen.

After decades of experiments and research by many scientists, the maximum magnification of optical microscopes has been determined to be 1600 times. A 200-nanometer object magnified 1600 times is only 0.32 millimeters, which is larger than the minimum resolution of the human eye. However, just like the human eye looking at a 0.32-millimeter object, its structure cannot be distinguished.

Only by finding a new way can we further increase the magnification and see smaller objects.

In 1931, the first electron microscope was born. Electron microscope (EM in English) is abbreviated as electron microscope. Electron microscope does not use visible light to observe objects, but uses electron beam and electron lens (usually electromagnetic lens) instead of light beam and optical lens based on the principle of electron optics to image the fine structure of matter at very high magnification.

According to the de Broglie formula, when the electron momentum of the electron microscope's light source is 100Ve, its wavelength is 0.1225 nanometers. Therefore, the electron microscope can observe objects of 0.2 nanometers, which is 1000 to 2000 times higher than the resolution of the optical microscope. The smallest atomic diameter is about 10^-10 meters, or 0.1 nanometers. The emergence of the electron microscope has made it possible for humans to observe atoms.

Atoms go from blurred light and shadow to visible shape when entering the human retina. According to different needs, electron microscopes are divided into scanning electron microscopes (SEM) and transmission electron microscopes (TEM), as well as atomic force microscopes (AFM), scanning tunneling microscopes (STM), etc.

The main difference between a scanning electron microscope and a transmission electron microscope is whether the electron beam passes through the sample when it is focused and scanned. A scanning electron microscope only scans the surface of the sample, line by line; while a transmission electron microscope projects the electron beam onto a very thin sample, passing through the entire sample. However, their basic principles are to bombard the atoms of the sample with electron beams, scatter and diffract the collisions, and obtain images, which are magnified for human eyes to see.

Atomic force microscopes and scanning tunneling microscopes use probes to observe objects at the atomic level. The latter is more precise to observe and locate individual atoms. However, this type of microscope does not "see" the atoms on the surface, but "senses" them. For example, the working principle of STM is to use a very fine needle tip, very close to the sample surface, to produce a tunneling effect through a biased potential.

This tunneling effect only occurs between a few atoms at the tip and the atoms closest to the tip surface, resulting in atomic resolution. But the atomic image is blurry and unclear. See the picture above:

Scientists combined the transmission electron microscope and the scanning electron microscope to form a scanning transmission electron microscope (STEM), which has both the functions of a transmission electron microscope and a scanning electron microscope. Later, a research team at Cornell University in the United States invented a technology called electron stacking imaging, which was combined with STEM to obtain atomic imaging magnified 100 million times.

This is the first time that humans have obtained a relatively clear image of an atom. See the picture below:

In the 1970s and 1980s, cryo-electron microscopy, which achieved a revolutionary breakthrough in the field of microstructure observation, emerged. This technology is based on the ultra-low temperature freezing sample preparation and transmission technology of scanning electron microscopy (Cryo-SEM), which can realize direct observation of liquids, semi-liquids and samples sensitive to electron beams, such as biological and polymer materials.

In 2017, three scientists, Jacques Dubochet, Joachim Frank and Richard Henderson, won the Nobel Prize in Chemistry for their contributions to cryo-electron microscopy biomolecular imaging technology, which has promoted revolutionary breakthroughs in the microscopic world.

In May 2020, two scientific teams from Cambridge, UK and the Max Planck Institute for Biophysical Chemistry in Germany used cryo-electron microscopy technology to obtain the clearest atomic-level photos to date and identified individual atoms in proteins for the first time.

The British team obtained a very complete 1.2*10^-10 meter (0.1 nanometer) structure, using equipment and technology to distinguish individual hydrogen atoms in the protein and surrounding water molecules; while the German team obtained a 1.25*10^-10 meter structure of apoferritin protein. See the figure below:

At this point, the true appearance of atoms is presented before people. Although it is still only the appearance of atoms, you have to know how small this substance is. It is so small that billions of them can be arranged on the tip of a needle. Being able to distinguish them demonstrates the shocking results of science and technology.

Will we be able to see the internal structure of atoms in the future? The advent of electron microscopes and the continuous advancement of science and technology have finally allowed people to see what atoms look like. From the outside, atoms are indeed a bright spot in constant motion, just like the electron cloud model described by quantum mechanics. So, will humans be able to further see the internal structure of atoms in the future?

We know that atoms are indivisible in chemical reactions and are the smallest unit of matter that maintains its basic properties, as is the case with the 118 elements known today. However, atoms can be divided through physical methods, such as through high temperature, high pressure or high-speed collisions, which can cause atoms to fission or fuse and thus become new elements.

Through various experiments, it has been confirmed that atoms are composed of atomic nuclei and electrons, and atomic nuclei are composed of neutrons and protons, and each neutron and proton is composed of 3 quarks. Neutrons are composed of two down quarks and one up quark, and protons are composed of two up quarks and one down quark.

The up quark carries 2/3 positive charge, and the down quark carries 1/3 negative charge. Therefore, the positive and negative charges of the quarks in the neutron are equal, and they are not electrically charged; while the proton has an extra charge due to the positive and negative charges canceling each other out, so it shows 1 positive charge; the electron carries 1 negative charge. In this way, there will be as many electrons as there are protons in the nucleus, and the atom will exist neutrally.

So, will we be able to see these structures clearly in the future, or discover deeper structures inside quarks? According to current theories, it is unlikely.

Because according to the uncertainty principle of quantum mechanics, the deeper the tiny structure, the more difficult it is to determine the kinetic energy and position, which applies to the uncertainty principle; and any observation requires the use of light sources, including electrons and high-frequency and ultra-short wavelength light sources such as X-rays and gamma rays, which will interfere with the tiny structures, making them impossible to see clearly.

In the universe, there are individual protons or neutrons, as well as electrons and positrons, which can be detected by various instruments. They can also be detected in high-precision equipment and instruments such as hadron colliders or accelerators. However, these detections can only be carried out through methods such as bubble chambers to obtain their paths. It is unlikely to really "see" their "appearance".

Moreover, according to the quark confinement theory, the total color charge of quarks is zero, and quarks cannot exist alone due to the strong interaction force. Therefore, under the existing theory, being able to see the appearance of atoms is already the limit, and it will only become clearer and clearer in the future.

However, there is a string theory that says our world is originally composed of 10 dimensions, and the other 6 dimensions have curled up and cannot be seen, so our current world is a four-dimensional space-time, that is, three-dimensional space and one-dimensional time. The smallest unit that makes up this world is not an atom, nor a point-like particle such as a quark, electron, photon, or neutrino, but a tiny linear "string".

These "strings" have "open strings" with endpoints and "closed strings" in a loop. The different vibrations and movements of the strings produce various elementary particles. In other words, the scale of the string is smaller than any particle. This theory is very complicated, so I won't go into details. Many scientists believe that this theory is the most promising model for realizing the grand unified theory.

The so-called grand unification is a theory that unifies the strong force, weak force, electromagnetic force and gravity.

Now the scientific community has unified the strong and electric forces, and the standard model has basically unified the strong, electric, and weak forces. Only gravity is still a mystery. If all particles, including gravitons, are made of "strings", the unification of gravity is a natural thing. Therefore, the scientific community has high hopes for string theory, so it is called the grand unified theory.

If this is true, will humans be able to see the smallest unit of matter, the "string", in the future? According to the uncertainty principle of quantum mechanics, I think this is unlikely. Perhaps a disruptive theory will emerge in the future that can change this expectation.

What do you think about this? Welcome to discuss, thank you for reading.

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