Acta Oto-Laryngologica. 2015; 135: 135–139

ORIGINAL ARTICLE

A new strategy for development of transducers for middle ear implants

RAFAEL URQUIZA1 & JAVIER LÓPEZ-GARCÍA2

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1

Department of Otolaryngology Laboratory of Experimental Otology, Research Institute, Ototech Research Group, University of Málaga and 2Department of Electronics and Ototech Research Group, University of Málaga, Málaga, Spain

Abstract Conclusion: The new strategy was efficient in designing and fabricating a new transducer for middle ear implants. The transducer could overcome important limitations (implantability of transducers, functional needs) of practical application of currently existing implants. The strategy uncovers the potential of translational research in this area of audiology. Objectives: To present an overview of research and development (R&D) strategic aspects and its practical implementation through one example of transducer development based on micro-electro-mechanical systems (MEMS) technology. Methods: (a) Rationale of technology in relation to the anatomical and functional features of the middle ear and implant requirements, (b) description and explanation of the different stages and decision-making process for the R&D of a MEMS transducer based on published pieces with their own experimental methods. Results: This R&D strategy focuses on achieving minute-size transducers by using MEMS technology. The process allows a designing-simulation-testing circle to be accomplished on the bench by special software, before fabrication and in vivo testing. The strategy, consequently, saves animal experiments, empowers the design capabilities and allows the fabrication of customized transducers for special problems. The developed prototypes are in the range of millimetres, fit the requirements of new implants and can be fabricated on a large scale and at low cost.

Keywords: MEMS, hearing loss, translational research

Introduction Hearing problems involve 70 million people among the population in Europe [1,2]. In Spain, for example, the estimated figure could be around 2 million MEIs. However, no more than one out of two conventional treatments may succeed and currently only a small number of people have been treated with middle ear implants (MEIs) around the world (very few hundreds according to published series) [3–6]. Therefore, many patients are still untreated or could not get suitable results. Although the ‘potential’ indications for an MEI extend to most of these problems, the actual figures for implanted patients are only a negligible percentage. What is the reason for this paradoxical situation? If emerging technologies are considered, it seems clear that the reasons underlying this situation derive from the present technology of

MEIs and, consequently, a technology-based approach to its solution would be auspicious. Our intention in this paper is to analyse the causes of the present situation and to present a new research and development (R&D) strategy to overcome several existing obstacles. Micro-electro-mechanical systems (MEMS) technology is increasingly applied to biomedical problems. It provides a wide range of solutions by producing integrated small mechanical systems that include not only electro-mechanical transducers of different types but electronic circuits. This represents a high potential for designing and development [7,8]. The ear is a mechanoelectric bio-transducer that converts sound into nerve impulses to be processed by the auditory system. The middle ear contains its main mechanical element: the tympanic-ossicular system (TOS). The TOS is a small millimetric and

Correspondence: Prof. Dr Rafael Urquiza, MD PhD, Instituto Universitario de Investigación, Laboratories of Experimental Otology, c/Severo Ochoa 4, Parque Tecnológico de Andalucía, University of Málaga, Campanillas, Malaga 29590, Spain. Tel: +34 952131617/+34 629718150. Fax: +34 952131630. E-mail: [email protected]

(Received 31 July 2014; accepted 12 September 2014) ISSN 0001-6489 print/ISSN 1651-2251 online Ó 2015 Informa Healthcare DOI: 10.3109/00016489.2014.969381

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delicate biological system that conducts precisely low energy vibrations towards the labyrinthine fluids within limited frequency and intensity ranges to keep the delicate sensory areas of the organ of Corti safe. Besides, the protection/accommodation effects include active mechanisms such as middle ear reflexes (stapedial and mallear) and feedback regulation dwelling on the cochlea and the central nervous system (CNS – efferent system). These key features, dimensions, precise performances and active regulation, could be emulated, at least in part, by MEMS technology. MEIs aim to imitate and empower the middle ear function. The processor and other components can be implanted near to the middle ear but the transducers should necessarily be implanted totally or partially within the middle ear cavities. Nowadays, middle ear transducers are mainly fabricated with small machines technology leading to device dimensions in the range of 1.5–3 cm that often extend beyond the actual size of the anatomic cavities (Figure 1). This results in two adverse situations. First, some patients (potential candidates) could not house the transducer/s and consequently they are rejected for surgery. Second, provided that the candidate passes the selection process, the surgical intervention becomes highly complex and time-consuming, requiring a highly skilful surgeon (above the standard). In fact companies delivering new MEIs look carefully for those top surgeons to increase the success of their implants, which is not an easy task. Consequently, the size of the

10 mm

2 cm

FN

M MEMS EAC

OW

SMT

TM

V RW

SMT

MC

EAC

transducers is a key feature for the clinical applicability of MEIs and should be considered strategic for R&D in this field [9]. Therefore, new transducers with smaller size than the existing ones could be of substantial benefit. On the other hand, the high cost of the devices, which is substantially affected by the fabrication technique (small machines), is also a restricting factor, both resulting in a limited application of MEIs around the world. However, this status quo could be overcome if we consider the potential of MEMS with respect to other existing mechanical technologies for transducer development and fabrication, that is derived from adequacy of the dimensions to implantation cavities, cost, surgical procedure, biotolerance, etc. (Figure 2). MEMS technology can produce custom transducers in the range of millimetres, which is a crucial advantage. The different available transduction systems (sensing: piezoresistivity, piezoelectricity, capacitive, optical, resonance; acting: piezoelectric, electromagnetic, electrostatic, thermal) and particularly the wider design potential can fit conveniently in new implant transducers, according to biological or technical requirements [7]. Another interesting characteristic of MEMS derives from the potential of their own development process, because: (a) MEMS can be designed directly on the bench according to functional and anatomical requirements; (b) they can be tested in numerical models (avoiding costly and unwanted animal experiments); (c) different prototypes can be fabricated simultaneously making the process cost-effective and experimentally very powerful; and (d) the final product could be obtained on a large scale and at low cost. All these become clear advantages over the small machines technique currently used. The derived benefits could be significant: (a) low size of transducers leading to easier and safer implantability, (b) low cost leading to larger availability of devices, especially in unfavourable economic situations, (c) easier fabrication of a wide range of transducer designs leading to ‘custom prostheses’ and, resulting from the previous benefits, (d) a wider range of problems/patients can actually be treated.

TC

Sensory cells

Ear dimensions

Figure 1. Aspect of a temporal bone showing a mastoidectomy cavity (MC) and other structures that should accommodate the transducers during middle ear implant surgery and the relative dimensions of a current small machine transducer (SMT). Upper right corner: functionally important intratympanic elements as represented in a coronal section of tympanic cavity and their relative dimensions to an SMT and MEMS transducer (MEMS). EAC, external auditory canal; FN, facial nerve; M, malleus ossicle; OW, oval window niche; RW, round window niche; TC, tympanic cavity; TM, tympanic membrane; V, vestibule.

Technology Size range Cost per unit

Inner ear mechanics

Nanomachines nm

Tympanic ossicles

MEMS

um +

Mastoid cavities

Small machines mm

++

cm ++++

Figure 2. Existing mechanical technologies pertinent to the development of middle ear transducers, their size range, their relationships to the dimensions of different ear structures and to the cost of transducers.

Strategy for middle ear transducers R&D

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Nevertheless, provided that the ‘size’ of the transducer is crucial, the application of MEMS implies not only advantages but also certain limitations. In general, smaller transducer size implies better implantability, but MEMS deliver lower energy than small machines. Accordingly, the delivered energy must adequate for the stimulation point and, consequently, the decision about that point along the mechanical pathway of the ear is central to the design process. In general, the closer the stimulation point is to the organ of Corti, the lower the energy required and, subsequently, the smaller the transducer size that can be used.

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Selection of stimulation point

Energy & anatomical information (associated to simulation point)

Design (Transduction, material, housing, geometric design)

Bench lab tests (Math models)

Material and methods Apart from the description of the rationale of the R&D strategy and process, the corresponding experimental methods were detailed earlier [10–15]. Results MEMS middle ear transducers: one example of design and fabrication We have considered these facts to develop new transducers entailing dimensions in the millimetres range but their practical application required a particular R&D strategy (Figure 3). Before development of the transducer itself, it was necessary: (a) to adapt other previously developed elements (processor, algorithms, fitting platform, PC interface, software, etc.) [10] and (b) to obtain precise information in selected patients about the energy required for the stimulation of the selected point along the mechanical pathway. Since we preferred a small transducer and a lower energy range for the above-mentioned reasons, we selected a stimulation point closer to the sensory epithelium: labyrinthine fluids at the stapes-footplate level. Then, a series of experiments were carried out (Figure 4) with the help of existing transducers connected to the fitting platform (developed earlier) and a specially developed and constructed hydrodynamic model of labyrinthine spaces [11] to obtain precise information about actual energy requirements. This information allowed us to design the new transducer, including selection of the transduction type (piezoelectric in this case), geometrical characteristics (according to the anatomical area, housing system, biotolerance, safety, etc.) and other target functions. Thereafter, designing, testing and refining of prototypes (dimensions, geometrical designs, arrangement, etc.) could be carried out entirely in the laboratory with the help of different software including CoventorWareÒ and ANSYSÒ. This stage is strategically

Fabrication (Processes & procedure design)

Prototypes laboratory tests (Mechanical performances)

Tests in animals (Safety, biotolerance, effectiveness, etc.)

Human clinical trials (Safety, biotolerance, effectiveness, etc.)

Figure 3. Strategically significant stages for the research and development process of a MEMS transducer destined for a middle ear implant.

significant because the performances of different prototypes can be predicted, saving time, costly fabrication process and animal experiments. Once the different transducer prototypes were designed, lab-tested and refined, the convenient models were fabricated in a White chamber [12–14]. The main processes used in this case were thin-film deposition and patterning, wet etching, deep reactive ion etching (DRIE), bulk micromachining and silicon-on-insulation. The combination of these techniques required the development of a compatible process to meet temperature budgets and chemical and physical constraints. The fabricated prototypes (Figure 5) were then tested as regards their actual mechanical performances, in particular their displacement ability, by using precise techniques such as atomic force microscopy (Figure 6) in the laboratory [15]. The transducer must be surgically positioned within a biocompatible housing system that anchors the transducer to the otic capsule (oval niche in this case),

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R. Urquiza & J. López-García Experimental design Processor

1

Patient

Prototype A

Prove effective fitting

Conventional output Transducer

2

Processor

Labyrinth hydrodynamic model

Prototype A

Artificial perilymph

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MEMS Actuator

3

Labyrinth hydrodynamic model

Processor

Artificial perilymph

Prototype B Figure 4. Set of experiments used to obtain information about stimulation energy in actual patients for designing the MEMS transducer and to test the fitting platform.

0.9

MEMS

Fa

R.

cia

ln

1.70 1.65

1 mm

0.5

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er

ve

Positioning (surgical view)

Housing S. Figure 5. The fabricated MEMS transducer (Ototech Patent ES 2352921 A1) close to the stapes and the incus long process showing their relative dimensions, and the housing system containing the MEMS transducer, as it should be implanted in the stimulation site (oval window niche). R.W., round window.

Peak displacement 51–56 nm

11.9

Z: 1

allowing actuation on the labyrinthine fluids and facilitating biotolerance of the complete transduction component (MEMS + housing). Further, its mechanical performances can be also tested ‘in vivo’ by laser Doppler vibrometry.

nm

Peak range deformation (20 v applied) 110–112 nm Base range deformation (no voltage applied) 54–60 nm

X:

7.0

µm

Figure 6. Results of the acting displacement obtained by the atomic force microscopy technique (from R. Urquiza et al. [15], with permission).

Discussion Current R&D strategies for new medical devices are increasingly oriented to different objectives: (a) to obtain a device that effectively fulfils its functional objectives; (b) to obtain a product applicable to a wide patient population at the lowest possible cost; (c) to

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Strategy for middle ear transducers R&D reduce animal and human experiments, and (d) to accelerate the translational process of the product to industry by facilitating fabrication, commercialization, clinical trials, etc. At present, clinical application of MEIs is far from exploiting their full potential. Problems of implantability, actual indications, cost and others still exist, and they are mostly derived from existing transducers. Consequently, a change is needed to surpass the situation, and new R&D strategies for transducers with their experimental designs are necessary. The implementation of new technologies and strategies in both the design and fabrication processes, such as MEMS, numerical modelling, integration of computer design, testing and fabrication, is changing the R&D scenario. However, their implementation implies education, organization and working in a transdisciplinary environment. In this new scenario, the creation of new translational research groups with a special ‘philosophy’, structure and education is a must that requires a particular effort, but it pays off. In this case, the new MEMS-based strategy overcomes existing obstacles and the new transducer opens the possibility to develop a new mechanical implant that could be economically convenient, easily implantable in the middle ear and widely applicable. It could be used to restore hearing in different hypoacusis types (conductive, sensorineural and mixed) and pathological conditions, even in radically operated middle ear cavities (functionalization). Although the initial R&D of the currently available transducers used piezoelectric and/or different types of electromagnetic transduction, other available MEMS transduction techniques are still unexplored or under preliminary evaluation. Conclusions The new strategy based on MEMS technology allows us to design and fabricate conveniently new customized small transducers, and MEIs will benefit from them in terms of implantability, cost and expanded applications. The presented example of design and fabrication demonstrates that both MEMS and the middle ear are excellent partners for translational auditory research and we recommend this technology for similar purposes. Its implementation implies the creation of a transdisciplinary environment, but it pays off.

Acknowledgment This work was supported by the Fondo de Investigación Sanitaria, Ministerio de Sanidad y Consumo (Spain) through the project PI052193.

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Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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A new strategy for development of transducers for middle ear implants.

The new strategy was efficient in designing and fabricating a new transducer for middle ear implants. The transducer could overcome important limitati...
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