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3 Light Emitting Diodes (LEDs)

3 Light Emitting Diodes (LEDs)

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Light Emitting Diodes (LEDs)


Table 3.3 Concepts found in semiconductor technology: materials and components. With the exception of the

transistor, the decisive processes in the components take place in a single interface layer between two semiconductors that have been doped differently. The last column indicates the doped layers (simplified)

For example, pure silicon or germanium crystal

With a small portion of another element added

Doping supplies free (conducting) electrons

Missing electrons behave like positive charges

Very thin layer at the boundary between two semiconductors

Electronic switching element

Light source with a narrow spectrum (LED)

Light source with a broad spectrum, high intensity

Light source, monochromatic, temporally coherent

Converts light into electric current for measurement purposes

Like a photodiode, used in photovoltaic applications

Electronic amplifier, switching element










Electron energy

Pure semiconductor

Doped semiconductor

n-doped semiconductor

p-doped semiconductor

Interface layer

Rectifying diode

Light emitting diode

Superluminescent diode

Laser diode


Photovoltaic cell




Fig. 3.8 Light emitting diode (LED)


Fig. 3.7 The functioning principle of the LED. Driven by

an external voltage source, electrons move from the left to

the right through the boundary layer between two semiconductors that have been doped differently. They fall to a

lower energy level and give off the energy difference as a


A light emitting diode transforms electric

energy directly into light. This takes place

via the flow of an electric current through the

boundary layer between two differently doped

semiconductors. The active element radiates

primarily in all directions. The focusing of

the light is accomplished by embedding it in a

reflector, as well as through the lensing effect

of a half-dome exit surface (Fig. 3.8). The LED

light exhibits a narrow spectrum that is typically 20 nm wide and, thus, has a very welldefined color. There are LEDs for a variety of

colors, depending on which semiconductors

are utilized.

By combining luminescent dyes, broadspectrum light is generated that is spread across

the whole visible range (Fig. 3.9, spectrum C).

For this, a diode is needed that produces blue or

UV light (Fig. 3.9, spectrum A), from which a

part excites the dye to emit longer-wavelength

light. For the eye, the combination of blue and

yellow results in white light. With the doping

of various luminescent dyes, a variety of spectra and hues can be produced, including finely

tuned white hues, i.e., various color temperatures. The efficiency lies considerably above

that of an ordinary light bulb and is comparable

with that of a fluorescent tube (Table 3.2).



accessible eye. Indeed, the very first application

of the laser in medicine is seen as Campbell’s

intervention.5 At the time when the first lasers

were being developed, no one was able to imagine the multitude of applications that would arise

in the following decades. Today, in ophthalmology, both special surgical instruments as well as

highly developed imaging systems are based on

the laser. The properties of laser radiation, as discussed in Sect. 1.7, contribute to the multifaceted

success of laser applications in ophthalmology.

Their success is also attributed to the variety of

various laser types that work in the desired wavelength range depending on the application. In

addition, pulsed operation gives the possibility to

achieve very high power densities and, thus, trigger various interactions between the laser light

and the tissue. In a continuous mode, the radiated

power is constant and relatively limited, as with a

laser pointer. In pulsed operation, the laser internally stores up the engendered light energy and

then releases it abruptly, a process that repeats

periodically. All laser types are based on the same

physical principle, which is discussed below. In

Chap. 7, we will consider specific laser types that

are applied in ophthalmology, along with the

associated interactions between the laser beam

and various materials.








Wavelength (nm)


Fig. 3.9 Principle of white LEDs. (A) Spectrum of a blue

LED. (B) Fluorescence spectrum (yellow). (C) Spectrum

of a white LED derived from the combination of the primary blue light with the radiation of the embedded luminescent dyes


Light Sources


Shortly after the laser was born (1961), experimental medical applications began. Not surprisingly, the first deployments involved the optically

How Laser Light Is Created:

The Principle

In terms of the lowest common denominator, the

laser as light source is based on a two-step process: first – as with every light source – energy is

added to the atoms of a suitable medium from the

outside, followed by the release of this energy as

light in a very special form in a sort of chain reaction. In the case of the very first laser, the ruby

laser, the chromium atoms in a ruby crystal were

the agents. The focused energy of a flash lamp

transferred blue or green light energy to them,

bringing their electron shells into an excited state.

Normally, excited electrons release their energy


Campbell is mentioned in Sect. 7.1.

3.4 Lasers


within nanoseconds as photons that fly off in random directions, and the associated atoms return

to their ground state. With chromium atoms

within an aluminum oxide lattice (ruby), this

release is somewhat delayed and these atoms are

then said to be in a so-called “metastable” state.

With some atoms, however, spontaneous emission of their photons occurs.

What happens when one of these photons collides with an excited atom? In 1916, decades

before any application, Einstein found the

answer: if the energy of that photon corresponds

to the energy difference between an excited

atom’s energy and its energetically lower state,

the atom is forced to release an identical “copy”

of the stimulating photon. Both photons are identical in energy since both stem from the transitions between the same energy levels and, in

addition, have an identical flight direction.

Einstein called this process stimulated emission

(Fig. 3.10). Now there are two identical photons





Fig. 3.10 A basic process in the interaction of light with

matter: stimulated emission. A photon forces an excited

atom to return to a lower energy state immediately by

emitting a further, identical photon. As in spontaneous

emission (Fig. 2.4), the atom falls into an energetically

lower state and gives off the energy difference as a photon.

After the stimulated emission, both photons have the same

energy, flight direction, and phase

Fig. 3.11 Stimulated

emission produces a chain


that can, in turn, trigger the release of further

photons from neighboring excited atoms. It is

easy to imagine that this process can become a

sort of chain reaction when many atoms have

been brought into an excited state (or, in lasers

that operate continuously, are continuously

brought into this state). This chain reaction,

based on stimulated emission, is the basic phenomenon of a laser. Stimulated emission is the

third basic process of light interaction with matter (after absorption and spontaneous emission,

Figs. 2.3 and 2.4).

Figure 3.11 illustrates this cascade: among

all the excited atoms, one spontaneously releases

a photon and returns to its ground state. This

photon carries exactly the energy difference

between the two atomic states. In another excited

atom, this photon stimulates the emission of an

identical photon. Now, two photons with the

same energy are present. In the next step, these

stimulate two further atoms to emit their photons, and so on. Note that all of the photons

carry the same energy: the energy difference

between the two atomic states. In accordance

with the law of stimulated emission, they all

have the same flight direction. These photons

form the laser light.

To build a functional laser, parallel mirrors at

both ends are necessary. The mirrors send the

photons back and forth, creating a very intense

light field and increasing the feasibility of the

stimulation processes. In this way, the lasing process is supported for those photons that move

precisely perpendicular to the two parallel

mirrors. The laser light that is perpendicular to

the two mirrors is, thus, built up as it travels back

and forth. The exiting beam from the laser arises



Light Sources

Fig. 4-1





Fig. 3.12 Left: The elements of a laser. The two ends of the ruby rod are made into parallel mirrors, the one on the right

reflecting incompletely. P pumping energy source, LM lasing medium, M mirror. Right: Realization as a ruby laser

3.03 eV


Energy (eV)

via the fact that one of the two end mirrors does

not reflect with 100 % efficiency but lets a certain

amount of light pass through (outcoupling). The

two mirrors form a resonator for the light that

travels back and forth. The name indicates that

the arrangement selects the particular wavelength

that fulfills the resonance requirements, whereby

an integral number of half wavelengths must correspond to the length of the resonator. In this way,

one or more very narrow spectral lines are engendered. The construction principle of a laser and

its essential elements are shown in Fig. 3.12.

In ruby lasers, only the chromium atoms are

involved in the lasing process. Ruby is a variety of

corundum (Al2O3) with a small amount of chromium (typically 0.05 %). Figure 3.13 shows the

processes that take place in chromium atoms.

The laser light arises via stimulated transitions

of the electrons from energy level E1 to E0.

The energy difference E1 – E0 of this transition

determines the wavelength of the laser light.

The supplied energy (pumping) takes place via blue

or green light from the flash lamp. This brings the

atoms into an excited state; i.e., it raises the electrons to energy levels E2 or E3, from which spontaneous transition to the state with energy E1 occurs.

The lasing process commences only when

the pumping power exceeds a certain threshold.


2.22 eV E2




410 nm


1.79 eV


560 nm


694.3 nm



Fig. 3.13 Energy level scheme for a chromium ion in a

ruby crystal. Optical pumping with the flash lamp brings

the electron from its ground state at energy E0 to either

level E2 or level E3. From there, a spontaneous transition

occurs to the metastable level E1. From there, a return to

the ground state is induced, with the emission of a photon.

g emitted photon. The energy and wavelength of the laser

radiation is determined by the energy difference E1 – E0

It must be powerful enough to ensure that, despite

the competition of the spontaneous emissions,

level E1 is better populated than level E0 (so-called

population inversion). To understand this prerequisite, we have to keep in mind that, for the light

that is already present in the lasing medium, two

processes can occur: either absorption by atoms

3.4 Lasers




Fig. 3.14 Inversion as the prerequisite that the probability

of stimulated emission exceeds the probability of absorption. This assumes sufficient pumping power. (a) In thermal equilibrium, the lower level is more populated. The

probability is higher that an arriving photon will be

absorbed than that it will trigger a stimulated emission. (b)

Inversion. Powerful pumping leads to a greater population

at the higher energy level. The probability that an arriving

photon will trigger an induced emission is larger than that

it will be absorbed. This means amplification of the light:

from one photon, there are now two

(a) The active medium can be solid, liquid, or gaseous.

(b) The wavelength can lie in the infrared, visual,

or ultraviolet range of the spectrum.

(c) For many types of lasers, the pumping takes

place optically, whereas, with semiconductor

lasers, on the other hand, it occurs directly via

electric current.

(d) The energy output can be continuous with

low power or in pulsed mode operation with

correspondingly short pulses with high power

densities, thereby qualitatively influencing

the kind of interaction taking place between

the light and the target (see Chap. 7).


at lower energy levels or stimulated emission

with atoms at higher energy levels. The relationship of the numbers of these two processes is

given by the ratio of the numbers of the atoms

in the two possible states (E0 and E1). The light

that is already present, thus, experiences both

amplification (via stimulated emission) and

attenuation (via absorption). Amplification prevails when the upper level is filled more than the

lower one (Fig. 3.14). This explains why the lasing process takes place only when a population

inversion is present. In a thermal equilibrium,

e.g., in the hot interior of the sun, the situation

is precisely reversed according to the laws of

statistical thermodynamics: the upper levels are

always less populated. Thus, the sun can never

turn into a laser. Thermodynamics,6 as a basic

principle of nature, says this still more directly:

out of the maximum disorder of a thermal equilibrium, a state of higher ordering (as is the case

with population inversions and laser light) cannot arise spontaneously.


Laser Types

Following its invention, numerous lasers were developed that differ from one another in various ways.


More precisely, the second law of thermodynamics.

Semiconductor Laser

Similar to light emission in LEDs, the light from

semiconductor laser diodes (LD) arises via the

passage of electrical current through the interface layer between variously doped semiconductors (Fig. 3.15). In contrast to LEDs, mirrored





0.3 mm

Fig. 3.15 The structure of a semiconductor laser. Electric

current flows through the interface layer between two

semiconductors (p, n). The lasing process occurs within

this interface (shown in red). Light is emitted in a cone.

The end surfaces are mirrored (M)



end surfaces form a resonator in which a lasing

process takes place, bringing into play the principle of stimulated emission just as with the other

laser types. With semiconductor lasers, extreme

miniaturization is possible. Typical dimensions

are 1 × 1 × 0.1 mm with an exit surface 1 mm

high and 5–200 mm wide. Applications today

are widespread (CD players, laser printers, laser

pointers, etc.).


The Excimer Laser

Argon fluoride (ArF) is a two-atom molecule that

is in an energetically excited state but then decays

into separated Ar and F molecules after a photon

has been sent off (Fig. 3.16). The pump mechanism consists of creating ArF molecules in a mixture of Ar and F gases by means of electrical

sparks. This is the principle of the so-called excimer7 laser. Before the first laser was operating,

Houtermans8 had already pointed out the possibility of this type of laser. Basov succeeded in


Ar F


Fig. 3.16 Potential scheme of ArF: energy as function of

the distance of the two nuclei. Upper curve: unstable

bound state of the ArF molecule. Lower curve: Ar and F

atoms separated spontaneously; total energy lower than in

the bound state



The name is derived from “excited dimer.”

Fritz Houtermans (1903–1966), German physicist.

Digression: Technical History

of Lasers

At the beginning of the 1950s, Einstein’s discovery of stimulated emission was technically

implemented, not with visible light but with

microwaves that have wavelengths 104 times

larger. This laser predecessor, called the maser,9

was constructed in 1954 by the American

physicist Charles H. Townes, who was searching for an ideal amplifier for radar signals. He

used the transition between two energetically

neighboring states of the ammonia molecule

(vibrations of the nitrogen molecule through the

plane of the three H atoms) and could thereby

engender coherent microwaves with a wavelength of 12.7 mm. In 1964, Townes received

the Nobel Prize for physics, along with the two

Soviet physicists, Nicolai Basov and Aleksandr

Prokhorov, who had also independently come

up with the theoretical foundations for the maser

and laser principles.


Distance (nuclei)


building the first experimental one a decade later.

The ArF laser emits ultraviolet radiation at a

wavelength of 193 nm. It is known in ophthalmology for its application in photorefractive corrections (see Sect. 7.3).

193 nm


Light Sources

Superluminescent Diodes


Superluminescent diodes have a structure that is

similar to laser diodes, although no lasing process takes place. These components differ from

semiconductor lasers in the absence of the two

mirroring surfaces (i.e., no resonators) so that

the light can exit directly from the interface layer

without repeated back-and-forth movements.

Through the high population of the excited level,

an amplification of the light takes place via stimulated emission but without a true lasing process. In this way, the SLED achieves considerably


MASER, acronym for microwave amplification by

stimulated emission of radiation.


Superluminescent Diodes (SLED)


Table 3.4 Comparison of LEDs, SLEDs, and LDs. The coherence concept is explained in Chap. 1


Optical spectrum

Beam direction

Light intensity

Temporal coherence

Spatial coherence

Light emitting diode (LED)

Spontaneous emission

Relatively narrow (20 nm)

All directions (~90ent. This method, the

so-called “in situ hybridization” (ISH), utilizes

the fact that complementary DNA (cDNA) binds

to RNA in the corresponding tissue. If the DNA is

labeled (by either radioactivity or fluorescence),

then it can be detected (Fig. 15.8).

To compare the gene expression in two groups

of tissues or cells, we can use the method of “sub-


Fig. 15.8 In situ hybridization to visualize an mRNA of

interest [in this example of connective tissue growth factor

(CTGF) in a subretinal membrane]. Dark-stained purple

areas indicate CTGF mRNA expression. (From Meyer P,

et al. (2002) Ophthalmologica, 216. With permission)

tractive hybridization.” From the first group, the

mRNA is used to make cDNA, which is then

labeled. The mRNA of the second group (called

the target mRNA) is then hybridized to the cDNA

of the first group (called the subtractor cDNA).

The non-labeled mRNA molecules representing

differentially expressed genes are then isolated.

An example of the use of this method is in the

comparison of gene expression in leukocytes

from glaucoma patients with those from age- and

sex-matched controls. The gene expression in the

leukocytes of glaucoma patients was, indeed,

shown to be different than that of controls.

If a difference exists between gene expressions

in a particular tissue, the corresponding mRNA

can be quantified with the real-time polymerase

chain reaction (rtPCR) method. This technique is

based on the “polymerase chain reaction” (PCR).

The basic principle of PCR is the quantification

of a specific DNA or RNA after its amplification.

This amplification is achieved by primers (short

DNA fragments) containing sequences complementary to the target region of interest, which are

used along with a DNA polymerase (after which the

method is named) to enable selective and repeated

amplification. As PCR progresses, the DNA generated is itself used as a template for replication,

setting in motion a chain reaction in which the DNA

template is exponentially amplified (Fig. 15.9).




1 min, 94 ˚C


45 s, 54 ˚C


2 min,72˚C


Fig. 15.9 Schematic drawing of the polymerase chain reaction (PCR) cycle. Heat (94-96 °C) is required to break hydrogen bonds (denaturation). The reaction temperature is

lowered to 50-65 °C for about 40 s, allowing annealing of the

primers to the single-stranded DNA template. With the help

of the enzyme DNA polymerase (red), a new DNA strand

complementary to the DNA template strand is synthesized

(extension). In each cycle, the number of DNA strands of is

doubled. The process is repeated for 30–40 cycles

The aforementioned rtPCR allows the quantification of the DNA or RNA of interest.


Therapies Based on RNA

If a specific gene product has an unfavorable

effect or if a beneficial gene product is produced in excessive amounts, it is desirable to


weaken the effect of that particular gene. In

animals, the particular gene of interest can

be “knocked out.” The effect of the gene can

also be reduced by binding the corresponding

gene products (proteins) by antibodies (e.g.,

anti- VEGFs) by blocking the corresponding

receptors (beta-blockers) or by weakening the

effect of the gene at the level of mRNA so that

the gene is translated less extensively. The

application of siRNA to knock-down mRNA

levels is one of the different methods of “gene


Gene silencing can take place at either the transcriptional or the post-transcriptional level. At

the transcriptional level, the environment around

a gene is modified (histone modification), making this gene less accessible to transcriptional

machinery (RNA polymerase, transcription factors, etc.). Post-transcriptional gene silencing

is the result of the mRNA of a particular gene

being destroyed or blocked, thereby preventing


Another method that holds promise for future

therapy is interfering with alternative splicing.

Alternative splicing is the process that leads to

the formation of several different proteins

derived from the same gene. The DNA and corresponding RNA are composed of several socalled “exons” and “introns.” As the introns do

not contribute to protein formation, only the

exons are spliced and reconnected. Since the

exons can be reconnected in multiple different

ways, different mRNAs can result. Alternative

splicing occurs as a normal phenomenon in

eukaryotes. This explains why the number of

different proteins is greater by far than the number

of genes.

An example of a family of proteins generated by

alternative splicing of the primary RNA transcript

15.5 Therapies Based on RNA



5´ UTR

Exon 1

Exon 2

Exon 3

Exon 4

Exon 5

Exon 6


Exon 7



Exon 8



3´ UTR

VEGFxxx Subfamily-pro-angionic Isoform










VEGFxxx Subfamily-anti-angionic Isoform








Fig. 15.10 The splice variants of human VEGF. The

human VEGF gene, through alternative mRNA splicing,

produces different isoforms with different biological activ-

ities. A change in the terminal amino acid (8a to 8b)

changes the activity from pro- to anti-angiogenic. (Modified

after VEGF-splicing. National Library of Medicine)

is the VEGF family. The resulting RNAs code for

different proteins of different lengths of amino acids

(Fig. 15.10). These VEGF isoforms differ in their

biological properties with respect to the activation of

various VEGF receptors. Knowledge of these isoforms potentially allows the development of highly

specific anti-VEGF drugs, which bind to individual


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