Introduction

Historically surgery was macrosurgery. Some branches of surgery such as ophthalmology and otorhinolaryngology started to miniaturize early and start using microsurgery. In the last quarter of 20th century, miniaturization started to develop most branches of surgery including neurosurgery. The basic feature was minimization of trauma to the body tissues during surgery. Trends were small incisions, laparoscopic surgery by fiberoptic visualization through tubular devices, vascular surgery by catheters and microsurgery under operating microscopes to refine the procedures and reduce trauma. Many of the devices such as robotics and implants will be a part of this miniaturization process.

Minimally invasive surgery using catheters

Surgery is continuously moving towards more minimally invasive methods. The main driver of this technical evolution is patient recovery: the lesser the trauma inflicted on the patient, the shorter the recovery period. Minimally invasive surgery, often performed by use of catheters navigating the vascular system, implies that the operator has little to no tactile or physical information about the environment near or at the surgical site. This information can be provided by biosensors implanted in the catheters. Verimetra Inc is developing such devices. Nanotechnology will play an important role in the construction of miniaturized biosensing devices. These sensors improve outcomes, lower risk and help control costs by providing the surgeon with real-time data about:

• Instrument force and performance
• Tissue density, temperature or chemistry
• Better or faster methods of preparing tissue or cutting tissue
• Extracting tissue and fluids

Examples of procedures and applications where such an approach would be useful are:

• Cardiovascular surgery
• Stent insertion
• Percutaneous transluminal coronary angioplasty
• Coronary artery bypass graft (CABG)
• Atrial fibrillation
• Cardiac surgery in utero
• Cerebrovascular surgery
• Surgery of intracranial aneurysms
• Embolization of intracranial vascular malformations

Nanorobotics

Robotics is already developing for applications in life sciences and medicine. Robots can be programmed to perform routine surgical procedures. Nanobiotechnology introduces another dimension in robotics leading to the development of nanorobots also referred to as nanobots. In stead of performing procedures from outside the body, nanobots will be miniaturized for introduction into the body through the vascular system or at the end of catheters into various vessels and other cavities in the human body. A surgical nanobot, programmed by a human surgeon, could act as an autonomous on-site surgeon inside the human body. Various functions such as searching for pathology, diagnosis and removal or correction of the lesion by nanomanipulation can be performed and coordinated by an on-board computer. Such concepts, once science fiction, are now considered to be within the realm of possibility. Nanorobots will have the capability to perform precise and refined intracellular surgery which is beyond the capability of manipulations by the human hand.

Nanoscale laser surgery

 Femtosecond laser systems

Scalpel and needle may remain adequate instruments for most surgery work and biological compounds may still be needed to prod cells to certain actions. Introduction of lasers in surgery more than a quarter of century ago has already refined surgery and experimental biological procedures to enable manipulations beyond the capacity of the human hand-held instruments. Mechanical devices such as microneedles are too large for the cellular scale, while biological and chemical tools can only act on the cell as a whole rather than on any one specific mitochondrion or other structure. Further developments are leading to manipulation of cellular structures at the micrometer and nanometer scale. This opening up the field of nanoscale laser surgery.

Femtosecond (one millionth of a billionth of a second) laser pulses can selectively cut a single strand in a single cell in the worm and selectively knock out the sense of smell. One can target a specific organelle inside a single cell (a mitochondrion, e.g., or a strand on the cytoskeleton) and zap it out of existence without disrupting the rest of the cell. The lasers can neatly zap specific structures without harming the cell or hitting other mitochondria only a few hundred nanometers away. It is possible to carve channels slightly less than 1 micron wide, well within a cell's diameter of 10 to 20 microns. By firing a pulse for only 10 to 15 femtoseconds in beams only one micron wide, the amount of photons crammed into each burst becomes incredibly intense: 100 quadrillion watts per square meter, 14 orders of magnitude greater than outdoor sunlight. That searing intensity creates an electric field strong enough to disrupt electrons on the target and create a micro-explosion. But because the pulse is so brief, the actual energy delivered into the cell is only a few nanojoules. To achieve that same intensity with nanosecond or millisecond pulses would require so much more energy the cell would be destroyed

That opens the door to researching how cytoskeletons give a cell its shape, or how organelles function independently from each other rather than a whole system. The technology might be scaled up to do surgery without scarring or perhaps to deliver drugs through the skin. Near-infrared femtosecond laser pulses have been applied in a combination of microscopy and nanosurgery on fluorescently labeled structures within living cells (Sacconi et al 2005). Femtolasers are already in use in corneal surgery.

Femtolaser neurosurgery

Understanding how nerves regenerate is an important step towards developing treatments for human neurological disease, but investigation has so far been limited to complex organisms (mouse and zebrafish) in the absence of precision techniques for severing axons (axotomy). Femtosecond laser surgery has been used for axotomy in the roundworm Caenorhabditis elegans and these axons functionally regenerated after the operation (Yanik et al 2004). Femtolaser acts like a pair of tiny "nano-scissors", which is able to cut nano-sized structures like nerve axons. The pulse has a very short length making the photons in the laser concentrate in one area, delivering a lot of power to a tiny, specific volume without damaging surrounding tissue. Once cut, the axons vaporize and no other tissue is harmed. The researchers cut axons they knew would impair the worms' backward motion. The worms couldn't move backwards after surgery. But within 24 hours, most of the severed axons regenerated and the worms recovered backward movement, confirming that laser's cut did not damage surrounding tissue and allowed the neurons to grow a new axon to reach the muscle. Application of this precise surgical technique should enable nerve regeneration to be studied in vivo.

 References

 Sacconi L, Tolic-Norrelykke IM, Antolini R, Pavone FS. Combined intracellular three-dimensional imaging and selective nanosurgery by a nonlinear microscope. J Biomed Opt 2005;10:14002.

Yanik MF, Cinar H, Cinar HN, et al. Neurosurgery: Functional regeneration after laser axotomy. Nature 2004;432:822.

Copyright © 2005 Professor K. K. Jain