History of 

Microscopes
History of Early Light Microscopes

Invention of Glass Lenses

Long before, in the hazy unrecorded past, someone picked up a piece of transparent
crystal thicker in the middle than at the edges, looked through it, and discovered that it made
things look larger. Someone also found that such a crystal would focus the sun's rays and set
fire to a piece of parchment or cloth. Magnifiers and "burning glasses" or "magnifying glasses"
are mentioned in the writings of Seneca and Pliny the Elder, Roman philosophers during the
first century A. D., but apparently they were not used much until the invention of spectacles,
toward the end of the 13th century. They were named lenses because they are shaped like the
seeds of a lentil.

The earliest simple microscope was merely a tube with a plate for the object at one end
and, at the other, a lens which gave a magnification less than ten diameters -- ten times the
actual size. These excited general wonder when used to view fleas or tiny creeping things and
so were dubbed "flea glasses."

Birth of the Light Microscope

About 1590, two Dutch spectacle makers, Zaccharias Janssen and his son Hans, while
experimenting with several lenses in a tube, discovered that nearby objects appeared greatly
enlarged. That was the forerunner of the compound microscope and of the telescope. In 1609,
Galileo, father of modern physics and astronomy, heard of these early experiments, worked out
the principles of lenses, and made a much better instrument with a focusing device.

Anton van Leeuwenhoek (1632-1723)

The father of microscopy, Anton van Leeuwenhoek of Holland, started as an apprentice

in a dry goods store where magnifying glasses were used to count the threads in cloth. He
taught himself new methods for grinding and polishing tiny lenses of great curvature which gave
magnifications up to 270 diameters, the finest known at that time. These led to the building of
his microscopes and the biological discoveries for which he is famous. He was the first to see
and describe bacteria, yeast plants, the teeming life in a drop of water, and the circulation of
blood corpuscles in capillaries. During a long life he used his lenses to make pioneer studies on
an extraordinary variety of things, both living and non living, and reported his findings in over a
hundred letters to the Royal Society of England and the French Academy.

Robert Hooke

Robert Hooke, the English father of microscopy, re-confirmed Anton van Leeuwenhoek's
discoveries of the existence of tiny living organisms in a drop of water. Hooke made a copy of
Leeuwenhoek's light microscope and then improved upon his design.
Charles A. Spencer

Later, few major improvements were made until the middle of the 19th century. Then
several European countries began to manufacture fine optical equipment but none finer than the
marvelous instruments built by the American, Charles A. Spencer, and the industry he founded.
Present day instruments, changed but little, give magnifications up to 1250 diameters with
ordinary light and up to 5000 with blue light.

Beyond the Light Microscope

A light microscope, even one with perfect lenses and perfect illumination, simply cannot
be used to distinguish objects that are smaller than half the wavelength of light. White light has
an average wavelength of 0.55 micrometers, half of which is 0.275 micrometers. (One
micrometer is a thousandth of a millimeter, and there are about 25,000 micrometers to an inch.
Micrometers are also called microns.) Any two lines that are closer together than 0.275
micrometers will be seen as a single line, and any object with a diameter smaller than 0.275
micrometers will be invisible or, at best, show up as a blur. To see tiny particles under a
microscope, scientists must bypass light altogether and use a different sort of "illumination," one
with a shorter wavelength.

The Electron Microscope

The introduction of the electron microscope in the 1930's filled the bill. Co-invented by
Germans, Max Knoll and Ernst Ruska in 1931, Ernst Ruska was awarded half of the Nobel
Prize for Physics in 1986 for his invention. (The other half of the Nobel Prize was divided
between Heinrich Rohrer and Gerd Binnig for the STM.)

In this kind of microscope, electrons are speeded up in a vacuum until their wavelength
is extremely short, only one hundred-thousandth that of white light. Beams of these fast-moving
electrons are focused on a cell sample and are absorbed or scattered by the cell's parts so as to
form an image on an electron-sensitive photographic plate.

Power of the Electron Microscope

If pushed to the limit, electron microscopes can make it possible to view objects as small
as the diameter of an atom. Most electron microscopes used to study biological material can
"see" down to about 10 angstroms--an incredible feat, for although this does not make atoms
visible, it does allow researchers to distinguish individual molecules of biological importance. In
effect, it can magnify objects up to 1 million times. Nevertheless, all electron microscopes suffer
from a serious drawback. Since no living specimen can survive under their high vacuum, they
cannot show the ever-changing movements that characterize a living cell.

Light Microscope Vs Electron Microscope

Using an instrument the size of his palm, Anton van Leeuwenhoek was able to study the
movements of one-celled organisms. Modern descendants of van Leeuwenhoek's light
microscope can be over 6 feet tall, but they continue to be indispensable to cell biologists
because, unlike electron microscopes, light microscopes enable the user to see living cells in
action. The primary challenge for light microscopists since van Leeuwenhoek's time has been to
enhance the contrast between pale cells and their paler surroundings so that cell structures and
movement can be seen more easily. To do this they have devised ingenious strategies involving
video cameras, polarized light, digitizing computers, and other techniques that are yielding vast
improvements in contrast, fueling a renaissance in light microscopy.

A timeline covering the history of microscopes

The definition of a microscope: An instrument for viewing objects that are too small to be
seen easily by the naked eye.

 Circa 1000AD – The first vision aid was invented (inventor unknown) called a reading
stone. It was a glass sphere that magnified when laid on top of reading materials.
 Circa 1284 - Italian, Salvino D'Armate is credited with inventing the first wearable eye
glasses.
 1590 – Two Dutch eye glass makers, Zaccharias Janssen and son Hans Janssen
experimented with multiple lenses placed in a tube. The Janssens observed that viewed
objects in front of the tube appeared greatly enlarged, creating both the forerunner of the
compound microscope and the telescope.
 1665 – English physicist, Robert Hooke looked at a sliver of cork through a microscope
lens and noticed some "pores" or "cells" in it.
 1674 – Anton van Leeuwenhoek built a simple microscope with only one lens to examine
blood, yeast, insects and many other tiny objects. Leeuwenhoek was the first person to
describe bacteria, and he invented new methods for grinding and polishing microscope
lenses that allowed for curvatures providing magnifications of up to 270 diameters, the
best available lenses at that time.
 18th century – Technical innovations improved microscopes, leading to microscopy
becoming popular among scientists. Lenses combining two types of glass reduced the
"chromatic effect" the disturbing halos resulting from differences in refraction of light.
 1830 – Joseph Jackson Lister reduces spherical aberration or the "chromatic effect" by
showing that several weak lenses used together at certain distances gave good
magnification without blurring the image. This was the prototype for the compound
microscope.
 1872 – Ernst Abbe, then research director of the Zeiss Optical Works, wrote a
mathematical formula called the "Abbe Sine Condition". His formula provided
calculations that allowed for the maximum resolution in microscopes possible.
 1903 – Richard Zsigmondy developed the ultra-microscope that could study objects
below the wavelength of light. He won the Nobel Prize in Chemistry in 1925.
 1932 – Frits Zernike invented the phase-contrast microscope that allowed for the study
of colorless and transparent biological materials for which he won the Nobel Prize in
Physics in 1953.
 1931 – Ernst Ruska co-invented the electron microscope for which he won the Nobel
Prize in Physics in 1986. An electron microscope depends on electrons rather than light
to view an object, electrons are speeded up in a vacuum until their wavelength is
extremely short, only one hundred-thousandth that of white light. Electron microscopes
make it possible to view objects as small as the diameter of an atom.
 1981 – Gerd Binnig and Heinrich Rohrer invented the scanning tunneling microscope
that gives three-dimensional images of objects down to the atomic level. Binnig and
Rohrer won the Nobel Prize in Physics in 1986. The powerful scanning tunneling
microscope is the strongest microscope to date.

Types of Microscopes
A compound microscope is an optical device made for magnifying objects, consists of a number
of lenses forming the image by the lens or a combination of lenses positioned near the object,
projecting it to the ocular lens / lenses or eyepieces. The compound microscope is the most
used type of a microscope.

An optical microscope, also called "light microscope", is a type of a compound

microscope that uses a combination of lenses magnifying the images of small
objects. Optical microscopes are the oldest type and simplest to use and
manufacture.

A digital microscope has a digital CCD camera attached to it and connected

to a LCD or a computer monitor. A digital microscope usually has no
eyepieces to view the objects directly. The trinocular type of digital
microscopes has the possibility of mounting the camera that would be a USB
microscope.

A fluorescence microscope or "epifluorescent microscope" is a special type of a

light microscope, instead of light reflection and absorption used fluorescence and
phosphorescence to view the samples and their properties.

An electron microscope is one of the most advanced and

important types of microscopes with the highest magnifying
capacity. In electron microscopes electrons are used to
illuminate the tiniest particles. Electron microscope is a much
more powerful tool in comparison to commonly used light
microscopes.

A stereo microscope, also referred to as "dissecting

microscope", uses two objectives and two eyepieces which
makes it possible to view a specimen under angles to the human eyes forming a
stereo 3D optical vision.

*Most compound types of light

microscopes consist of the
following parts: Eyepiece Lens,
Arm, Base, Illuminator, Stage,
Revolving Nosepiece, Objective
Lenses, and Condenser Lens.
Science Laboratory Tools

Beakers: They are used for routine mixing & heating where a larger opening is more convenient
than a narrow mouth & the greater accuracy of a graduated cylinder is not required. Although it
can be used for measuring, a chemistry beaker is only about 10% accurate & should not be
used for precision measurement.

Graduated cylinders: are useful for measuring out liquids or for calibrating beakers and
Erlenmeyer flasks. They are useful for doing displacement/density measurements as well as
basic volume measuring.

Erlenmeyer flasks: They can be used for general measuring or even juice containers. An
Erlenmeyer flask can be sealed with parafilm or rubber or cork stoppers. They are of similar
accuracy to science lab beakers but less than graduated cylinders.

Watch glasses - Beaker Covers: Watch glasses have all kinds of uses. They can be used as
beaker lids, to hold small invertebrates for viewing under a microscope or to dissolve crystals &
powders. Make an ice lens!

Boiling (Florence) Flasks: The boiling flasks shown in the picture have round bottoms and
need a 4 fingered support clamp and bosshead as shown. The

Flat bottom versions are identical except that the bottom is flat and can stand upright without
support.

Support Stands, Rings and Clamps: These are metal labwares that help support the various
glass equipment.

Dissecting Instrument Kit: This basic dissecting kit is intended for elementary and middle
school use for studying fish, worms, insects and invertebrates

Forceps: The two fine tipped splinter forceps are shown to the left and the medium point
forceps are shown to the right. Thumb dressing forceps are similar to the medium points but are
slightly larger. Tissue forceps (not shown) have teeth on them for an extra firm hold; they are
sometimes known as mouse or rat-tooth forceps.
Common Lab Apparatuses
Laboratory Equipment
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Reading Stone
 Cellular Respiration

Cellular respiration allows organisms to use

(release) energy stored in the chemical bonds of
glucose (C6H12O6). The energy in glucose is used
to produce ATP. Cells use ATP to supply their
energy needs. Cellular respiration is therefore a
process in which the energy in glucose is
transferred to ATP.

In respiration, glucose is oxidized and thus

releases energy. Oxygen is reduced to form water.

The carbon atoms of the sugar molecule are

released as carbon dioxide (CO2).

The complete breakdown of glucose to carbon

dioxide and water requires two major steps: 1)
glycolysis and 2) aerobic respiration.  Glycolysis
produces two ATP. Thirty-four more ATP are
produced by aerobic pathways if oxygen is present.

In the absence of oxygen, fermentation reactions

produce alcohol or lactic acid but no additional
ATP.

Glycolysis:

Glycolysis literally means "splitting sugars." Glucose, a six carbon sugar, is split into two
molecules of a three carbon sugar. In the process, two molecules of ATP, two molecules of
pyruvic acid and two "high energy" electron carrying molecules of NADH are produced.
Glycolysis can occur with or without oxygen. In the presence of oxygen, glycolysis is the first
stage of cellular respiration. Without oxygen, glycolysis allows cells to make small amounts of
ATP. This process is called fermentation.

During glycolysis, glucose (C6) is broken down to two molecules of pyruvate (C3).

Glycolysis occurs in the cytoplasm (cytosol) and does not require oxygen.

There are ten steps in glycolysis and each one is catalyzed by a specific enzyme.

2 ATP molecules are used to phosphorylate and activate compounds that will eventually
become converted to pyruvate (or pyruvic acid) (see diagram below).

Two hydrogen atoms are removed by NAD+ forming 2 NADH.

Additional phosphorylation results in intermediate 3-carbon molecules with 2 phosphate groups.

 Four ATP are produced by substrate-level phosphorylation.
Recall that substrate-level phosphorylation is the production of
ATP using energy from other high-energy compounds but
without the use of the electron transport system in the
mitochondria.

The net yield of ATP in glycolysis is 2 for each glucose

molecule (2 are used but 4 are produced).

Some bacteria have alternative energy-producing reactions.

Two of these are the pentose phosphate pathway and the
Entner-Doudoroff pathway.

During glycolysis, glucose (C6) is converted to two pyruvates

(C3).

C-C-C-C-C-C  C-C-C + C-C-C

The Citric Acid Cycle:

The Citric Acid

Cycle or Krebs
Cycle begins after
the two molecules
of the three
carbon sugar
produced in
glycolysis are
converted to a
slightly different
compound (acetyl
CoA). Through a
series of
intermediate
steps, several
compounds
capable of storing
"high energy"
electrons are
produced along
with two ATP molecules. These compounds, known as nicotinamide adenine dinucleotide
(NAD) and flavin adenine dinucleotide (FAD), are reduced in the process. These reduced forms
carry the "high energy" electrons to the next stage. The Citric Acid Cycle occurs only when
oxygen is present but it doesn't use oxygen directly.

When acetyl CoA attaches to a C4 molecule in the Krebs cycle, the Coenzyme A is released.
Two acetyl CoA molecules are consumed to produce 4 CO2, 2ATP, 6 NADH and 2 FADH2. The

ATP molecules are produced by substrate-level phosphorylation.

Electron Transport:

Electron Transport requires oxygen directly. The electron transport "chain" is a series of electron
carriers in the membrane of the mitochondria in eukaryotic cells. Through a series of reactions,
the "high energy" electrons are passed to oxygen. In the process, a gradient is formed, and
ultimately ATP is produced.

Maximum ATP Yields:

In summary, prokaryotic cells can yield a maximum of 38 ATP molecules while eukaryotic cells
can yield a maximum of 36. In eukaryotic cells, the NADH molecules produced in glycolysis
pass through the mitochondrial membrane, which "costs" two ATP molecules.

References:

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%20respiration/[Link]

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Cell Reproduction
Introduction

     One of the main ideas in the modified cell principle is that new cells arise from pre-existing
cells (Omnis cellula e cellula). Every new cell formed must inherit not only the nucleus which
contains the genetic information, but also should inherit the cell organelles that are required to
express this genetic information. This process occurs by division of the pre-existing cell and is
called cell reproduction or cell division. In spite of the enormous diversity in organisms, the
mode of cell division is essentially similar indicating the Unity of Life.

Cell Division

     Cell division forms a mode of reproduction in unicellular organisms. In multicellular

organisms it is responsible for embryonic development and growth of the adult organism. It is
also involved in repair and regeneration. Both asexual and sexual reproduction requires cell
division.

Cell Cycle

     Every cell that is

capable of
undergoing division
passes through a
cyclic sequence of
events involving
growth and division.
It is called Cell
Cycle. It
encompasses the
entire sequence of
events that occur in
a cell from the time it
is formed from its
parent cell till the
time of its own
division into daughter
cells.
Types of Cell Reproduction:

Three types of cell reproduction are compared: the relatively simple Binary fission and two more
complicated types that either involve mitosis or meiosis.

Binary fission

Organisms such as bacteria typically have a single chromosome . At the start of the
binary fission process, the DNA molecule of the cell's chromosome is replicated, producing two
copies of the chromosome. A key aspect of bacterial cell reproduction is making sure that each
daughter cell gets a copy of the chromosome. Cytokinesis is the actual physical separation of
the two new daughter cells.

Eukaryotic organelles such as mitochondria, chloroplasts, and peroxisomes also

reproduce within the eukaryotic cell by binary fission. How they are allotted to one descendant
cell or the other during mitosis and cytokinesis is not yet clear

Mitosis

Most eukaryotic organisms like humans have more than one chromosome. In order to
make sure that a copy of each chromosome gets segregated into each daughter cell, the
spindle apparatus is used. The chromosomes are moved along the long thin microtubules like
trains moving along train tracks. Humans are diploid; we have two copies of each type of
chromosome, one from the father (red) and one from the mother.

Some human somatic cells are frequently replaced by new ones and other cells are
rarely duplicated.  Hair, skin, and fingernails are replaced constantly and at a rapid rate
throughout our lives.  In contrast, brain and nerve cells in the central nervous system are rarely
produced after we are a few months old.  Subsequently, if they are destroyed later, the loss is
usually permanent, as in the case of paraplegics.  Liver cells usually do not reproduce after an
individual has finished growing and are not replaced except when there is an injury.  Red blood
cells are also somewhat of an exception.  While they are being constantly produced in our bone
marrow, the specialized cells from which they come do not have nuclei nor do the red blood
cells themselves.

Meiosis

The human sex cells (gametes) are produced by meiosis. For sperm production there
are two cytokinesis steps that produce a total of four cells, each with half the normal number of
chromosomes. The situation is different in the ovaries for egg production where one of the four
sets of chromosomes that is segregated is placed in a large egg cell, ready to be combined with
the DNA from a sperm cell.

The steps in meiosis are similar to mitosis and even have the same names. However,
there is a significant difference in how the chromosomes line up initially. In mitosis,
chromosomes line up individually, while in meiosis, the two chromosomes in each homologous
pair line up next to each other. This pairing process is called synapsis, and the resulting
homologous pair is called a bivalent in reference to the two chromosomes or a tetrad in
reference to the four sister chromatids involved.
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