Microtechnology in Surgical Devices 11

Chapter

Marc O. Schurr

11.1 Introduction • Extracorporeal devices such as telemetric health monitoring systems (e.g., wearable electrocardio- Microtechnology plays an important role in the devel- gram [ECG] monitors) opment of medical and surgical devices. Since the early • Intracorporeal devices such as intelligent surgical 1990s [13], there has been growing interest in using instruments (e.g., tactile laparoscopic instruments) microtechnology for miniaturization of medical de- • Implantable devices such as telemetric implants vices or for increasing their functionality through the (e.g., cardiac pacemakers) integration of smart components and sensors. • Endoscopic diagnostic and interventional systems Microsystems technology (MST), as it is called in such as telemetric capsule endoscopes Europe, or microelectromechanical systems (MEMS), as it is called in the United States, combine electronic Recently there has been an increase in medical MST- with mechanical components at a very high level of sys- related research and development (R&D) activities, tems integration. Microsystems are smart devices that both on the side of research institutes and indus- integrate sensors, actuators, and intelligent electronics try. While routine clinical applications of MST-en- for on-board signal processing [27]. In the industrial hanced surgical devices are still limited to a number area these technologies are used to make various kinds of larger volume applications such as pacemakers of sensor elements, such as accelerometers for airbags [28] (Fig. 11.1), a number of developments are in in cars, microfluidic components, such as inkjet print later-stage experimental research or in clinical studies. heads, and other elements. In the medical field, MST Medical applications of MST technologies are grow- is used in a number of products such as pacemakers ing at double-digit compounded growth rates [17], or hearing implants [5]. While most MST components which led to a forecasted global market volume of over are produced using semiconductor processes [27], $ 1 billion in 2006. there are a number of alternative technologies enabling the production of a broad variety of microdevices and components in virtually all industry sectors. The potential of MST for medical use was recognized more 11.2 MST in Medical Devices: than a decade ago [13, 14], and has since then led to Challenges and Opportunities the development of numerous practical applications [21]. The community developing and using MST for medi- Sometimes MST and nanotechnology are terms that cal devices is a very heterogeneous scene of academic are used synonymously since both concern miniatur- researchers, specialized MST companies, medical de- ized devices. However, both technologies are entirely vice corporations, start-ups, and clinicians. In order to different. While MST deals with components in the better understand the challenges and opportunities of submillimeter size, nanotechnology concerns submi- MST in medical devices, our institute has a conducted crometer structures. Nanotechnology mainly refers to global survey among executives from research and innovating material properties such as nanostructured industry on the use of medical microsystems technol- surfaces with special biocompatibility features and may ogy. This survey was done in 2004 within the scope of be an important enabler for future biomedical prod- the netMED project funded by the European Union ucts in the future, also combined with MST devices. (GIRT-CT-2002-05113). The study was based on a Based on the high density of functional integration standardized questionnaire and included 110 persons, and the small space requirements, MST components with about 50% of participants coming from the medi- are enhancing surgical devices in different areas, and cal device industry and the remaining participants can be subdivided into the following applications: from R&D institutes and MST companies. 90 IV Surgical Instrument in Novations

a b

Fig. 11.1 Telemetric pacemaker for remote patient monitoring. Source: Biotronik GmbH, Berlin, Germany. a Pacemaker with telemetry units. b Mobile data transfer unit, like a cellular phone

Asked about the advantages expected in the next 5 high-tech reimbursement. This applies especially to years from the applications of MST in medical devices, the European market place. the study participants named new product opportuni- As for the types of microsystems components judged ties for existing market segments and for entering new most important for medical products in the future, our market segments along with product miniaturization study participants named various types of sensors such potential as their key expectation. The most important as biosensors, chemical sensors, pressure sensors, and barriers to innovation in medical MST are high initial microfluidic structures. This indicates that experts see investment load, general skepticism of users (doctors, the future of MST in medical devices mainly in the im- patients), and unclear reimbursement conditions for provement of device intelligence through sensors and MST-enhanced medical devices or MST-related diag- in using microactuators for miniaturization interven- nostic or therapeutic procedures. This mainly refers tion instruments (Fig. 11.2). to telemetric technologies such as remote ECG diag- Of particular importance will be the definition of nostics and remote cardiac pacemaker or implantable standards [15] and common interfaces to facilitate the defibrillator monitoring. use of MST components, especially in markets with Asked about the preconditions necessary to im- smaller product volumes, such as medicine, if com- prove the application of MST in medical devices, sur- pared with large-scale industrial applications, such as vey participants named the availability of standardized automotive, environmental of aerospace. MST elements, comparable to standardized electronic elements, customizable integrated systems to facilitate the use of MST components in medical devices, and the increase of acceptance of these technologies among 11.3 Areas of MST Applications in Medical payers in the health care system. Devices This shows that barriers to innovation in the field of medical MST are not only on the side of the tech- As mentioned above, the application of MST compo- nology with its particular challenges, but also on the nents in medical devices can mainly be grouped into market side in terms of unsolved issues in medical four different areas. This classification refers to current Marc O. Schurr Chapter 11 Microtechnology in Surgical Devices 91

Fig. 11.2 netMED global survey on medical microsystems technology: types of microsystems components seen most important for medical products in the future. a Sensors. b Actuators. c Other 92 IV Surgical Instrument in Novations

focal applications of MST in the medical field and is standard technology. A good example of this class of neither systematic nor complete. MST applications is sensor-enhanced surgical instruments. The concept of restoring tactile feedback in laparoscopic surgery has been around for more than a decade. Several attempts have been made to integrate 11.3.1 Extracorporeal MST-Enhanced Devices tactile sensors into the jaws of laparoscopic instruments to allow palpation and mechanical characterization The area of extracorporeal MST-enhanced devices is of tissues during surgery, such as the surgeon would probably the most mature and established field of MST do with his or her hand in open surgery [22]. In the applications. There are numerous examples of MST past, some attempts to create tactile sensors have failed, components integrated into external diagnostic and partly related to complex technologies that could not monitoring systems. These include handheld diagnos- be efficiently applied in this small market segment. tic devices such as optical bilirubin analyzers based Since tactile sensing in laparoscopic surgery is still on a MST spectrometer [29], sensors embedded into an attractive proposition from a medical standpoint, smart textiles or wearable ECG foils [2] (Fig. 11.3). new attempts are being made to realize such instru- Often MST applications are combined with wire- ments on a more cost-friendly technology basis. less technologies to enable patient monitoring without One of these is a program carried out by our own restrictions in mobility. Miniaturized telemetry units institution to develop a polymer sensor array, which using the Bluetooth standard transmit parameters to is elastic, compliant and can be attached to the tip of a patient data management systems and electronic a laparoscopic instrument as a disposable. This sensor patient records. This allows both the patient and the (Fig. 11.4) is composed of a conductive and a resistive attending physician to deal efficiently with monitoring layer of polymer separated by a perforated layer. data. Through exerting external pressure, the resistive coupling between the elastic conductive membranes is changed, indicating the force across the sensor array. The current forceps prototype (Fig. 11.5) has an array 11.3.2 Intracorporeal MST-Enhanced Devices with 32 sensory elements. The force exerted on each element is visualized on a display. Experimental evalu- Intracorporeal but not implantable medical and surgi- ation of the tactile forceps has shown that objects of cal devices use MST components to provide additional different size and hardness can be well different shaded qualities and functions that cannot be realized with from their neighboring structures.

Fig. 11.3 Telemetric three-channel ECG system. Source: Fraunhofer Institute Pho- tonic Microsystems, Dresden, Germany Marc O. Schurr Chapter 11 Microtechnology in Surgical Devices 93

The resulting fluorescence can be enhanced by- lo cal tissue staining techniques. Figure 11.8 compares histological images obtained by this fluorescence laser scanning microscopy technique with conventional he- matoxylin and eosin (HE)-stained histology.

11.3.3 Implantable MST Devices

Telemetric implants are among the most important ap- Fig. 11.4 A polymer microsensor for tactile laparoscopic in- plications of MST in medicine. MST components im- struments (schematic drawing) planted into the human body include sensors of various types that measure specific health parameters, such as blood glucose [18] or blood pressure or flow [1, 4, In animal experiments (Fig. 11.6) objects simulating 30]. The signals are then transferred via telemetric coils lymph nodes at the mesenteric root could be localized to readout device outside of the body. A good example and differentiated using the instrument. for existing products in this field is cardiac pacemakers Further research will be required to optimize the or defibrillators that are equipped with miniaturized sensitivity and the applicability of tactile sensor arrays telemetry units to send cardiac parameters and param- for laparoscopic surgery. eters or their electrical interaction with a heart outside Another example of intracorporeal MST applica- of the body [28] (Fig. 11.1). The data are received by tions is advanced optical diagnostic systems for micro- a readout device similar to a cellular GSM phone and scopic analysis of tissues in situ [7]. The concept ofcon - then sent from there to a remote cardiovascular service focal laser scanning microscopy is widely known in the center. histological examination of tissues samples. Using the This allows improvement of patient monitoring and miniaturization potential of MST, laser scanning mi- implant maintenance, without the need to see the pa- croscopes can be scaled down to a level that they can be tient regularly. These kinds of telemetrically enhanced used via an endoscope directly inside the human body, cardiovascular implants based on MST are available on e.g., for in situ analysis of lesions suspicious for cancer the market for clinical use; in addition to the product, [8]. Figure 11.7 shows a prototype two axes microscan- advanced cardiovascular monitoring services are pro- ner with two miniature mirrors etched from silicon, vided by the same manufacturer. compared with the size of a regular 10-mm laparoscope. Other applications of intracorporeal MST include The two electrostatically driven mirrors pivot and scan the use of telemetric sensors for diagnostic and disease the laser beam across the tissue surface at video speed. monitoring purposes. Examples include the measure-

Fig. 11.5 A prototype of a tactile surgical instrument with the polymer sensor and force display system 94 IV Surgical Instrument in Novations

Fig. 11.6 Palpating an object simulating a lymph node at the Fig. 11.8 Histological images obtained by fluorescence laser mesenteric root (animal experiment) scanning microscopy technique (a), with conventional HE- stained histology (b). This experimental program has been conducted by a group of several research institutes, supported by grants from BMBF, Germany, and the European Union

comprises several MST components such as a pressure sensor and miniaturized telemetry coils. The medical concept behind this device is to monitor blood pressure values and to better adjust antihypertensive medi- cation in order to reach normal blood pressure values in a higher number of patients. Today only in a minor- ity of patients normotensive blood pressure values are achieved due to a lack in adequate monitoring and patient management means. This example underlines the principle that implantable sensory MST devices are mainly targeting sec- ondary disease prevention by slowing down disease Fig. 11.7 Microscanner for confocal fluorescence microscopy. progression or avoiding complications through con- Source: Medea Project, supported by the European Union sequent and consistent monitoring. Thus, MST-based monitoring systems will may a major impact on the prevention of disease progression to the benefit of both the patient and the healthcare system. ment of intravesical pressure in paraplegic persons Also on the therapeutic side, MST applications are to avoid overfilling of the bladder and the urinary important sources of innovation. Specific implants have tract [6]. been equipped with microsensors in order to monitor Our own group has been working with the company the function of the implant. Examples of this kind of Sensocor, Ltd., Karlsruhe, Germany, in the develop- application of MST in surgery include pressure sensors ment of an implantable telemetric blood pressure mea- integrated into endovascular stent grafts in order to surement sensor for the monitoring of hypertension detect residual blood flow through the aneurysm sac (Fig. 11.9). The implant is an integrated device that in endovascular treatment of abdominal aortic aneu- Marc O. Schurr Chapter 11 Microtechnology in Surgical Devices 95

Fig. 11.9 Concept of an implantable blood pressure measure- ment. Source: Sensocor, Ltd., Karlsruhe, Germany. The implant is an integrated device that comprises several MST components such as pressure sensors and miniaturized telemetry coils

rysm [3]. Another approach is to use microsensors in implants to detect concomitant disease, such as detection of glaucoma through pressure sensors integrated into an intraocular lens graft implanted for the treatment of cataract [26]. Also, the field of replacing lost organ function, and organ stimulation MST-based implants are of interest. This includes the restoration of lost or impaired sensory functions of the ear [5] and the eye [12, 20], or of Fig. 11.10 The E² self-propelling endoscope is a pneumati- traumatized nerves [23–25]. cally controlled inchworm that moves through the colon by a sequential adhering to the bowel wall and elongating/shortening the midsection. a Inchworm with imaging head and propelling body. b High flexibility 11.3.4 MST in Endoscopy

The field of endoscopy is an interesting area for the class of MST applications is the E² endoscope sys- application of MST, since high-functional integration tem of Era Endoscopy Srl, Pontedera, Italy, based and miniaturization, the two main characteristics of on research [16] conducted by the CRIM labora- MST, are an important advantage in this field. tory of Scuola Superiore Sant’Anna, Pisa (supported Besides microfiberoptics for the inspection of small- by a grant of IMC/KIST, Seoul, South Korea). The E² est tubular organs and body cavities, a big interest is in self-propelling endoscope (Fig. 11.10) is a pneumati- using MST for creating new locomotion technologies cally controlled inchworm that moves through the co- in the human body. A very good example is capsule lon by sequentially adhering to the bowel wall with its endoscopy [9] using a miniaturized optical camera proximal and its distal end and elongating/shortening system with telemetric image data transfer integrated the midsection. into an ingestible capsule. A number of MST elements The MST components used for this technology be- are used to realize the Pill-Cam capsule endoscope of sides the CMOS imaging and LED illumination include Given Imaging, Ltd., Yoqneam, Israel, such as CMOS microfluidic and -filter elements to support the pneu- image sensors, LED illumination diodes, imaging elec- matic locomotion mechanism. The clinical purpose be- tronics, and telemetric signal transfer components. hind self-propelling microendoscopes lies in the reduc- Farther down the road are self-locomoting endo- tion of the force exerted to the tissue, thus the reduction scopes that, unlike a capsule endoscope, can actively of pain during the procedure. The clinical benefit will propel through the digestive organs and be steered be improved patient acceptance of colonoscopy cancer into the desired direction. A good example for this screening programs in the future. 96 IV Surgical Instrument in Novations

11.4 Discussion Increasing standardization of MST components may help to solve this problem. Similar to electron- Microsystems technology is nowadays playing a major ics, where well-defined standardized components are role for improving products in the health care sector. available at low cost, standardized MST components In the last years, the development of MST applications such as pressure sensors, telemetry units, or optical has been boosted by the ability to manufacture MST structures not dedicated to a single application but for elements with high precision, reliability, and at accept- multiple purposes will become available. To achieve able costs. A considerable number of products used in this goal, it is important to formulate and respect tech- clinical routine today are functionally based on MST nical standards [15]. and allied technologies. But there are also a number of nontechnical prob- These applications include the medical high volume lems for MST that need to be overcome. Among the markets of cardiac rhythm management [28] or im- most important barriers to innovation seen by special- plantable hearing aids [5], as well as highly specialized ists from the field are unclear reimbursement condi- applications in the field of neural rehabilitation [23]. tions [10]. This shows that the further progress MST in Rebello [17] has identified a minimum of 25 major medicine not only depends on successful R&D and the research programs internationally, focusing only on establishment of technical standards, but also on the surgical MST and surgical sensors. This shows there availability of innovative reimbursement schemes that are major research efforts in progress that will deliver act as incentives for the use of advanced technology, further leads for device companies to develop advanced particularly in the areas of disease prevention and early medical products on the basis of MST. detection. Especially in these fields can innovation pro- The world market projection for MST and MST vide a significant leverage on reducing healthcare costs components in medical products was expected to in the mid and long term. This needs to be reflected exceed $1 billion by 2005 or 2006. This considerable in reimbursement for medical care enabled by MST or market potential will attract more industrial players to other advanced technologies. invest into microtechnology for medical and surgical products. 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