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Reliability and Biostability of Microfabricated Implantable Medical Devices: Towards Standardized Manufacturing and Lab-Bench/Preclinical Testing

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A special issue of Micromachines (ISSN 2072-666X). This special issue belongs to the section "E：Engineering and Technology".

Deadline for manuscript submissions: closed (25 February 2022) | Viewed by 17374

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Special Issue Editors

Dr. Maria Vomero

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Guest Editor

Department of Electrical Engineering and Biomedical Engineering, Columbia University, New York, NY 10027, USA
Interests: microtechnologies; bioelectronics; neural interfaces; carbon electrodes; biostability and reliability of medical devices

Dr. Giuseppe Schiavone

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Guest Editor

Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, Ecole Polytechnique Fédérale de Lausanne, 1202 Geneva, Switzerland
Interests: microtechnology; neural interfaces; soft bioelectronics; translational research; biomimetic in vitro models

Special Issue Information

Dear Colleagues,

We are pleased to announce that our Special Issue for MDPI Micromachines, focused on preclinical testing of microfabricated implantable devices, is now open for submissions.

Micro- and nano-technologies applied to biomedical research have increasingly gained popularity in the fields of bioelectronics and medical device manufacturing due to their design versatility, low-cost and high-throughput manufacturing, and high structural biocompatibility. Microfabrication processes are prime tools for the realization of implantable micro- and nano-devices with a wide variety of embodiments, ranging from polymer-based implants to highly integrated silicon-based systems. There is still, however, a gap between the manufacturing phase and the deployment of such devices into clinical scenarios. One limiting factor is the current lack of standardized lab-bench tests for assessing and predicting the reliability and biostability of microfabricated biomedical implants.

This Special Issue will report advances in the development of biomedical engineering techniques, platforms, and testing protocols for evaluating the reliability and biostability of microfabricated implantable medical devices. The scope includes, but is not restricted to, micro and nano- implantable technologies, bioelectronics, neural interfaces, implantable sensors, and actuators, as well as associated challenges in materials, modeling, and metrology that will enable assessing and predicting their reliability and biostability.

In particular, this Special Issue will welcome manuscripts that cover topics including, but not limited to, the following:

Microfabrication technologies, process chains, in-line tests, and related reliability monitoring and inspection methods;
Electrode technologies and techniques to enhance electrodes performance and reliability;
Electrical, electrochemical, and electromechanical test platforms and protocols;
Connectorization and packaging, with the associated characterization techniques;
Sterilization procedures and associated characterization techniques;
Implantation-aids (tools) and techniques in preparation for successful surgeries;
Performance, stability, and reliability testing of micro- and nano- implantable devices in pseudo in vivo platforms, and ex vivo and in vivo models for preclinical validation.

We look forward to receiving your submissions!

Dr. Maria Vomero
Dr. Giuseppe Schiavone
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Micromachines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

bioelectronics
implantable medical devices
micro- and nano-fabrication technologies
biostability testing
reliability testing
in vitro platforms
preclinical validation

Published Papers (6 papers)

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Research

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14 pages, 3014 KiB

Open AccessArticle

Thin Film Encapsulation for LCP-Based Flexible Bioelectronic Implants: Comparison of Different Coating Materials Using Test Methodologies for Life-Time Estimation

by Anna Pak, Kambiz Nanbakhsh, Ole Hölck, Riina Ritasalo, Maria Sousa, Matthias Van Gompel, Barbara Pahl, Joshua Wilson, Christine Kallmayer and Vasiliki Giagka

Micromachines 2022, 13(4), 544; https://0-doi-org.brum.beds.ac.uk/10.3390/mi13040544 - 30 Mar 2022

Cited by 6 | Viewed by 3799

Abstract

Liquid crystal polymer (LCP) has gained wide interest in the electronics industry largely due to its flexibility, stable insulation and dielectric properties and chip integration capabilities. Recently, LCP has also been investigated as a biocompatible substrate for the fabrication of multielectrode arrays. Realizing a fully implantable LCP-based bioelectronic device, however, still necessitates a low form factor packaging solution to protect the electronics in the body. In this work, we investigate two promising encapsulation coatings based on thin-film technology as the main packaging for LCP-based electronics. Specifically, a HfO₂–based nanolaminate ceramic (TFE1) deposited via atomic layer deposition (ALD), and a hybrid Parylene C-ALD multilayer stack (TFE2), both with a silicone finish, were investigated and compared to a reference LCP coating. T-peel, water-vapour transmission rate (WVTR) and long-term electrochemical impedance spectrometry (EIS) tests were performed to evaluate adhesion, barrier properties and overall encapsulation performance of the coatings. Both TFE materials showed stable impedance characteristics while submerged in 60 °C saline, with TFE1-silicone lasting more than 16 months under a continuous 14V DC bias (experiment is ongoing). The results presented in this work show that WVTR is not the main factor in determining lifetime, but the adhesion of the coating to the substrate materials plays a key role in maintaining a stable interface and thus longer lifetimes. Full article

(This article belongs to the Special Issue Reliability and Biostability of Microfabricated Implantable Medical Devices: Towards Standardized Manufacturing and Lab-Bench/Preclinical Testing)

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17 pages, 1774 KiB

Open AccessArticle

Comparison of the In Vitro and In Vivo Electrochemical Performance of Bionic Electrodes

by Alexander R. Harris, Carrie Newbold, Dimitra Stathopoulos, Paul Carter, Robert Cowan and Gordon G. Wallace

Micromachines 2022, 13(1), 103; https://0-doi-org.brum.beds.ac.uk/10.3390/mi13010103 - 09 Jan 2022

Cited by 12 | Viewed by 1969

Abstract

The electrochemical performance of platinum electrodes was assessed in vitro and in vivo to determine the impact of electrode implantation and the relevance of in vitro testing in predicting in vivo behaviour. A significant change in electrochemical response was seen after electrode polarisation. As a result, initial in vitro measurements were poor predictors of subsequent measurements performed in vitro or in vivo. Charge storage capacity and charge density measurements from initial voltammetric measurements were not correlated with subsequent measurements. Electrode implantation also affected the electrochemical impedance. The typically reported impedance at 1 kHz was a very poor predictor of electrode performance. Lower frequencies were significantly more dependent on electrode properties, while higher frequencies were dependent on solution properties. Stronger correlations in impedance at low frequencies were seen between in vitro and in vivo measurements after electrode activation had occurred. Implanting the electrode increased the resistance of the electrochemical circuit, with bone having a higher resistivity than soft tissue. In contrast, protein fouling and fibrous tissue formation had a minimal impact on electrochemical response. In vivo electrochemical measurements also typically use a quasi-reference electrode, may operate in a 2-electrode system, and suffer from uncompensated resistance. The impact of these experimental conditions on electrochemical performance and the relevance of in vitro electrode assessment is discussed. Recommended in vitro testing protocols for assessing bionic electrodes are presented. Full article

(This article belongs to the Special Issue Reliability and Biostability of Microfabricated Implantable Medical Devices: Towards Standardized Manufacturing and Lab-Bench/Preclinical Testing)

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11 pages, 368 KiB

Open AccessArticle

Single-Pass VDD Pacing Lead for Cardiac Resynchronization Therapy: A Reliable Alternative

by Silvius-Alexandru Pescariu, Raluca Şoşdean, Bogdan Enache, Răzvan I. Macarie, Mariana Tudoran, Cristina Tudoran, Cristian Mornoş, Adina Ionac and Sorin Pescariu

Micromachines 2021, 12(8), 978; https://0-doi-org.brum.beds.ac.uk/10.3390/mi12080978 - 18 Aug 2021

Cited by 1 | Viewed by 1870

Abstract

(1) Background: Cardiac resynchronization therapy (CRT) systems can be simplified by excluding the atrial lead and using a Ventricular-Dual-Dual (VDD) pacing lead. Possible disadvantages might include atrial undersensing and Ventricular-Ventricular-Inhibition (VVI) pacing. Because literature data concerning these systems are scarce, we analyzed their benefits and technical safety. (2) Methods: this retrospective study compared 50 patients implanted with VDD–CRT systems (group A), mainly because of unfavorable venous anatomy concerning the complication rate, with 103 subjects with Dual-Dual-Dual (DDD)–CRT systems (group B) implanted during 2000–2016 and 49 (group C) during 2016–2020. To analyze the functional parameters of the devices, we selected subgroups of 27 patients (subgroup A) and 47 (subgroup B) patients with VDD–CRT in 2000–2016, and 36 subjects (subgroup C) with DDD–CRT implanted were selected in 2017–2020. (3) Results: There was a trend of a lower complication rate with VDD–CRT systems, especially concerning infections during 2000–2016 (p = 0.0048), but similar results were obtained after rigorous selection of patients and employment of an upgraded design of devices/leads. With a proper device programing, CRT pacing had similar results, atrial undersensing being minimal (p = 0.65). For VDD-systems, VVI pacing was recorded only 1.7 ± 2.24% of the time. (4) Conclusions: In patients with a less favorable venous anatomy, VDD–CRT systems may represent a safe alternative regarding complications rates and functional parameters. Full article

(This article belongs to the Special Issue Reliability and Biostability of Microfabricated Implantable Medical Devices: Towards Standardized Manufacturing and Lab-Bench/Preclinical Testing)

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15 pages, 1649 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

Post-Operative Monitoring of Intestinal Tissue Oxygenation Using an Implantable Microfabricated Oxygen Sensor

by Jamie R. K. Marland, Mark E. Gray, David J. Argyle, Ian Underwood, Alan F. Murray and Mark A. Potter

Micromachines 2021, 12(7), 810; https://0-doi-org.brum.beds.ac.uk/10.3390/mi12070810 - 10 Jul 2021

Cited by 6 | Viewed by 3573

Abstract

Anastomotic leakage (AL) is a common and dangerous post-operative complication following intestinal resection, causing substantial morbidity and mortality. Ischaemia in the tissue surrounding the anastomosis is a major risk-factor for AL development. Continuous tissue oxygenation monitoring during the post-operative recovery period would provide early and accurate early identification of AL risk. We describe the construction and testing of a miniature implantable electrochemical oxygen sensor that addresses this need. It consisted of an array of platinum microelectrodes, microfabricated on a silicon substrate, with a poly(2-hydroxyethyl methacrylate) hydrogel membrane to protect the sensor surface. The sensor was encapsulated in a biocompatible package with a wired connection to external instrumentation. It gave a sensitive and highly linear response to variations in oxygen partial pressure in vitro, although over time its sensitivity was partially decreased by protein biofouling. Using a pre-clinical in vivo pig model, acute intestinal ischaemia was robustly and accurately detected by the sensor. Graded changes in tissue oxygenation were also measurable, with relative differences detected more accurately than absolute differences. Finally, we demonstrated its suitability for continuous monitoring of tissue oxygenation at a colorectal anastomosis over a period of at least 45 h. This study provides evidence to support the development and use of implantable electrochemical oxygen sensors for post-operative monitoring of anastomosis oxygenation. Full article

(This article belongs to the Special Issue Reliability and Biostability of Microfabricated Implantable Medical Devices: Towards Standardized Manufacturing and Lab-Bench/Preclinical Testing)

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9 pages, 1659 KiB

Open AccessArticle

Reliability of Neural Implants—Effective Method for Cleaning and Surface Preparation of Ceramics

by Patrick Kiele, Jan Hergesell, Melanie Bühler, Tim Boretius, Gregg Suaning and Thomas Stieglitz

Micromachines 2021, 12(2), 209; https://0-doi-org.brum.beds.ac.uk/10.3390/mi12020209 - 19 Feb 2021

Cited by 6 | Viewed by 2394

Abstract

Neural implants provide effective treatment and diagnosis options for diseases where pharmaceutical therapies are missing or ineffective. These active implantable medical devices (AIMDs) are designed to remain implanted and functional over decades. A key factor for achieving reliability and longevity are cleaning procedures used during manufacturing to prevent failures associated with contaminations. The Implantable Devices Group (IDG) at University College London (UCL) pioneered an approach which involved a cocktail of reagents described as “Leslie’s soup”. This process proved to be successful but no extensive evaluation of this method and the cocktail’s ingredients have been reported so far. Our study addressed this gap by a comprehensive analysis of the efficacy of this cleaning method. Surface analysis techniques complemented adhesion strengths methods to identify residues of contaminants like welding flux, solder residues or grease during typical assembly processes. Quantitative data prove the suitability of “Leslie’s soup” for cleaning of ceramic components during active implant assembly when residual ionic contaminations were removed by further treatment with isopropanol and deionised water. Solder and flux contaminations were removed without further mechanical cleaning. The adhesive strength of screen-printed metalisation layers increased from 12.50 ± 3.83 MPa without initial cleaning to 21.71 ± 1.85 MPa. We conclude that cleaning procedures during manufacturing of AIMDs, especially the understanding of applicability and limitations, is of central importance for their reliable and longevity. Full article

(This article belongs to the Special Issue Reliability and Biostability of Microfabricated Implantable Medical Devices: Towards Standardized Manufacturing and Lab-Bench/Preclinical Testing)

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Other

Jump to: Research

11 pages, 890 KiB

Open AccessOpinion

Biomedical Microtechnologies Beyond Scholarly Impact

by Maria Vomero and Giuseppe Schiavone

Micromachines 2021, 12(12), 1471; https://0-doi-org.brum.beds.ac.uk/10.3390/mi12121471 - 29 Nov 2021

Cited by 5 | Viewed by 1966

Abstract

The recent tremendous advances in medical technology at the level of academic research have set high expectations for the clinical outcomes they promise to deliver. To the demise of patient hopes, however, the more disruptive and invasive a new technology is, the bigger the gap is separating the conceptualization of a medical device and its adoption into healthcare systems. When technology breakthroughs are reported in the biomedical scientific literature, news focus typically lies on medical implications rather than engineering progress, as the former are of higher appeal to a general readership. While successful therapy and diagnostics are indeed the ultimate goals, it is of equal importance to expose the engineering thinking needed to achieve such results and, critically, identify the challenges that still lie ahead. Here, we would like to provoke thoughts on the following questions, with particular focus on microfabricated medical devices: should research advancing the maturity and reliability of medical technology benefit from higher accessibility and visibility? How can the scientific community encourage and reward academic work on the overshadowed engineering aspects that will facilitate the evolution of laboratory samples into clinical devices? Full article

(This article belongs to the Special Issue Reliability and Biostability of Microfabricated Implantable Medical Devices: Towards Standardized Manufacturing and Lab-Bench/Preclinical Testing)

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