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Surgical Oncology (2009) xx, 1e9
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available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/suronc

REVIEW

In vivo microrobots for natural orice transluminal surgery. Current status and future perspectives
Antonello Forgione*
` Granda Hospital, Piazza Ospedale Maggiore 3, Department of General and Endoscopic Surgery, Niguarda Ca 20162 Milano, Italy

KEYWORDS
Natural orice transluminal endoscopic surgery (NOTES); Micro-robots; Endoluminal surgery; In vivo robotic surgery; Cooperative surgical robots

Abstract The possibility to operate inside the peritoneal cavity through small holes performed in hollow organs that is presented by Natural Orice Transluminal Endoscopic Surgery (NOTES) represents a major paradigm shift in general surgery. While this new approach seems very appealing from patients perspectives because it eliminates completely abdominal wall aggression and promises to reduce postoperative pain, it is very challenging for surgeons because of the major constraints imposed by both the mode of access and the limited technology currently available. For this reason NOTES applications at the present time are performed by only a few surgeons and mainly to perform non-complex procedures. While new devices are under development, many of them are trying mainly to simply improve current endoscopic platforms and seem not to offer breakthrough solutions. The numerous challenges introduced by natural orice approaches require a radical shift in the conception of new technologies in order to make this emerging operative access safe and reproducible. The convergence of several enabling technologies in the eld of miniaturization, communication and micro-mechatronics brings the possibility to realize on a large scale the revolutionary concept of miniature in vivo co-operative robots. These robots provide vision and task assistance without the constraints of the entry incision and have been shown in experimental settings to possess many qualities that could be ideal to partner with Natural Orice Surgery. This article explores the current status of microrobotics as well as presents potential future scenarios of their applications in NOTES. 2008 Elsevier Ltd. All rights reserved.

Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00
* Tel.: 39 0264442503; fax: 39 64442905. E-mail address: forghy@inwind.it 0960-7404/$ - see front matter 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.suronc.2008.12.006

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A. Forgione Robotics in surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . In vivo microrobots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . First generation of in vivo microrobots for gastrointestinal applications . . . . . . . . . . . . . . . . . . . . . . . . . . In vivo microrobots for robot assisted surgery and NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . In vivo multiple cooperative microrobots: an ideal solution for NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . Future perspective of microrobotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The economic advantageous characteristics of in vivo microrobotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Uncited reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00

Introduction
Mans got to know his limitations Clint Eastwood (USA). Natural orice transluminal endoscopic surgery (NOTES) represents a very appealing method for accessing the peritoneal cavity as it leaves no abdominal incisions with potentially complete abolishment of postoperative pain [1]. However, the very nature of this approach means it is limited by the size and physical constraints of the natural orices as well as the subsequent transvisceral access conduit. The limitations of the conventionally available endoscopic platforms also introduce major technical challenges that up to now have limited the application of such approaches to less complicated procedures both in experimental and preliminary clinical applications [2e4]. In particular because the instruments must be long and almost completely exible in order to be inserted through natural orices and reach the surgical eld, they allow only limited force transmission, minimal tractionecounter traction and buckle away from their targets when force is exerted. Moreover, because they have been developed to work inside a restricted environment, currently available endoscopes present limited visual eld and illumination (see Fig. 1). Finally xing the exact orientation is difcult and non-intuitive. Furthermore, the lack of triangulation between the imager and the tools restricts the surgeons ability to judge depth and thereby further limits dexterity [5]. All these technological drawbacks together with the

limited endoscopic expertise of many surgeons are at present limiting the widespread application of NOTES even for basic procedures. The unique challenges presented by the NOTES approach call for a completely new paradigm in the development of new tools. In recent years, much work has been done to develop medical mechanisms and robots in which all (or most) of the devices fully enter the body [9]. These systems represent the result of miniaturization processes in the engineering eld of robotics, micro and embedded controllers, sensor networks, medical and nano-technological research. All these enabling conditions open the possibility to conceive a totally in vivo micro-robotic operating system for advanced natural orice surgery.

Robotics in surgery
In recent years several research groups are investing much effort in the development of new advanced endoscopic platforms that aim to facilitate the performance of NOTES procedures. However judging from experience in experimental settings, it seems that constraints still remain mainly due to the physical nature of the entry site as well as the limited force that can be exerted when using a exible shaft and the necessity to bring together all the visual and working tools (see Fig. 2) [6,7]. In the eld of laparoscopic surgery, robotics has been proposed to overcome the limitations in dexterity introduced by this approach. These systems enhance surgical dexterity through stereoscopic vision, dexterous end-effectors and tremor ltering.

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In vivo microrobots for natural orice transluminal surgery

Figure 1 Design limitations of current exible endoscopes. (a) User-interface too basic to allow easy manoeuvreability. (b) Deployment shaft too exible and therefore prone to looping. (c) Flexible instrumentation prone to tip buckling at site of force exertion inside the peritoneum.

However current surgical robots (such as the Da Vinci system, Intuitive Surgical) have limitations illustrated by most studies which suggest that current robotic systems offer little or no improvement over standard laparoscopic instruments in the performance of basic skills. Currently therefore they have no clear clinical advantages [8]. Current systems remain also constrained by their restricted mobility as well as high cost that limit their availability to few hospitals (see Fig. 3). Moreover, all of the above systems are implemented from outside the body and will therefore always be constrained to some degree by the necessity to work through small incisions (invoking also a fulcrum effect) and the need for additional ports for the introduction of each instrument.

In vivo microrobots
First generation of in vivo microrobots for gastrointestinal applications
First experiences of in vivo microrobots came from the development of technologies to improve endoscopic procedures of the gastrointestinal tract. Typically the endoscope is composed by the head (active part) that incorporates the camera, optics and illumination and by the shaft that allow the advancement of the instrument. By pushing and pulling over the shaft of the device, the endoscope advances inside the lumen however these actions stretch the colon and are at the origin of most of

the pain suffered during the endoscopic examination. Researchers have smartly thought to split the system and make the active part of the endoscope (camera, light) selfpropelling inside the lumen while the control and energy equipment are left outside of the body thus avoiding to stretch the colon so nally limiting the abdominal pain. The control and energy equipment can then be left outside of the body. Many such locomotion developments have been biologically inspired with much focus currently placed on the inchworm method of mobility that uses either a series of grippers and extensors [10,11], multiple legs [12] or inating stents [13] to avoid the generation of excessive traction over mesenteric structures (see Fig. 4). This is intended to minimise the pain that often limits complete examination of the colon such systems have been shown to work properly in experimental settings allowing effective exploration of the entire colonic lumen and in preliminary clinical applications [13]. One more advanced robotic system for in vivo exploration of the gastrointestinal tract is represented by a completely un-tethered camera pill that can be swallowed and naturally moves through the lumen of the GI tract. This commercially available device called PillCam SB (Given Imaging Ltd, Yoqneam, Israel) is a video capsule that measures 11 mm 26 mm and weighs less than 4 g. It contains an imaging device and light-source on one-side and transmits images at a rate of 2 images per second. This generates more than 50,000 pictures over an 8-h period. The images are sent from the capsule wirelessly to a small portable data recorder attached to a belt worn by the

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Figure 2

Selected new endoscopic platforms. (a) The cobra system (USGI). (b) The eagle claw suturing device (Olympus).

patient throughout the examination. Images of the gastrointestinal lumen can be analysed both in real-time for immediate localization of the pill cam or off-line for detailed diagnosis [14] (see Fig. 5). The device has shown to be effective in the diagnosis of several common gastrointestinal disorders, especially for the diagnosis of the origin of obscure or occult bleeding [15]. In recent years several improved versions of the device have been developed in order to overcome some of its initial limitations (i.e. to obtain wider eld of view, better illumination and improved image processing) and to extend clinical applications (e.g. double cameras for diagnosis of oesophageal and colonic diseases and smaller and dissolvable cameras to assess bowel patency and degree of luminal

stenosis [16e18]). At the present time the main limitation of the system is represented by the inability to actively direct the camera pill towards specic targets and the lack of any possible manipulation or biopsy of the intestinal mucosa.

In vivo microrobots for robot assisted surgery and NOTES

The use of miniature in vivo robots that can be inserted into the abdominal cavity during surgery represents a major new direction in robot-assisted surgery. The leading group working on this model of microrobots is that of Prof Dimitry Oleynikow from Nebraska University. Engineers from his

Figure 3 The da vinci robotic system. (a) Console with binocular image presentation allowing 3D high denition visualization. (b) Roticulating instrument tip system (Endowrist) allowing improved dexterity. (c) Cumbersome installation limiting access to the patient.

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In vivo microrobots for natural orice transluminal surgery

Figure 4 Microrobotic systems in development for in vivo use. (a) The inchworm microrobots developed for colonoscopy. (b) Multi-legged microrobots for endoluminal endoscopy. (c) Disposable component of the aer-o-scope system.

team have rstly developed a spring-loaded foldable-tripod platform, the 1-DOF tilting robot that is 15 mm in diameter and 60-mm tall and has an aluminium casing (see Fig. 6). The system includes a permanent magnet direct current

(DC) motor that is used to actuate the tilting mechanism and is controlled by the surgeon from the outside through a switch. The folding tripod base allows the robot to be easily inserted into and removed from the abdominal cavity

Figure 5 (a) The video capsule PillCam. (b) In vivo photograph obtained by the iPill video capsule. (c) Real time visualization (esophageal study).

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Figure 6

Tethered xed in vivo robot (tested for helping during laparoscopic surgery).

through a standard trocar port. This robot allows for rotation about two independent axes allowing it to pan 360 degrees and tilt 45 degrees. This allows the surgeon more in-depth visualization of the abdominal cavity for surgical planning and procedural execution. LEDs provide illumination while the initial prototype was tethered for power. First prototypes of microrobots have also been used in experimental settings for facilitating minimal access surgery. The additional views from the in vivo cameras allow the surgeon to plan and place trocars safely and appropriately in the abdominal cavity of animals [19]. Following this successful experience the same group has developed a more advanced version of a wheeled mobile robot that has the ability to traverse abdominal organs. This robot is 15e20 mm in diameter and 75e100 mm in length. Two helical wheels, independently driven by DC motors, are

designed to provide sufcient traction without causing tissue damage. A tail prevents the robot from spinning but allows it to ip when reversing directions. This 25e50 g robot is capable of producing drawbar forces equal to its weight. This allows it to climb both hilly and deformable terrain as demonstrated during porcine tests. The body of the robot also includes two payload cavities, one of which contains a master microprocessor and telemetry control system (see Fig. 7). The robot also carries an adjustablefocus image sensor to provide real-time video feedback to the surgeon and offers also the capability to perform minimal manipulation and biopsy of internal tissues. This system has been successfully used as the sole source of visual feedback in an experimental setting to perform common laparoscopic procedures and more recently for assisting in the exploration of the peritoneal cavity

Figure 7 Tetherable in vivo robot (tested for providing sole visual feedback during laparoscopic cholecystectomy and for NOTES transgastric procedures).

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In vivo microrobots for natural orice transluminal surgery accessed through a transgastric approach [20]. The latest technological developments have brought a completely wireless version of the same system that has also been shown to work properly in experimental settings. This therefore opens the way to the development of a completely autonomous in vivo system [21,22].

Future perspective of microrobotics

The future is not what it used to be Peter Yogi Bera (USA). While already very interesting, the possibilities offered by the development of in vivo microrobots for application in NOTES procedures also present several further opportunities to envisage. For example, the possibility of equipping microrobots with multiple sensors possessing the ability to monitor in vivo physiological parameters like the temperature, pressure, and relative humidity within the abdominal cavity without requiring any physical connections for power or data transmission has already begun to be explored. An useful application of such features relevant to NOTES procedures could be the facility to alarm the surgeon intraoperatively if any inadvertent tear occurs in the bowel by monitoring changes for instance in the pH of the peritoneal cavity or indeed by the appearance of specic gases due to a leak of the gastrointestinal contents. This opportunity has the potential to greatly improve the safety prole of minimal invasive surgical procedures [23]. Another vision for these types of robotic devices is that they could be easily carried and deployed by non-medical personnel at the site of an injury and then operated by a remote surgeon to provide diagnostic and, ultimately, surgical capabilities moments after injury. For example, historically approximately 90% of battleeld deaths take place within 30 minutes of the initial injury, with 50% of these deaths due to thoracic or abdominal haemorrhage [7]. Wireless in vivo medical robots could signicantly reduce mortality from these injuries by enhancing the ability to deliver rapid therapeutic responses and by providing a platform for continuous physiological monitoring prior to and during transport without cumbersome external connections [24]. One other interesting application under investigation is represented by the development of intelligent microrobots for in vivo targeted drug delivery. For example the Dutch group Philips has developed an intelligent pill that contains a microprocessor, battery, wireless radio, pump and a drug reservoir to release medication in a specic area in the body. The iPill capsule, measures acidity with a sensor to determine its location in the gut, and can then

In vivo multiple cooperative microrobots: an ideal solution for NOTES

The miniaturization of microrobots and the possibility to insert many such robots into the peritoneal cavity through one hole introduces a completely new concept in the development of surgical tools as they allow the assignation of different tasks to separate, independent tools. Furthermore, each device may be super-specialized potentially offering major advances in that each instrument can serve at its best in the performance of any specic task. In contrast, current technological platforms for NOTES are conceived so to bring multiple functionalities inside the same device. Lehman et al. have developed a cluster of collaborative microrobots that can be inserted either through the abdominal wall or natural orices for assisting during minimal invasive procedure and have tested them in an experimental model. The main concept in the design of the devices consists of a stationary outer tube with a rotating inner tube that can alternatively house either lens and camera board, multiple white LEDs or else a grasping device (see Figs. 8 and 9). In order to guarantee stability once inside the peritoneal cavity while simultaneously allowing their independent mobilization, each robot system includes two embedded magnets. One is set at each end of the robot in order that that they may be xed and manipulated by a magnet handle located on the exterior abdominal wall. By changing the position of the external magnetic handle it is possible to reposition the different robot internally allowing improved visualization from multiple angles of the working eld. Organ retraction can also be optimized due to the possibility to use several retracting tools inserted into the peritoneal cavity at once. Experimentally, such a cluster of microrobots has been successfully used to perform a minimally invasive cholecystectomy as well as other procedures [23].

Figure 8 Camera, lighting and retraction robots for minimally invasive surgery (note the depiction of the external magnet applied to allow stabilization of intraperitoneal robot on the peritoneal surface).

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Figure 9 Imaging, lighting and retraction robots as viewed by separate endoscope during in vivo cooperative microrobotic procedure.

release drugs where they are needed. This device has been conceived to treat digestive tract disorders such as Crohns disease. Directed delivery of drugs to the precise location of the disease means doses can be lower thereby reducing side effects [25]. We can imagine that, in the future, the same concept can be adopted for the delivery of high dose of toxic chemotherapeutic agents to intra-abdominal sites without inducing systemic side effects. The implementation of novel visualization miniature technology like confocal endomicroscopy (which allows subsurface histological diagnosis at a cellular and subcellular level in vivo and immediate differential diagnosis between neoplastic and inammatory lesions) into microrobots could also provide the possibility to further direct drug delivery or provide other sorts of ablation therapies [26]. While cooperative microrobots, embedded or not with in vivo sensors, will potentially offer endless advantages to minimally invasive and NOTES surgical procedure, they also however introduce unique challenges for surgeons due to human limitation in coordinating multiple active and inactive objects and in rapidly processing large amount of information. For this reason, together with the process of miniaturization and implementation of sensors, there is a major trend towards cutting edge research eld for equipping microrobotics systems with articial intelligence for autonomous coordination and reaction to changing working environments [27e29].

The economic advantageous characteristics of in vivo microrobotics

With an overall cost of around one million US dollars (to which we must also add running costs per procedure due to the reusable materials plus the maintenance costs) the Da Vinci Robotic system has been considered too expensive for the relatively small technical improvements it offers. Furthermore, strong evidence of relevant clinical advantage is limited. In fact apart from allowing a better articulation of instrument tips and steady camera holding and organ retraction, the Da Vinci robotic system has not brought a real breakthrough in the eld of minimally invasive surgery. Typically also such basic tasks tend to be performed in university and teaching hospitals by young assistants in training that learn through this process while in private clinic more economic auto static devices or indeed scrub nurses are utilized. If we put all those features together we understand why robotics in the eld of general surgery hasnt yet hit the target and is still considered by many nice, but not really essential, tool. In vivo microrobotics however have the potential to impact the eld of minimal invasive surgery and NOTES in a completely and unprecedented way. First of all technical challenges introduced by this natural orice approach cannot be overcome by standard devices. In this sense in vivo microrobots will be enabling tools. Second by their

Figure 10 Schematic representation of a possible scenario for the utilization of endoluminal cooperative microrobots in ambulatory settings under condition of conscious patient sedation.

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In vivo microrobots for natural orice transluminal surgery nature these small tools will be handly, friendly, easy to use, and cheap (especially if we exclude the early phase of introduction). The enormous advancements in micro technology and also the cultural change that is happened in the technological community have already brought in to creation open source basis for systems development. This potentially offers great opportunity to many research groups to work for the development of overall systems by focusing on highly customized micro tools. This overcomes another major limitation of the preceding robotic era that is restrictive patenting due to the almost monopolist position acquired by companies now dominant in the medical robotic market. The result should be a robust and costeffective way to mass-produce robots for many different, specic applications. Moreover, while the Da Vinci robotic system has tended to be used to overcome particular difculties encountered during certain highly complex procedures (but that are often of limited overall incidence), we have to consider that the likely target application of NOTES will be the interventional treatment of high impact disease like acid reux and obesity. Finally, the opportunity to use microrobots introduced through natural orices for endoluminal treatment of common diseases may obviate the need for general anaesthesia and even perhaps sterility. This will enable ambulatory surgery and encourages further diffusion of such concepts (see Fig. 10).

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Conclusions
NOTES has the potential to abolish the historical association of surgery with scars and pain and so represents a major paradigm shift in medical history. To allow performance of advanced procedures and for its widespread application, there is considerable need for a completely new set of surgical devices developed by means of innovative approaches. Today, the availability at low cost of several enabling technologies makes it possible to build innovative platforms based on the revolutionary concept of in vivo cooperative microrobotics. These platforms embedded with in vivo physiological tele-monitoring features and remote controls will also enable hitherto unforeseen scenarios in both emergency care and remote surgery in standard as well as harsh environments. The onset of NOTES associated with technological convergence is therefore paving the way to a completely new way to conceive and perform interventional therapies with great benet potentials for patients as well as health care systems.

References
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Please cite this article in press as: Forgione A, In vivo microrobots for natural orice transluminal surgery. Current status and future perspectives, Surgical Oncology (2009), doi:10.1016/j.suronc.2008.12.006