IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL. 4, 2011

Capsule Endoscopy: From Current Achievements to

Open Challenges

Gastone Ciuti, Member, IEEE, Arianna Menciassi, Member, IEEE, and Paolo Dario, Fellow, IEEE

Methodological Review

Abstract—Wireless capsule endoscopy (WCE) can be considered an example of disruptive technology since it represents an appealing alternative to traditional diagnostic techniques. This technology enables inspection of the digestive system without discomfort or need for sedation, thus preventing the risks of conventional endoscopy, and has the potential of encouraging patients to undergo gastrointestinal (GI) tract examinations. However, currently available clinical products are passive devices whose locomotion is driven by natural peristalsis, with the drawback of failing to capture the images of important GI tract regions, since the doctor is unable to control the capsule’s motion and orientation. To address these limitations, many research groups are working to develop active locomotion devices that allow capsule endoscopy to be performed in a totally controlled manner. This would enable the doctor to steer the capsule towards interesting pathological areas and to accomplish medical tasks. This review presents a research update on WCE and describes the state of the art of the basic modules of current swallowable devices, together with a perspective on WCE potential for screening, diagnostic, and therapeutic endoscopic procedures.

Index Terms—Endoscopy of the gastrointestinal (GI) tract, medical robots, passive and active locomotion capsule and vision, wireless capsule endoscopy (WCE).

I. INTRODUCTION

I

N 1868, G. and R. Schindler pioneered methodologies for inspecting the mucosa of the gastrointestinal (GI) tract with semi-flexible endoscopes, paving the way to the advent of endoscopic procedures [1].

Nowadays, traditional endoscopic techniques enable effective and reliable operation through different districts of the GI apparatus, i.e., esophagus, stomach, large bowel or colon and part of the small bowel, with diagnostic, therapeutic and surgical capabilities [2].Flexibleendoscopes,which areintroduced into the oral or rectal orifices, consist of a steerable tip that orients the device toward the regions of interest, by means of cable actuation driven by an external control knob [3]. The rigidity of the instrument, due to the presence of the actuation mechanism running through the whole length of the instrument, and

Manuscript received June 13, 2011; revised September 06, 2011; accepted September 27, 2011. Date of publication October 10, 2011; date of current version January 06, 2012. This work was supported in part by the Intelligent Microsystem Center, KIST, South Korea, and by the European Commission within the VECTOR FP6 European project EU/IST-2006-033970. The authors are with the BioRobotics Institute, Scuola Superiore Sant’Anna, 56025 Pisa, Italy (e-mail: g.ciuti@sssup.it). Digital Object Identifier 10.1109/RBME.2011.2171182

its diameter (from 11 mm up to 13 mm for a standard colonoscope) result in limited accessibility and make endoscopic procedures significantly traumatic and poorly tolerated by patients [4]. Pain or problems with sedation make patients quite reluctant to undergo endoscopy and consistently limits the pervasiveness of a potential mass screening campaign. On the other hand, only mass screening could lead patients to periodically undergo endoscopy with the benefit of discovering and treating asymptomatic pathologies. A further medical drawback of flexible endoscopy is that certain areas of the GI tract cannot be reached, such as most of the small bowel [5].

Thirty years ago, in 1981, G. Iddan conceived a wireless camera pill for imaging of the entire GI tract. Limits in technologies prevented the realization of a swallowable camera capsule, although in the mid 1990s experimental trials were performed on a larger prototype by P. Swain et al. [6].

In the recent past, the availability of low-power and lowcost miniaturized image sensors based on complementary metal oxide semiconductor (CMOS) technology, application-specific integrated circuits (ASIC) and miniaturized light-emitted diodes (LEDs) enabled the realization of swallowable wireless camera pills. In fact, in 2000 Given Imaging Inc. (Yoqneam, Israel), thanks to G. Iddan patents, introduced the wireless capsule endoscopy (WCE) that entails the ingestion of a miniaturized pillsize camera that navigates passively along the GI tract by means of peristaltic contractions, thus visualizing the surrounding wall [7]. WCE enables inspection of the digestive system without discomfort or need for sedation, thus preventing the risks of conventional endoscopy [8]. In this way, WCE has the potential additional benefit of encouraging patients to undergo GI tract examinations [9].

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In 2003, PillCam SB (M2A capsule, Given Imaging Inc.) received approval from the Food and Drug Administration (FDA) and clearance to market capsule endoscopy for use in pediatric patients aged 10 to 18 years, specifically designed for the diagnosis of pathologies of the small bowel. The capsule, provided with a CMOS camera, acquires two images per second and has a battery life of approximately 8 hours [10], [11]. Initially conceived for the investigation of the small bowel, WCE is now spreading to other GI districts. In addition to the M2A capsule, and exploiting similar technology, Given Imaging Inc. produced double-head camera capsules for the inspection of the esophagus (PillCam ESO, Given Imaging Inc.) and of the colon (PillCam COLON, Given Imaging Inc.) [12], [13]. Up until 2009, more than 750,000 patients had undergone WCE in clinical trials, although the sensitivity of capsule endoscopy for the detection of colonic lesions is still low compared to the use of traditional colonoscopy [14].

Several other companies produce endoscopic capsules, such as Olympus Inc. (EndoCapsule, Olympus Medical Systems Corp., Tokyo, Japan), Chongqing Jinshan Science and Technology (OMOM capsule, Chongqing Jinshan Science and Technology, Chongqing, China) and Intromedic Co. (MiRo capsule, Intromedic Co. Seoul, South Korea) [15].

Although WCE has entered the medical scene as a disruptive technology, it presents a number of limitations, e.g., the impossibility to actively control capsulelocomotion andcameraorientation which leads to low diagnostic specificity and to false-positive results, mainly in the colonic tract. Therefore, the natural evolution of WCE consists of integrating mechanisms for active locomotion and also providing the capsule with microsensors and micro-tools for diagnosis and therapy [16]–[18]. In this regard, many research centers and private companies are exploiting mechatronic knowledge and background for the enhancement of WCE capabilities, ranging from simple diagnosticcamerastocompleteand autonomousdiagnosticandtherapeutic robotic platforms.

II. SYSTEM ARCHITECTURE FOR ENDOSCOPIC CAPSULES

The human GI tract is composed of the esophagus, stomach, small bowel and colon. The esophagus consists of a muscular tube through which food passes from the pharynx to the stomach and is approximately 250 to 300 mm long and 10 to 20 mm large in diameter. The stomach is located between the esophagus and the small intestine. It is a deflected elastic cavity characterized by a thick mucous membrane that secretes protein-digesting enzymes and acids. The small intestine is an elastic lumen with villi coating its internal surface; it is 30 to 40 mm in diameter and is the longest portion of the GI tract (approximately 6.5 to 7.5 m in length). The last segment of the GI tract is the large intestine or colon, that is about 1.6 m in length and 60 mm in diameter [28]. Each segment of the GI tract is characterized by different anatomical and physiological properties, thus leading to different challenges for the design of endoscopic capsules.

A complete capsule platform comprises six primary modules: locomotion, vision, telemetry, localization, power and diagnosis/tissue manipulation tools (Fig. 1). However, most capsules developed to date include a subset of the modules described above, of primary importance due to space constraints. Each miniature module represents an engineering challenge per se, however, thanks to current technological progresses in microsystem development, interface and integration, devices can be designed that embed all these modules and that are able to provide both diagnostic and treatment functionalities. Alternatively, a possible solution may be to use several task-specific capsules that operate independently or that are self-assembled into a single operating system [19], [20]. The next sections illustrate the different modules of an endoscopic capsule, with specific focus on the locomotion module (Section II-A). In fact, locomotion is the feature that distinguishes an uncontrolled probe navigating in the bowel from a teleoperated miniature robot performing diagnostic and surgical tasks.

Fig. 1. Illustration of modules of robotic endoscopic capsule: locomotion, vision, telemetry, localization, power and diagnosis and tissue manipulation tools are schematically represented. Courtesy of Virgilio Mattoli.

A. Locomotion: Passive and Active Approaches

Locomotion represents a crucial issue that must be taken into consideration in the design of a wireless endoscopic system. In this regard, WCE can be classified as passive or active capsule endoscopy, depending on the presence (or absence) of a controlled locomotion strategy. Active or passive locomotion also generates different application scenarios both for patients and for the healthcare system, as further detailed below. Passive locomotion exploits the natural peristaltic contractions of the bowel; for this reason, passive capsules, which dominate the WCE market, do not need the direct involvement of a physician during the entire procedure. Peristaltic movements are unpredictable and result in unreliable diagnoses in 20% of the trials [21]. On the other hand, active locomotion, still at research level, has the potential to enhance diagnostic consistency and to allow the endoscopist to control the device when operating in areas of interest [9]; the main drawback regards the difficulty in integrating the locomotion module into the capsule body and keeping the size as low as a couple of cubic centimeters. Active locomotion potentially enables teleoperation. This means that patients from any part of the world may receive excellent medical care and that both patients and physicians may save on unnecessary travel costs [22]. However, active capsule teleoperation entails a different application scenario compared to passive locomotion, since the physician’s presence is required throughout the entire procedure to control the steering of the capsule and to activate therapeutic functionalities.

1) Passive Endoscopic Capsules: In 2000, P. Swain and Given Imaging Inc. announced the advent of the first swallowable camera capsule for the diagnosis of the small bowel, during the Digestive Week Conference in San Diego (California, U.S.) [23]. The capsule, called M2A (PillCam SB, Given Imaging Inc.), represented in Fig. 2(a), is a disposable passive camera pill for the small bowel, with a diameter of 11 mm, a length of 26 mm and 3.7 g in weight [24], [25].

PillCam SB2, Given Imaging’s latest CE device for the small bowel, was produced and approved by FDA in 2007 and is provided with enhanced image and battery features [26]. Given

TABLE I MAIN FEATURES OF CURRENT ENDOSCOPIC CAPSULES In the above table only the commercially available capsules have been included for which all the listed characteristics are available.

Fig. 2. Commercially available camera capsules for small bowel: (a) PillCam SB and PillCam SB2, (b) PillCam ESO and (c) PillCam COLON by Given Imaging Inc., (d) MiroCam by Intromedic Co., (e) EndoCapsule by Olympus, Inc., and (f) OMOM of Chongqing Jinshan Science and Technology Group.

Imaging Inc. also produced the Agile Patency System, a dissolvable and biodegradable capsule of the same size as PillCam SB. The capsule assesses adequate patency of GI tract in patients with suspected strictures (e.g., Crohn’s disease and tumors), thus avoiding risk of retention. The capsule has a 10% dispersed barium in a lactose body, which enables fluoroscopy visualization, and contains radio frequency identification tags to determine capsule location by means of the Agile Patency Scanner and TesTag [27].

Other companies, such as Olympus Inc., Intromedic Co. and Chongqing Jinshan Science and Technology Group, produced the EndoCapsule [Fig. 2(e)], MiroCam [Fig. 2(d)] and OMOM capsule [Fig. 2(f)], respectively. Although each reported commercial capsule is designed for the diagnosis of the small bowel, main differences are related to the image sensor and selected power solution. Table I summarizes the main capsule features, but for a more accurate explanation please refer to Sections II-B and II-E.

Due to the rapid progression of cuds (approximately 10 s), esophageal passive capsules require a high frame rate and need a short battery life. Regarding these design specifications, Given Imaging Inc. produced two versions of an esophageal capsule equipped with two cameras—one at each end: the PillCam ESO [Fig. 2(b)] and PillCam ESO2, respectively [7].

For the anatomical and physiological features of the stomach, no specific passive locomotion capsules were designed purposely for investigating this organ.

Instead, regarding the last segment of the GI tract, due to the larger diameter of colon with respect to the small intestine, the PillCam SB is not appropriate for providing a reliable view of the entire wall: consequently, there is a high risk of not detecting all potentially pathological areas in the lower GI tract. Given Imaging Inc. brought out a colonic capsule, PillCam COLON, that has a length of 31 mm, a diameter of 11 mm and is provided with two cameras, one at each end [10], [29]. PillCam COLON received the CE mark in 2006,but failed to obtain FDA approval in 2008 [Fig.2(c)].Main features of theesophageal andintestine capsule are reported in Table I.

In traditional WCE procedures, once ingested, the pill is carried passively through the GI tract by peristalsis, capturing images of the lumen wall randomly. Before undergoing colonic WCE the patient must go on a liquid polyethylene glycol-based diet and fast up to 24 hours before the examination, likewise in a colonoscopy preparation. For analysis of the small bowel, fasting is required after dinner the night beforehand, and only 4 hours before an esophagus diagnosis. Oral sodium phosphate, an oral prokinetic and rectal suppository are still required for ensuring an effective lumen cleaning, that is essential for promoting capsule locomotion and obtaining clean images. A typical esophagus examination takes about 20 minutes, and consists in the ingestion of the capsule while the patient is laying down on his/her side. Instead, for the small and large intestine, the capsule is swallowed by the patient while standing upright and image data are processed by the physician offline, after few hours (generally around 8–10 hours, which is the battery life time), or also in real time [30].

Although WCE eliminates the drawbacks of traditional endoscopy, it presents some contraindications. In particular,smallbowel WCE is contraindicated for patients who have undergone multiple medical interventions, because suspected obstructions

Fig. 3. Internal locomotion capsules: esophagus capsules respectively developed by (a) Tognarelli et al. and (b) Glass et al.; (c) swimming capsule developed by Tortora et al, for stomach diagnosis; bowel capsules developed by (d) Kim et al., (e) Li et al., (f) Park et al., (g) Valdastri et al., and (h) vibrating capsule produced

by Zabulis et al.

could cause capsule retention [31], [32]. Moreover, WCE in general is considered unsuitable for patients with pacemakers or implanted electromedical devices, due to the risk of mutual interference [33].

2) Active Endoscopic Capsules: Capsules endowed with active locomotion allow direct remote steering and navigation control of the device toward suspicious areas. This also enables therapeutic and surgical procedures to be performed by wireless capsule robots. There are mainly two strategies for providing a swallowable capsule with active locomotion. The first consists of pursuing the miniaturization of locomotion systems that are integrated on-board the capsule, i.e., internal locomotion, while the second in using an external approach where actuation, generally based on magnetic fields, is outside the capsule, i.e., external locomotion.

1. a) Internal Locomotion: Several different internal locomotion strategies have been addressed in literature and the most significant solutions will be presented and discussed below, going through the GI tract from the esophagus to the colon.

In the esophageal tract, active mechanisms have to be developed for decelerating the rapid progression of an endoscopic capsule along its path. In this regard, an endoscopic robotic device with a shape memory alloy (SMA)-based anchoring mechanism has been developed as depicted in Fig. 3(a) [34]. The capsule is featured by three active flexible legs provided with strain gage sensors for measuring the force applied onto the tissue. An on-board actuator controlled by a microcontroller allows the legs to be released and retracted when desired.

A mechanism that ensures the anchoring of capsules to the intestinal wall was presented by Glass et al. [35]. The mechanism consists of three actuated legs with compliant feet lined with micropillar adhesives, which are able to withstand axial peristaltic loads at a fixed location [Fig. 3(b)].

A promising solution for endoscopic capsule locomotion in a liquid-filled stomach was presented by Tortora et al. [36], [37].

The robotic device exploits propellers that are wirelessly controlled by the operator in terms of desired direction and speed [Fig. 3(c)]. Another approach for the development of a submarine swimming capsule was presented by Guo et al. [38], who developed a fish-like S-shape swimming robot with ionic polymer metal composite actuators for both medical and industrial applications.

A number of different internal locomotion approaches, which target the entire intestine (i.e., large and small bowel), have been developed by many research institutes. The mechanism proposed by Glass et al. for locomotion in the esophagus was extended by Karagozle et al. [39] combining two of the presented anchoring modules in the development of an SMA-based six legs endoscopic capsule that mimics a crawling motion.

A bio-inspired earthworm-like intestine robot was presented by Kim et al. [40], [41]; it works with cyclic compression/extension SMA spring actuatorsandwith anchoring systems based on directional micro-needles [Fig. 3(d)]. This solution does not allow for bidirectional and oriented motion, yet the micro-needles provide a passive anchoring mechanism without entailing actuators or power demanding systems.

Another bio-inspired solution exploits a locomotion system mimicking cilia extension. The capsule is composed of six SMA actuated units (each unit with two SMA actuators for enabling bidirectional motion) with two appendages for each unit [Fig. 3(e)] [42].

A promising solution for crawling in the intestine was proposed by Park et al., that consists in a paddling-based technique. The capsule is composed of multiple legs actuated by a linear actuator that travels along the entire length of the capsule. The legs are retracted at the back of the capsule, before recycling at the front, thus allowing direction propulsion [Fig. 3(f)] [43].

Effective leg-based designs were proposed by the BioRobotics Institute of the Scuola Superiore Sant’Anna, demonstrating an active control and anchorage of the capsule, together with an adequate visualization of the lumen without the need for insufflation.

Starting from a preliminary solution based on SMA technology [44], different designs, based on dc motors, have been addressed. In particular, four leg [45], eight leg [46], and 12 leg [9], [47] capsules have been developed, progressively increasing effective locomotion and complete visualization of the lumen [Fig. 3(g)].

Another solution that enhances the propulsion of an endoscopic capsule in the intestine tract is based on a vibratory actuation strategy. A simple mechanism, composed of a motor with an eccentric mass as the rotor, produces the vibration of the capsule, thus reducing friction with the environment. However, this approach has the disadvantages of not ensuring active orientation, change of direction, and capsule fixation [Fig. 3(h)] [48], [49].

Finally, electrical stimulation of the GI muscles is a method that is able to roughly control capsule locomotion or at least stop it by generating a temporary restriction in the bowel [50], [51].

Although internal locomotion has significant advantages, such as local distension of the tissue away from the camera and the lack of interferences due to magnetic field sources, it reveals dramatic drawbacks related to the presence of actuators, transmission mechanisms and high-capacity power modules that lead to excessive internal encumbrance in order to attain the size of an ingestible capsule. A numerical estimation of the energy consumption related to different locomotion strategies will be reported in Section II-E.

1. b) External Locomotion: In order to limit the volume of the capsule’s internal components due to the presence of actuators, transmission mechanisms and power supply modules, capsule locomotion obtained through external propulsion has been approached by many research groups. Magnetic fields that interact with internal magneticcomponentsarenormally used to provide external propulsion. By exploiting externally generated magnetic fields, the internal space of the capsule is increased, thus allowing most of the modules of Fig. 1 to be included in a swallowable system. Electromagnets, as external magnetic field generators, can generate well-controlled magnetic fields although requiring bulkier equipment, if compared to external permanent magnets. A crucial issue in the design of a magnetic locomotion mechanism is the dimensioning of the internal and external magnetic sources necessary for obtaining the required forces and torques for reliable and efficient capsule control in the GI tract [52], [53]. Once the magnetic field allows the capsule to be reliably controlled and held in specific areas, magnetic-based solutions can be exploited for propulsion along the entire GI tract. The following description is mainly focused on the selected magnetic approach (i.e., electromagnets or permanent magnet) with some examples of capsules with external locomotion designed for specific districts.

The Norika Project Team (RF System Lab, Nagano, Japan) has been developing external powered WCE since 1998. The Norika capsule is provided with three internal electromagnets (acting as rotor coils) that interact with three external electromagnets (acting as the stator coils) that are integrated in a vestlike jacket; this configuration allows capsule rotation to be obtained in the GI tract [54].

Fig. 4. External locomotion capsules: Olympus Inc. magnetic capsule concept.

Olympus Inc. has been developing a magnetic active capsule since 2004. The capsule integrates an internal permanent magnet interacting with an external magnetic field generator that consists of three pairs of electromagnets.A rotating external field determines the bidirectional propelling of the capsule that is provided with a spiral ridge around the body (Fig. 4) [55].

Among the different actuation methods, electromagnetic based actuation has also been considered by Yu et al. for 3-D locomotion and drilling tasks of a permanent magnet microrobot in intravascular procedures [56].

A novel magnetic steering technology for gastric examination was developed cooperatively by Olympus Inc. and Siemens Healthcare (Erlangen, Germany). The system includes an Olympus Inc. capsule endoscope (31 mm long and 11 mm in diameter, provided with two 4 frames/s image sensors) and Siemens magnetic guidance equipment, composed of magnetic resonance imaging (MRI) and computer tomography (CT). The capsule is controlled by the physician by means of two joysticks and can be moved in the stomach with five independent degrees-of-freedom (DOF), i.e., 3-D translation, tilting and rotation [Fig. 5(a)] [57].

In 2010, Chongqing Jinshan Science & Technology developed a magnetic robotic platform for capsule steering in the gastric district. The system includes a disk-shaped permanent magnet controller held above an operating bed and an OMOMlike diagnostic capsule provided with on-board permanent magnets [58].

A similar approach was pursued by Given Imaging Inc. as part of the European FP6 project called “Nanobased Capsule-Endoscopy with Molecular Imaging and Optical Biopsy” (NEMO project). A wireless PillCam COLON-based capsule endoscope was modified to include neodymium-iron-boron magnets and was manipulated through a handheld external magnet in the esophagus and stomach. Safety and efficacy of the remote magnetic steering was assessed in in vivo studies paying the way for the enhancement of diagnostic endoscopy as well as enabling therapeutic WCE [59], [60].

Another approach to WCE that takes advantage of active magnetic locomotion in the GI tract combined with accurate driving by an anthropomorphic robotic arm was developed by Ciuti et al. The system combines the benefits of permanent magnets in terms of magnetic field strength together with accurate and reliable control of the magnet through use of a robotic arm [61]. This platform demonstrated to be a reliable solution for

Fig. 5. External locomotion platforms for WCE: (a) gastric examination platform developed cooperatively by Olympus Inc. and Siemens Healthcare, (b) roboticaided permanent magnetic platform developed by Ciuti et al., and (c) GI tract exploration platform developed by Carpi et al., exploiting Stereotaxis system.

moving and steering a capsule in a slightly insufflated intestine in ex vivo and in vivo conditions, with much more accuracy than manual steering of the external magnet [Fig. 5(b)] [62].

A robotic magnetic navigation system (Niobe, Stereotaxis, Inc., U.S.), developed for cardiovascular clinical procedures, was exploited by Carpi et al. and consisted of accurate robotic steering of a magnetically modified video capsule (PillCam, Given Imaging Inc.). In vivo trials were performed in each of the main GI tract regions (esophagus,stomach,small bowel,and colon) in a domestic pig model, and the capsule was tracked in real time through fluoroscopic imaging [Fig. 5(c)] [63].

A critical limitation of all these external magnetic approaches regards effective locomotion and lumen visualization of the capsule in the deflated lumen and mainly in the large intestine.

In order to overcome this problem, Simi et al. developed a wireless endoscopic capsule with hybrid locomotion, as a combination between internal actuation mechanisms and external magnetic dragging. The capsule incorporates an internal actuating legged mechanism, which modifies the capsule profile, and small permanent magnets, which interact with an external magnetic field, thus imparting a magnetic dragging motion to the device. The legged mechanism is actuated whenever the capsule gets lodged in collapsed areas of the GI tract, thus allowing modification of the capsule profile and making magnetic dragging and lumen visualization feasible and effective once again [64].

Another promising solution was proposed by Toennies et al. [65]: a tetherless insufflation system was proposed which is based on a controlled phase transition of a small volume of fluid stored on-board the capsule to a large volume of gas, emitted into the intestine.

B. Vision

The main goal of endoscopy (both traditional and WCE) is to inspect the GI tract using imaging techniques for diagnostic purposes. In addition to diagnostic aims, vision also represents the main feedback for the control of the endoscopic tools and for the performance of effective therapeutic and surgical procedures. For these reasons, image quality is a primary issue in both traditional and innovative endoscopic devices.

Standard flexible endoscopes include light delivery system, imaging camera and additional channels for medical purposes. Light from an external source is carried to the target through an optical fiber bundle and tissue images are transferred back to an acquisition camera located outside the body through coherent optical fibers or a lens system [5].

In capsule endoscopy, a first tradeoff for the implementation of any vision system is between high image quality and other features such as size, power consumption, simple control interface, image resolution and frame rate. The image acquisition hardware, integrated inside endoscopic capsules, consists of an image sensor, illumination, lens and compression chip.

Given Imaging Inc., the major worldwide company in the field of capsule endoscopy, commercializes solutions for different GI tracts, all implementing a fixed focal length CMOS imager with different rate characteristics. The OMOM and MiRoCam capsules mount the same CMOS image sensor technology, while the EndoCapsule uses charge couple device (CCD) technology for the imager (Table I). The specific frame rates for the different capsules are determined in order to optimize the quantity of data needed for diagnosis while the LEDs are lit at each image acquisition in order to reveal the surrounding environment [66].

An ingestible pill-shaped endoscopic capsule, the Sayaka capsule, developed by RF System Lab, integrates a solution for image capturing. While conventional capsules, including the RF System Lab’s Norika capsule [Fig. 6(a)], have cameras at one end of the capsule, Sayaka’s CCD camera is placed in the middle and is continuously rotated by 7.5 steps thus providing approximately 30 frames per second [Fig. 6(b)] [67].

CMOS and CCD are two different technologies that are used for digitally capturing images and mainly differ in integration capability and power consumption. CMOS technology, due to its low-power consumption and high integration capability and controllability, is more suited for small devices than CCD, althoughCCDprovidesahigherimagedepth[68].However,from a clinical point of view, since both technologies provide excellent images of the GI tract, CMOS imagers are more suitable for capsule endoscopy given their low-power and easy-to-integrate features [69].

High specificity and design requirements of capsule endoscopy in terms of image resolution, dimension, sensitivity and power consumption have led research groups to develop novel image sensors. For example, Vatteroni et al. designed a custom CMOS sensor reducing power consumption (less than half compared to off-the-shelf sensors) and enhancing

Fig. 6.   RF System Lab’s (a) Norika and (b) Sayaka capsules.

light sensitivity which makes sensor performance comparable to CCD technology performance for single chip endoluminal applications [70].

Starting from the described chip, a field programmable gate array with a complete wireless imaging acquisition chain, suitable for WCE, was developed as the electronic core of the “Versatile Endoscopic Capsule for gastrointestinal Tumor Recognition and therapy” project (VECTOR project) [71], [72].

Optical lens design is also a crucial step for developing the image acquisition hardware and obtaining high quality pictures. Most lenses in currently available systems are designed for allowing fixed focal length only. An example of autofocus lenses for endoscopic capsules was implemented by Cavallotti et al., who developed a capsule prototype that uses a liquid lens actuated by a pulse width modulated signal to adjust the focal length from 30 up to 100 mm [73].

The image compressor is another important subsystem in the image acquisition architecture; by compressing images, the system can transmit the images telemetrically in order to achieve high frame rate at specific data rate telemetry communication. In fact, collected images contain large amounts of information that have to be compressed to ensure high frame rates, which are mainly required in teleoperated capsule endoscopy with active locomotion. In WCE, the compression system has to take into account power consumption and speed requirements, while retaining sufficient image information for a correct diagnosis. Compression algorithms for capsule endoscopy have been designed by several research groups in consideration of power limitation and available constraints of WCE [74]–[76]. A low-power, low-complexity compressor specifically developed for capsule endoscopy [77] was selected in the implementation of the VECTOR project electronics. This algorithm, implemented on the FPGA digital integrated circuit, is based on integer version of discrete cosine transform and it performs, sequentially, color transformation, image transformation, coefficients quantization and entropy coding operations.

The compressor introduces some artifacts due to the nature of the compression algorithm in tissue observations, but it allows for sufficient image quality for diagnostic purposes [72].

Finally, image analysis software represents an important feature for the optimization and completion of the diagnostic procedure. Given Imaging Inc. and Olympus Inc. equipped the external workstation respectively with the RAPID software suite and EndoCapsule software, for enabling efficient management of capsule endoscopy studies [66]. Useful post-processing software consists of automatic classification and extraction of meaningful diagnostic frames among the entire set of the captured images, which reduces the process time spent by physicians when examining the videos [78].

The SIAS group at the Instituto de Engenharia Electrónica e Telemática de Aveiro (IEETA) (Campus Universitário de Santiago, Aveiro, Portugal) produced CapView and ECCA (Endoscopic Capsule Capview cAtaloguer) software, both compatible withGiven ImagingInc.andOlympusInc.endoscopiccapsules. CapView software is a full suite for endoscopic capsule exams reviewing and report generation, while ECCA software allows the creation of events datasets to be used on computer vision algorithms [79], [80].

On-board capsule software can also implement a lumen detection strategy in order to optimize camera orientation [49] and in situ video analysis for the identification of potential diseases or other interesting features [81]. A lumen detection strategy could also be employed in a magnetic active locomotion scenario, as main control feedback for enabling the automation of endoscopic procedures.

C. Telemetry

Wireless communication is essential in WCE for allowing image streaming and for receiving commands from an external workstation. In WCE, an efficient telemetry system is characterized by high power efficiency and data rate so as to transmit a large amount of high resolution images with low power consumption.

Given Imaging’s capsules exploit a commercially unidirectional available radio frequency (RF) transmitter chip specifically produced by Zarlink Semiconductor Inc. (Ottawa, Canada), with a power consumption of 5.2 mW, a data rate of 2.7 Mb/s and carrier frequency of 403–434 MHz.

Custom unidirectional telemetry systems have been developed by several research groups with different power efficiencies and data rate features [82].

A low-power wireless telemetry system for capsule endoscopy, based on impulse-radio ultra-wideband technology, was developed by Gao et al. The whole system is implemented in a 0.18 m CMOS process and integrated in a single 3 mm 4 mm chip. The transmitter consumes an average power of 2.5 mW at 10 Mb/s data rate and the receiver needs 40 mA current at 1.8 V [83].

A high-speed receiver for capsule endoscopy was proposed and implemented by Woo et al. with a data rate of 20 Mb/s. The receiver uses a 1.2 GHz band to receive RF signal, and demodulates the signal to an intermediate frequency stage (150 MHz). The demodulated signal is amplified, filtered, and undersampled by a high-speed analog-to-digital converter. Thus, in order to decode the under-sampled data in real time, a simple frequency detection algorithm is selected and is implemented using an FPGA circuit [84].

A miniaturized low-power, high data rate transmitter for WCE was developed by Thonè et al. and integrated in the VECTOR project capsule [71]. The telemetry chip transmits at 2 Mb/s with 2 mW of power consumption, using a 144 MHz carrier frequency [82].

An alternative strategy for telemetry in WCE, based on electric-field propagation, was proposed by Intromedic Co. and integrated in the commercially available MiRo capsule [85]. This technology uses the human body as a conductive medium for image data transmission. In order to evaluate the clinical safety and diagnostic feasibility of the capsule integrating this telemetric solution, a multicenter clinical trial was performed for the diagnosis of the small bowel [86].

A telemetric solution for commands in WCE, requiring a lower data rate than telemetry of images, was developed by Susilo et al.; this solution integrates a bidirectional telemetry system based on the ZigBee communication protocol on IEEE 802.15.4 standard [19]. Bidirectional communication is essential for the active locomotion of capsule robots needing to receive control commands. The ZigBee communication protocol is characterized by low data rate, high networking capability and low power consumption. A data rate of 250 Kb/s allows for bidirectional transmission of control signals, although it is not adequate for image data. This solution can be adequate for capsules devoted to in-body parameter monitoring rather than image transmission (e.g., for all capsules reported in Section II-F).

D. Capsule Localization

The development of an efficient localization method represents an important contribution in WCE. In fact, the knowledge of the position and orientation of the capsule allows the localization of lesions and pathological areas to be determined for future follow-up treatment or more accurate diagnosis. Moreover, spatial information defines the distance travelled by the capsule in the GI tract and the anatomical districts in which it is located. Finally, with a perspective to implementing a robotic-aided platform (as reported in [61] and [62]), localization information allows for capsule motion control loop. As a result, several research groups and companies have approached different localization strategies with the aim of detecting the position and orientation of the capsule during its journey along the GI tract.

Radio frequency (RF) triangulation represents a low-resolution localization method, which is exploited by Given Imaging Inc. and is integrated in the PillCam SB systems. The RF localization algorithm is based on the strength of capsule emitted signals received by eight sensors (antennas) on the exterior of the abdomen. Experimental assessments were performed resulting in an average position error of 37.7 mm and a maximum error of 114 mm [87], [88].

Magnetic tracking algorithms were also implemented for obtaining capsule space information. The capsule, provided with an on-board permanent magnet, can be detected by a skin-mounted magnetoresistive sensor array measuring both magnetic field strength and direction. As proposed by Wang et al., the capsule can be localized with an average position error of 3.3 mm and an average orientation error of 3, although the overall accuracy is highly dependent on the number of external sensors used [89], [90].

A similar approach was proposed by Innovent (Jena, Germany) with the 3D-MAGMA magnetic detection system, which exploits 27 magnetic field sensors for collecting individual measurements with a control time loop of 20 ms and an overall accuracy of 5 mm and 2 [91].

Another magnetic sensor-based solution for WCE localization was proposed by Andra et al.; here, a permanent magnet, on-board the capsule, is repeatedly aligned by a vertically oriented pulsed magnetic field. Due to this alignment, the position can be measured by commercial field sensors with a position error of less than 10 mm [92].

A magnetic tracking system was developed by Motilis Medica SA (Lausanne, Switzerland). The Motilis GI motility monitoring system covers the entire GI tract, providing the physician with segmental transit time, 3-D detailed dynamics of progression and motility indices. The coordinates of the magnetic capsule are calculated from signals recorded by sixteen magnetic field sensors allowing for a position error of less than 3 mm [93], [94].

All the above magnetic-based localization strategies are not applicable to the external magnetic locomotion approach (see Section II-A), since the external magnetic field needed for locomotion would dramatically affect the external sensor array measurements. A localization approach, compatible with external magnetic locomotion, was proposed by Salerno et al. The approach is based on a triangulation algorithm able to detect the capsule in the GI tract by recording and processing external magnetic field measurements through a custom on-board tri-axial magnetic sensor [95]. A position error of 14 mm along the X axis, 11 mm along the Y axis and 19 mm along the Z axis were obtained (where X and Y are in the plane of the abdomen and Z is in the vertical direction as regards this plane).

Alternative—but less common—approaches to localization consist of ultrasonic pulses emitted from outside the body and echoed by the internal capsule [96], or of a radioactive agent, placed on-board the capsule and detected externally by Gamma Scintigraphy [97].

E. Power

Power supply is a critical issue in endoscopic capsule system integration. Most commercially available endoscopic capsules integrate silver-oxide coin batteries in the capsule shell that provide for approximately 8–10 hours at a voltage of 3 V at 55 mAh, with an average power delivery of 20 mW. Silveroxide batteries are selected because they are the only kind of batteries approved for clinical use, although they are not the most efficient powering solution. Details about battery life times for commercially available wireless capsules are reported in Table I.

Increasing battery life and power are essential technological goals for the development of active locomotion devices, which integrate both diagnostic or therapeutic functionalities.

A promising solution for power supply is represented by the lithium ion polymer (LiPo) technology. These off-the-shelf rechargeable batteries have a high energy density of approximately 200 Wh/kg, and they are capable of supplying peak currents up to 20 times their normal nominal current. The high power and the small and custom-shaped package make LiPo batteries good candidates for being integrated on-board endoscopic capsules [98].

Miniaturized batteries combining high energy and high power are 3-D thin-film batteries (TFBs). Three-dimensional TFB technology was developed at Tel-Aviv University and licensed to Honeycomb Microbattery (Tel Aviv, Israel) [99], [100]. This battery technology has an energy density larger than 300 Wh/Kg and a maximum pulse current of 500 mA in a battery volume of about 40 mm.

Wireless power transmission of power represents an alternative to on-board batteries. Wireless techniques for transmitting electric power include electric-field induction, radio frequency, microwave radiation and piezoelectric ultrasound systems [101]. In particular, inductive coupling provides wireless energy to the capsule by exploiting internal electromagnetic coils that receive power from an external abdominal coil.

The Norikatechnology exploits the on-board electromagnetic coils used for capsule orientation also for powering the endoscopic capsule by inductive coupling. A coil vest, worn by the patient, allows power transmission and direct control of the device. Similarly to the Norika capsule, Sayaka capsule power is supplied wirelessly from an external source, thus avoiding that harmful battery substances enter the body [67].

A video capsule integrating inductive powering technology was also developed by Lenaerts et al. for in-body applications. An external magnetic field generated by a solenoid coil powers three internal coils on-board the capsule thus providing up to 150 mW [102]. The same approach was extended by Carta et al. for powering several capsules, i.e., propeller-driven and vibratory-actuated prototypes [36], [49]. In these configurations, power transfer was enhanced thanks to the use of a ferromagnetic core within the internal coil module. In the swimming capsule, the inductive power system was able to provide 200 mW, thus supplying four brushed motors, connected to their respective propellers [37]. In the vibratory capsule, a multicoil inductive link was demonstrated to provide over 300 mW without time limitations and regardless of capsule orientation, for powering a brushed motor (290 mW to vibrate at 190 Hz) employed for capsule vibration [48].

An additional improvement could consist of using an electric double-layer capacitor (also called supercapacitor) as energy buffer to provide the high current required for motor activation.

A potential power source could consist of chemofluidic phase transition systems that generate pneumatic pressure. The fluid power concept, initially applied in a prosthetic arm by Goldfarb et al. [103], has the potential to be a lightweight, high power and energy effective technology for WCE also [65].

Power saving can also be achieved by implementing algorithms that can automatically tune the capsule imaging frame rate according to the capsule speed. Finally, the use of nanobiogenerators could exclude the need for batteries, as mechanical energy—such as blood flow, muscle contraction or body movements—could be converted into electric energy for powering in-body devices [104].

F. Diagnosis and Tissue Treatment

The steady progress in the BioMEMS field has generated capsules with sensors, such as pH, pressure, blood detection and temperaturesensors,thusenhancing capsulecapabilitiesandenablingnewtasks.Moreover,tissuetreatmentsystemscanbeintegrated in capsules for providing interventional capabilities, such asdrugdelivery,biopsysamplingorclipreleasetostopbleeding.

In 2008, Given Imaging Inc. acquired the Bravo pH monitoring system from Medtronic (Minneapolis, U.S.). The Bravo system consists of a disposable capsule, temporarily placed by means of an endoscopic procedure in the esophagus that measures pH levels and transmits the data to an external receiver. The pH test is used for the diagnosis of the gastroesophageal reflux disease (GERD) [Fig. 7(a)] [105]. Chongqing Jinshan Science and Technology also produced a pH monitoring capsule system that is used for the prophase diagnosis and anaphase treatment evaluation of GERD disease [66].

Gonzalez-Guillaumin et al. developed a capsule containing sensors for impedance and pH monitoring of the esophagus with wireless communication for the detection and characterization of GERD. Magnetic holding was proposed as an alternative solution to surgical fixation of the monitoring capsule, thus representing an advantage with respect to the Bravo pH monitoring system that requires a metal spike-based attachment to the esophageal wall [Fig. 7(b)] [106].

Body temperature is another important physiological parameter that deserves to be monitored in certain special diagnostic

Fig. 8. Tissue treatment capsules: (a) IntelliCap produced by Philips and (b) wireless therapeutic clipping capsule produced by Valdastri et al.

procedures. The telemetric physiological monitoring system VitalSense (Mini Mitter Co., Inc., Bend, U.S.) consists of a receiver/monitor and a thermistor-based ingestible capsule for core body temperature measurement [Fig. 7(c)]. The CorTemp ingestible core body temperature sensor is a capsule for body temperature monitoring mainly designed to measure heat stress in workers in industrial environments [107].

A wireless multisensor microsystem, comprising temperature, conductivity, pH and dissolved oxygen sensors, a control chip and a transmitter (Lab-in-a-Pill capsule) was developed by Johannessen et al. Sensors were fabricated on two separate silicon chips located at the front end of the capsule; the system can be adapted to biomedical and industrial applications [108].

Recent patents on biosensor solutions for capsule endoscopy have been reviewed by Moglia et al. [109].

Philips Inc. (Philips Electronics Inc., Amsterdam, Netherlands) produced IntelliCap,acapsulesystem whichincorporates a microprocessor, battery, pH sensor, temperature sensor, RF wireless transceiver, fluid pump and drug reservoir [Fig. 8(a)]. The system is able to measure body internal parameters and to deliver a topic treatment pharmaceutical agent on command [110], thus also providing a therapeutic functionality.

Innovative Devices, LLC (Raleigh, U.S.) produced the IntelliSite capsule, a radio frequency activated SMA-based drug delivery device capable of noninvasive controlled delivery of drugs to the GI tract with the localization support of Gamma Scintigraphy. In addition, Phaeton Research (Nottingham, U.K.) proposed the Enterior capsule that allows drug delivery by means of a piston/spring actuation mechanism [97].

Advanced imaging analyses, such as fluorescence endoscopy, optical coherence tomography, confocal microendoscopy, Raman spectroscopy, molecular imaging and light-scattering spectroscopy, represent potential techniques for the implementation of in situ optical biopsy on-board the capsule. Such advanced diagnostic methods go beyond standard diagnostic endoscopic techniques by offering improved image resolution, contrast, and tissue penetration, and providing biochemical and molecular information about mucosal disease through light-tissue interactions. Moreover, standard biopsy requires the removal of about 10 tissue samples (2–3 mm) around the same location and analysis within 1–2 hours from the extraction. For these reasons, the development of a biopsy module integrated in a wireless capsule is extremely difficult [111].

Light-tissue interaction can also be exploited for detecting bleeding in the GI tract. The VECTOR project developed a diagnostic capsule able to detect blood in the intestine using transmission spectroscopy based on an LEDs emission system [71]; likewise, Inoue et al. implemented a blood detection system using a low energy wireless Raman spectrometry to scan for active bleeding or clots along the intestinal wall [112].

Valdastri et al. developed the first therapeutic WCE able to release a clip for treating bleeding in the GI tract or for closing incisions in transluminal applications. The capsule [Fig. 8(b)] is controlled by means of external magnetic fields and provided with a single pre-loaded SMA-based clip, which can be activated wirelessly by control command by the operator. Successfulex vivo and in vivo surgical experiments were performed, paving the way to a new generation of capsule devices capable of performing both diagnostic and therapeutic tasks [113].

A microbiopsy module, as part of a capsule endoscope, was developed by Kong et al. This module, less than 2 mm in thickness and 10 mm in diameter, consists of a rotational razor attached to a torsion spring for cutting tissue in the small bowel. Through dedicated ex vivo experiments, tissue samples were successfully extracted using the proposed biopsy module, although a dramatic drawback is related to the insufficient number of samples that can be collected for an accurate histological evaluation [114].

Innovative therapeutic capsule solutions were presented by Moglia et al., such as ultrasonic-based capsule prototypes proposed by Miyake et al. and Taniguchi et al. [109].

III. WORK IN PROGRESS AND CHALLENGES

To date, commercially available capsules are designed and tailoredto performscreeningproceduresinthedifferentdistricts of the GI tract. This approach is mainly due to the limits of technology development that prevents integration of the required modulesandfunctionalitieswithinaningestiblecapsuletomake it completely versatile for approaching the entire GI tract.

However, the rapid development of miniaturization technologies may allow development of a capsule in the near future, capable of managing all the GI parts, e.g., by combining internal and external locomotion approaches [64]. This trend is reported in most WCE review papers, predicting that in the near future the integration of additional features into the capsule will be feasible, thus allowing diagnostic capabilities and even therapeutic interventions to be performed.

Although the integration of all diagnostic and therapeutic modules on-board a single capsule could be feasible in the future, a more significant and current trend from a clinical perspective is represented by the development of three different types of capsules with different capabilities: screening, diagnostic and interventional capsules.

This approach has been pursued by the VECTOR project [71] with the realization of three capsules, i.e., a screening capsule for GI inspection at low data rate dedicated to asymptomatic patients; a diagnostic capsule for patients with symptomatic diseases; and a therapeutic capsule for delivering treatments (Fig. 9). Compared to a “universal” capsule, the three capsules solution could be more feasible at present in terms of implementation and integration, and more cost effective, since the use of the capsule can be diversified based on medical needs and, when necessary, different capsules can be used in

Fig. 9. VECTOR project capsule concepts, i.e., (a) screening, (b) diagnostic and (c) therapeutic capsule, respectively.

consecutive procedures (starting from the screening capsule up to the therapeutic one). In fact, the screening capsule could be employed in low-cost investigations for asymptomatic patients or in mass screening campaigns; the diagnostic capsule could be used in patients with indications of diseases and/or once the screening capsule has detected potential pathological spots to be investigated in more detail. Once a disease has been correctly diagnosed, therapeutic capsules, with different capabilities, may be exploited accordingly to the treatment that has to be performed (e.g., stop bleeding, biopsy, polypectomy or resection of lesions and drug release).

In addition to the advantages of integrating dedicated therapeutic and diagnostic modules on-board endoscopic capsules, improvements in WCE at research level are mainly related to the integration of active locomotion systems for ensuring reliable control of capsules in the GI tract, and thus avoiding limitations of passive undetermined movements. Owing mainly to the difficulty in further miniaturizing motors and batteries for the implementation of an internal locomotion strategy, external magnetic field propulsion has been approached as the most promising locomotion strategy at medium term. By exploiting external generated magnetic fields, the available space inside the capsule is increased and several modules (Fig. 1) may be potentially included in an ingestible size.

Vision is also an important issue in both traditional and innovative endoscopic devices, as it is the main feedback for diagnosis and for the control of the endoscopic robots in the performance of effective medical procedures. Consequently, high frame rate (up to 24 frames/s compared to the typical 2 to 4 Hz frame rate) and image quality (larger than 1/4 VGA as typical camera resolution of the commercial capsules) have to be pursued as the main requirements in teleoperated active locomotion endoscopy. Moreover, advancements towards this goal are expected to include progressively sophisticated image compression algorithms for fast transmission of high quality images on the telemetry link.

In this perspective, power issues must be considered in order to provide the capsule with active movement, with the ability to stop for close inspection of specific areas and with the possibility of managing image stream and sensors requirements. A potential and promising solution to achieve full potential would be the integration inside the capsule of a wireless transmission power module, e.g., electric-field induction, radio frequency, microwave radiation and piezoelectric ultrasound systems.

A localization system should also be integrated in the capsule (especially in the 3-capsule approach) in order to evaluate the position and orientation of the device for reliable closed-loop control and/or for subsequent intervention with therapeutic modules. Although localization systems are currently at the proof of concept stage, clinical magnetic-based locomotion applications will need to exploit compatible magnetic based localization strategies [95].

Finally, additional functionalities for endoscopic capsules have to be seriously considered during the design of these devices, such as tools for polyps removal, mucosa resection, biopsy and drug delivery (e.g., releasing of medical drug-loaded sheet), in order to make diagnostic capsules competitive with traditional endoscopes.

An important opportunity related to endoscopic capsule research concerns the exploitation of WCE knowledge and technology for the development of medical devices capable of approaching other districts of the human body, even smaller than the GI tract, such as the vascular district. In this perspective, the redesign and downscaling of WCE technologies have to be addressed for approaching smaller human body lumens and probably more adverse conditions; e.g., the device could require a higher sterility and the district could be totally or partially closed, thus requiring strict constraints as regards locomotion control. The relevance of this new research field is confirmed by the contributions brought by several research groups working in the development of medical platforms for vascular procedures. Promising solutions were presented by Martel et al. and Belharet et al. with the development of clinical magnetic resonance navigation-based platforms for the steering of artificial or synthetic untethered micro-devices and microrobots in endovascular procedures [115], [116]. Another example of manipulation of microrobots in human body cavities was presented by Kummer et al., who developed an electromagnetic system (OctoMag system) for five-degree-of-freedom wireless magnetic control of an untethered microrobot for intraocular delicate retinal procedures. This system could also be potentially exploited in other medical applications or in micromanipulation tasks under an optical microscope [117].

IV. CONCLUSION

In the recent past, the advent of low-power and low-cost miniaturized CMOS image sensors together with MEMS technologies has enabled the realization of swallowable wireless camera pills. Currently, WCE represents a milestone in the evolution of endoscopic procedures, since it allows reliable and efficient diagnosis of GI tract pathologies, i.e., Barret esophagus, obscure bleeding, iron-deficiency anemia and small and large bowel tumors.

WCE can be considered as a noteworthy example of disruptive technology, since it represents an appealing alternative to traditional diagnostic techniques, preventing discomfort or the need to sedate the patient, as well as the risks of conventional endoscopy. These advantages have the potential to encourage patients to undergo GI tract examinations and the benefit of detecting and treating diseases in asymptomatic and still treatable conditions. Currently available clinical products enable visual diagnosis and simple diagnostic functionalities only; instead, running technological advancements, e.g., high efficiency power sources and micro actuators, are able to guarantee the development of active locomotion devices, provided with complete and accurate diagnostic and tissue treatment therapeutic modules.

Finally, exploitation of WCE knowledge and rescaling and/or redesign processes of these endoscopic devices will allow the development of systems for approaching other districts of the human body, such as the vascular circuit.

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Gastone Ciuti (M’10) received the M.S. degree (with honors) in biomedical engineering from the University of Pisa, Italy, in 2008. He is currently working toward the Ph.D. degree in biorobotics at the BioRobotics Institute, Scuola Superiore Sant’Anna, Pisa.

His current research interests include robotic endoscopy and robotic surgery and design of platform and capsule robots for biomedical applications.

Arianna Menciassi (M’00) received the laurea degree in physics (with honors) from the University of Pisa, Pisa, Italy, in 1995. In the same year, she joined the Scuola Superiore Sant’Anna, Pisa, as a Ph.D. student in bioengineering and she received the Ph.D. degree in 1999.

Currently, she is a Professor of biomedical robotics at the Scuola Superiore Sant’Anna. Her main research interests include the fields of biomedical micro and nano-robotics, surgical robotics, mechatronics and microsystem technologies. She

has been working on international and European projects on the development of endoscopic capsules since the year 2000. She is still working on several projects for the development of robotic systems for therapeutic, diagnostic and surgical applications. She is author of about 100 ISI papers and coinventor of about ten international patents.

Paolo Dario (M’81-F’05) received the Dr.Eng. degree in mechanical engineering from the University of Pisa, Pisa, Italy, in 1977.

He is currently a Professor of biomedical robotics at the Scuola Superiore Sant’Anna, Pisa. He has been a Visiting Professor at Brown University, Providence, RI, U.S., at the Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland, at Waseda University, Tokyo, Japan, at the College de France, Paris, at the Ecole Normale Supérieure de Cachan, France, and at Zhejiang University, China. He is the Director of the BioRobotics Institute of Scuola Superiore Sant’Anna, where he supervises a team of about 120 researchers and Ph.D. students, and the Director of Polo Sant’Anna Valdera, a Research Center located in Pontedera (PI). His main research interests are in the fields of medical robotics, bio-robotics, mechatronics and micro/nanoengineering, and specifically in sensors and actuators for the above applications, and in robotics for rehabilitation. He is the coordinator of many national and European projects, the editor of two books on robotics, and the author of more than 250 scientific papers (more than 150 on ISI journals). He is Editor-in-Chief, Associate Editor and member of the Editorial Board of many international journals. He has been a plenary invited speaker in many international conferences. He has served as President of the IEEE Robotics and Automation Society in the years 2002 and 2003. He has been the General Chair of the BioRob’06 Conference (First IEEE/RAS-EMBS International Conference on Biomedical Robotics and Biomechatronics), of ICRA 2007 (International Conference on Robotics and Automation), ISG 2008 (6th Conference of the International Society for Gerontechnology) and of the First National Congress of Bioengineering (GNB 2008).

Prof. Dario is a Fellow of the European Society on Medical and Biological Engineering and a recipient of many honors and awards, such as the Joseph Engelberger Award. He is also a member of the Board of the International Foundation of Robotics Research (IFRR). In 2009, he was appointed Fellow of the School of Engineering of the University of Tokyo.