If you get the chance to talk to cell biologists about what they enjoy most about their jobs, you may discover that they’re all microscope geeks, although secretly. At the end of the day, all they want is to sit in a small, dim-lit room for hours on end, communing with their cell type of choice using the lens of a magnificent microscope. That may seem strange, but a cell membrane picture, and cells in general, are spectacular to behold, like living stained glass. 

This level of cellular complexity and beauty is all around us, whether they’re visible to us or not. Cells that are beautifully formed and intricately patterned can be found in just about any plant. They are in the roses in your backyard, in the grass sprouting up through the sidewalk, and even in the carrots you ate in your salad.

Not just plants, either: magnificent layers of cells are embedded in your skin, an insect’s wing, and just about any other living thing you’d cross paths with. We and the world around us are cathedrals composed of cells; we just need a bit of microscopy to appreciate them. 

Microscopes and Lenses

microscopes and lenses

Cells vary in size, but one thing they have in common is they’re all generally small. One good example is a human red blood cell (RBC). A typical RBC is approximately eight micrometers (0.008 mm). To put this in context, the head of a pin is roughly one millimeter in diameter. So about 125 red blood cells may be lined up in a row across the head of a pin. 

Individual cells, with a couple of exceptions, cannot be seen with the human eye. Thus, scientists must study them using microscopes. Microscopes are instruments that magnify objects deemed too small to see and produce an image in which said objects appear larger. Most cell and cell membrane photographs are taken using a microscope. These images are also referred to as micrographs.

From this example, one might think that a microscope is merely a type of magnifying glass. Although, in fact, magnifying glasses indeed qualify as microscopes. Since they only have a single lens, they’re classified as simple microscopes. The fancier ones that we often see have multiple lenses and are called compound microscopes. These lenses can be arranged in a particular manner so they can bend light to produce a more magnified image compared to a magnifying glass. 

So what separates simple, basic microscopes from the powerful machines used in research laboratories? Two factors come into play which are both important in microscopy, magnification and resolution. 

Magnification

It measures how much larger an object appears when viewed through a microscope or a pair of lenses within one. A good example is the light microscopes commonly used in high schools and colleges. They can magnify objects up to 400 times their actual size. So, anything that was 1 mm wide in real life would show up to be 400 mm wide in the microscope image.

Resolution

Meanwhile, the resolution of a microscope or set of lenses is the closest distance between two points that can be separated but still be identified as distinct objects. The lower this value, the higher the microscope’s resolving power. Such microscopes produce images with better clarity and detail. If two bacterial cells were very close on a slide, they might appear as a single, blurry dot under a low-resolution microscope. But, they could be easily told apart using a microscope with high resolving power.

Both parameters are critical to producing a clear image of a tiny object. If one is missing, the result is less than ideal. For example, if a microscope has high magnification but low resolution, you’ll still get a blurry image, only much bigger. 

Electron Microscopy

Having established that different microscopes vary in magnification and resolution, let’s focus on the type that can aid you in peering inside a cell. Electron microscopes are some of the most powerful types of microscopes. They are capable of distinguishing even individual atoms. However, as powerful as they are, they can’t be used to image living cells because the electrons destroy the samples. But recent advancements in electron microscopy have allowed scientists to get a better look.

Recent Advancements in Electron Microscopy

Transmission electron microscopy (TEM) and sealed sample containers that keep cells alive in a liquid environment have made nanoscale-level imaging of living cells a reality in recent years. 

However, it needs to be determined whether the high-resolution images generated with these instruments accurately reflect the structures and functions of cells or whether they only show cells already destroyed by the high-intensity electron beam employed in TEMs. 

So far, there is no means of determining whether the morphological alterations visible in images produced using liquid cell transmission electron microscopy represent the natural state of cells or are the result of radiation damage.

Dynamic Imaging

Transmission electron microscopy generates exceptionally detailed images of cells, revealing features as small as one or two nanometers across. But since the sample chamber of a TEM is a vacuum, samples used in transmission electron microscopy have to be dead or frozen.

Until recently when liquid cell transmission electron microscopy has emerged. The new field allowed scientists to more closely analyze the biological, chemical, and materials science samples in their near-native surroundings. End-users achieve this by immersing the sample in the liquid inside a tiny sealed chamber, which shields it from the high vacuum environment and allows for dynamic imaging.

One drawback of currently-available devices that can be used to hold samples is that they only allow for a lone chamber to be placed under the microscope at a time. As a result, you still won’t know if the images display the unaltered cell or are already damaged by the electron beam.  

Better Beams

Advances in electron microscopy have also resulted from improvements in electron beams. With the use of devices called monochromators, researchers were able to narrow the range of energies for electrons that reach the sample.

To date, they’re already using that tighter energy distribution, together with spectrometers and other devices, to map more-advanced attributes at ever-finer resolutions, moving beyond the basic structure and composition of materials. 

One such target is phonons, which are vibrations in a material’s atomic lattice. Mapping these vibrations at the atomic level reveals a wealth of information about essential processes behind most modern technologies, such as how materials transmit electricity and heat.

The Future of Electron Microscopy

Since the development of electron microscopy, numerous efforts have been made to perform simple imaging of water and other liquids. 

Liquid phase electron microscopy has gradually grown in popularity, with major discoveries advancing the discipline of microscopy. While traditional transmission electron microscopy seeks to provide imaging of thin fixed or vitrified specimens, liquid phase electron microscopy casts a completely distinct approach to study molecules under a liquefied environment.

It’s projected to flourish in the near future with exciting new advancements already underway. With ever-expanding applications in a wide range of fields, liquid electron microscopy is expected to be a valuable analytical tool for solving various molecular and biomolecular-related problems.

 

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