Chemical Engineering, University of Southern California
3650 McClintock Ave, Los Angeles, CA 90089 zawolkow@usc.edu
Abstract—Advancements in surgery and medicine have made it possible to perform certain procedures with minimal damage to or effects on the patient. Technology such as the femtosecond laser makes it possible to perform such feats on the sub-cellular level or at the nanoscale. This accuracy and precision of the laser has allowed procedures and studies to be performed on the interaction of the femtosecond laser pulse with biological material. The potential applications of the femtosecond laser in nanosurgery are becoming more apparent as a result of such studies. The technology that makes nanosurgery a possible and practical means of surgery may be right around the corner.
Index Terms
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Femtosecond Laser, Nanosurgery, Sub-cellular, Photodisruption, Ablation
About the Author: Danny Zawolkow is a junior who is majoring in chemical engineering, with an emphasis in Nanotechnology here at the University of Southern California. He is also an active member of the Greek system.

Even though laser technology has existed only fifty-some years it is astounding to see the wide array of applications of this technology that exist today. The range of applications that have developed cover every imaginable category from scientific, military, medical, and industrial, to even commercial uses. The application of laser technology in the medical field has led to breakthroughs in surgical techniques that are used in various types of surgery, including general, refractive, dental, and cosmetic surgery. With developing technologies and ongoing research in laser medicine it is currently possible to perform surgical tasks on the sub-cellular level, more commonly known as nanosurgery. A specific type of technology that is key to making nanosurgery possible is the femtosecond laser. A femtosecond laser is an infrared laser that works at a wavelength of around 1 nanometer, or nm. To put this in perspective a typical human eye can see visible light wavelengths from a range of 390-750 nm.
The laser emits ultra short laser pulses at one-billionth of a second, making surgery possible that is much more precise than surgery performed by human hands.
Femtosecond lasers allow both organic and inorganic materials to be cut with high accuracy and precision with very minimal side effects. The effects of the femtosecond laser are dependent upon the material used and the size, power, and pulse of the laser. The laser is especially valuable in that it can cut tissue very precisely and with practically no heat being emitted to its surroundings. Historically, the femtosecond laser is widely used in ophthalmology, primarily in the LASIK eye surgery, which is done to correct nearsightedness and farsightedness, both-with or without astigmatism [7]. After the success of the femtosecond laser in refractive surgery, researchers investigated the precision and effects of the femtosecond laser surgery on the sub-cellular scale and discovered the great potential for application of the laser in nanosurgical techniques.
The origin of the laser is traced back to the founder of the quantum theory Max Planck. His work on the relationship between energy and frequency of radiation inspired Einstein to develop a theory that made the making of lasers possible.
Einstein theorized that in addition to absorbing and emitting light spontaneously, electrons could be stimulated to emit light of a particular wavelength [9]. The first device to be created based on Einstein’s theory was the maser, created by Charles Hard
Towne in 1954. His ammonia maser was the first to generate and amplify electromagnetic waves, and it inspired the creation of the laser or optical maser. Even though Townes developed the first maser and had plans to develop an optical maser the term laser was first used by one of his competitors Gordon Gould. Gould was the first to use the acronym LASER meaning “light

amplification by stimulated emission of radiation” [9]. Townes was the first to receive the patent for the optical maser, now called the laser, which caused Gould to enter a 30-year patent dispute over the laser. The first successful laser constructed was made in 1960 by Theodore H. Maiman and by 1961 lasers were already appearing in the commercial market.
The technology of the laser soon branched out to the various scientific applications and was medically used first in cell imaging and later in cell surgery. In 1969 a group demonstrated it was possible to perform chromosomal dissection, using an argon laser irradiation with a pulse between 20-30 microseconds. The dissection was possible because of the good quality of the argon laser beam, and because the shorter wavelength could be focused into a much smaller spot than was possible with the multimode emission of the original initial ruby lasers [2]. The application of laser technology to cell surgery, we see that the microsecond pulse, which is one millionth of a second, is long when compared to the duration of a femtosecond pulse. It was only after the introduction of the laser microbeam that researchers began to use short-pulsed laser irradiation with wavelengths in the ultraviolet spectrum that lasted only of a few nanoseconds [3]. With the research in the highly localized effects of ultrashort laser pulses in biomolecules, intraocular surgery soon became possible around the
1980’s [3]. The first femtosecond laser prototypes were built in 1998 and could perform any procedure that was currently done by hand,
Figure 1: Femtosecond Laser Pulse in Eye Surgery using blade or precision surgical instruments, such as mechanical microkeratomes [8] . Soon the laser became widely used in refractive surgery such as the LASIK eye surgery displayed in Figure 1. In the search for even finer results, research was performed to evaluate the effect of the laser on an even smaller range of biomolecules. This eventually led to the current applications of the femtosecond laser in nanotechnology such as nanosurgery or the nanoprocessing of materials.
The laser-material interaction plays a vital role in the understanding of different applications of lasers. The basic interaction mechanisms of light and matter are reflection, refraction, scattering, and absorption [1]. When light comes in contact with a material, the material’s optical properties determine how it interacts with light, depending on the specific wavelength of the light source. The complex structure and chemical composition of materials help determine their optical properties. Optical properties help explain how light interacts with materials, and some of these interactions can be seen by the naked eye, such as what makes objects light, dark, or shiny. The optical properties of human tissue for example are determined by ‘the predominant components: water, hemoglobin, and melanin’ [1]. The exact optical properties can differ tremendously

due to the large variations in and the different locations of the tissues. The optical properties of different biological materials have been continuously studied to determine the best laser parameters for the desired interactions, such as the photoablation or photodisruption of materials. Varying the laser pulse, energy, wavelength, and irradiation time can lead to drastically different effects. When using a laser, it is possible to observe a wide range of interactions, from photochemical, to plasma mediated photodisruption, which is key to the working of the femtosecond laser.
Photochemical interactions can occur from optically activating the cell, thereby triggering a change in specific molecules, an example of which is photosynthesis. Another interaction can be the increase in temperature of the affected area or thermal interactions as they are called. The different thermal effects can be: coagulation, vaporization, and melting which will occur in correspondence to different temperature ranges. Photoablation is the interaction whereby material is removed by laser irradiation. A simple diagram of this process is shown in Figure 2. This can be performed by pulsed or UV lasers, in which the photons directly break the molecular bonds of the material leading to molecular dissociation [1]. The molecules undergo a strong electronic bond breaking resulting in molecular fragments that are carried away from the origin of the laser pulse. Even though the required energy to break the molecular bonds is high there are few thermal effects making this an effective technique in surgery.
Figure 2: Diagram of Ablation
The last interaction is the process of photodisruption. Photodisruption is the process in which rapid ionization of a material causes a shockwave, which creates a small cavity bubble disrupting the area around the ionization. Ionization in this case is the process in which electrons enter an excited state and are ejected from the molecule. Another factor in determining the laser

interaction is the path of light absorption, that path being either linear or nonlinear. Transparent molecules can only absorb light in a nonlinear path making the optical breakdown more difficult. Therefore, when working with transparent molecules, techniques such as the femtosecond laser are required for success.
The process of photodisruption of a transparent biological material explains how the femtosecond laser makes precision surgical cuts such as the creation of the flap in LASIK eye surgery. Transparent biological material does not absorb light by a linear pattern. The femtosecond laser allows for light to be absorbed in a nonlinear process so it can be used with transparent materials. The nonlinear absorption of light causes the electrons to form plasma [5]. The electron density increases until finally plasma is formed from the electrons. This creation of plasma is a key step in the femtosecond laser surgical techniques. The plasma undergoes a ‘temperature to increase rapidly in a very short time scale of a few picoseconds’ [5]. The heated material expands explosively and in the case of an aqueous material a shock wave and cavity bubble will form. The size and extent of photodisruption depend on the amount of deposited energy from the applied laser pulse. The step by step procedure of the femtosecond laser performing in the LASIK eye surgery in Figure 3 explains how the photodisruption inside the cornea is working: [7]
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Figure 3: Photodisruption in the LASIK procedure
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Each laser pulse creates a mini-gas bubble (diameter of 1 micrometer)
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A larger mini-gas/water bubble of approx. 5-12 micrometer diameter appears and separates in the surrounding corneal tissue (photodisruption)
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The emerging mixture of carbon dioxide and water is aspirated, leaving the separated corneal tissue behind.
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Three-dimensional, high-precision laser cuts are created within the cornea by placing thousands of computerpositioned laser pulses next to each other.

The femtosecond laser is primarily used for the flap creation in the cornea prior to the LASIK procedure. The femtosecond laser technique demonstrates a “a smaller more precise incision within the corneal flap allowing faster healing compared to other procedures”[LASIK] The femtosecond laser’s ability to not transfer the heat to the surrounding area results in a safe procedure.
The accuracy and precision of the femtosecond laser photodisruption process surpasses the previous techniques of other surgical precision tools. Doctors report that there are “less complications with femtosecond lasers rather than using other surgical precision tools working at the micro scale” [8].
5.
Being able to work on such a small scale and accomplish individual cell therapy is astounding and indicative of the potential for genetic engineering. Studies investigating the “the mechanisms of the femtosecond laser on biological materials” help establish the technique of nanosurgery on cells and biological tissues [Vogel]. Simply stated, the laser allows the surgery to take place in such a tiny space that it confines and restricts the chemical and cellular reactions. The overall mechanism of this process was explained earlier and the plasma created from the free electrons has a very important and useful property. The free electrons are created below the range of the optical breakdown threshold or the ablation of material. This means that the plasma provides a “tuning range, in which the nature of the laser-induced effects can be deliberately changed by gradually varying the irradiance” [2]. In other words, the creation of plasma creates a cushioning effect to tune the laser for the desired results of the procedure. The different laser-induced effects are utilized in different procedures of nanosurgery. This potential of the femtosecond pulses have been utilized in a variety of functional studies involving ‘chromosome separation during cell division, highly localized DNA damage, measuring the biophysical properties of the cytoskeleton and mitochondria, and even nerve regeneration’ [3]. The success in many studies involving cellular surgery using high-intensity femtosecond laser pulses shows that the ‘application of high-intensity femtosecond laser pulses for cell manipulation studies provides a potential for the investigation of cell-based therapeutics’ [4]. Femtosecond laser pulses make it possible to perform feats such as “transferring foreign DNA into live Chinese Hamster ovarian cells”, a single mitochondrion ablation ‘without compromising the cell’s viability, or even the ‘dissection of an axon in a nerve cell’ [4] [1] [3]. More possible applications include a wide range from surgery, drilling, and even processing of materials on the nano and micro scale.
Clearly, the use of the femtosecond laser as a nanosurgical tool has a wide array of applications and uses. The specific ability of nanosurgery precision without providing thermal damage or shock to the biological environment makes the feats such as the ones listed previously possible. Future research and development of this technology make possible more accomplishments in areas such as nanosurgery, nanoprocessing of materials, nanomedicine, or even genetic engineering.

Having the technology to already perform sub-cellular and nanosurgery is astounding. Seeing the trend of engineering technology on smaller and smaller scales one can only imagine the abilities and applications that new technologies will make possible in the future.
References
[1] Maxwell, Iva “Application of femtosecond lasers for subcellular nanosurgery” ProQuest Dissertations and Theses (PQDT),
2007
[2] A. Vogel, J. Noack, G. Huttman, and G. Paltauf, “Mechanisms of Femtosecond Laser Nanosurgery of Cells and Tissues”
Appl. Phys. B 81, pp.1015-1047. 2005
[3] A. Vogel, J. Noack, G. Huttman, and G. Paltauf, “Femtosecond Plasma-Mediated Nanosurgery of Cells and Tissues” Laser
Ablation and its Applications, vol. 129, pp. 231-280, 2007
[4] V. Kohli, A. Elezzabi, and J. Acker, “Cell Nanosurgery Using Ultrashort (Femtosecond) Laser Pulses: Applications to
Membrane Surgery and Cell Isolation” Lasers in Surgery and Medicine , vol 37, pp.227-330, 2005
[5] A. Heisterkamp, T. Mamom, W. Drommer, W. Ertmer, and H. Lubastschowski, “Photodisruption with Ultrashort Laser
Pulses for Intrastromal Refractive Surgery” Laser Physics, vol 13, pp.743-748, 2003
[6] Cataract and Refractive Surgery Today (2011) Developments of the Femtosecond Laser [Online]. Available: http:///bmctoday.net/crstoday/2010/11/article.asp?f=developments-of-the-emtosecond-laser
[7] LASIK Zentren Gmbh (2007, July 1) iLASIK Precision [Online] Available: http://www.lasikcenter.com/technologie/femtosekundenlaser.html
[8] S. Bolye, (2011) Femtosecond Lasers v Microkeratomes [Online] Available: http://www.northerneye.co.uk/new_page_30.htm
[9] M. Rose, (2010, May) A History of the Laser: A Trip Through Light Fantastic [Online] Available: http://www.photonics.com/Article.aspx?AID=42279
[10] Tanvi Eye Center (2011) Intralase [Online] Available: http://www.tanvieyecenter.com/ser_intralase.html
[11] A. Chen, Green (1998) (Chemistry: Lasers Detect Explosives and Hazardous Waste [Online] Available: http://eetdnews.lbl.gov/nl29/eetd-nl29-3-greenchem.html