定量的、皮膚が創傷管理のためのコンフォーマルスキンのような電子システムの作製と評価
Summary
This article presents methods to fabricate and characterize a conformal, skin-like electronic system and protocols for the use in clinical applications, particularly on cutaneous wound management.
Abstract
Recent advances in the development of electronic technologies and biomedical devices offer opportunities for non-invasive, quantitative assessment of cutaneous wound healing on the skin. Existing methods, however, still rely on visual inspections through various microscopic tools and devices that normally include high-cost, sophisticated systems and require well trained personnel for operation and data analysis. Here, we describe methods and protocols to fabricate a conformal, skin-like electronics system that enables conformal lamination to the skin surface near the wound tissues, which provides recording of high fidelity electrical signals such as skin temperature and thermal conductivity. The methods of device fabrication provide details of step-by-step preparation of the microelectronic system that is completely enclosed with elastomeric silicone materials to offer electrical isolation. The experimental study presents multifunctional, biocompatible, waterproof, reusable, and flexible/stretchable characteristics of the device for clinical applications. Protocols of clinical testing provide an overview and sequential process of cleaning, testing setup, system operation, and data acquisition with the skin-like electronics, gently mounted on hypersensitive, cutaneous wound and contralateral tissues on patients.
Introduction
臨床研究および生物医学研究では、創傷治癒のモニタリングは、創傷1,2における組織形態学的変化の組織学的評価に基づいて侵襲的な方法に焦点を当てています。最近、電子技術の急速な進歩は、視覚的にデジタル画像3,4または共焦点走査顕微鏡と分光4,5を経由して、創傷治癒過程を調べることができ、高精度のイメージングと解析ツールの開発を可能にします。しかし、これらのイメージング手法は、高コスト、複雑な光学ツールや操作を必要とし、より重要なことには、患者は、試験中に固定化する必要があります。したがって、より正確な創傷管理を提供するために、簡単に使用できる、非侵襲的、定量的、安価、および多官能性であり、新しい装置およびシステムの必要性が存在します。
ここでは、温度や熱conduの正確な、リアルタイムのマッピングを提供し、皮膚のような電子システムを導入ctivityとは、非侵襲的デバイスのコンフォーマル積層を介した創傷部位での加熱の正確なレベルを提供します。このデバイスは、表皮6-9の技術、機械的および材料特性に適合するように設計されて皮膚に取り付けられた表皮電子システム（曲げ剛性、全体の厚さを、効果的な弾性率、および質量密度）のクラスを提供します。
デバイスは、患者10の臨床応用のために洗浄し、消毒することができ、生体適合性、肌に優しい、防水、および再利用可能な形で設計されています。創傷組織の近くに取り付けられたコンフォーマルな電子デバイスは水和に対応付け温度8と熱伝導率13の定量的記録を介して、創傷11,12に血流増加及び酵素反応によって引き起こされる炎症期（創傷治癒プロセスの1つ）、キャプチャ。実験と計算の研究はaccommodに最適なメカニックデザインを決定自然な動きを食べて、機械的な破壊せずに歪みを適用し、高忠実度信号の取得を提供しています皮膚の表面にコンフォーマルに積層皮膚のような電子機器の仕組みを延伸する基礎となる物理学を、キャプチャします。
この資料に記載されているプロトコルは、皮膚のような電子システム、機器の清掃、臨床現場での機器のセットアップ、および皮膚の傷の温度と熱伝導率の定量的なモニタリングのための臨床応用を含め、試験の準備のための微細加工の方法を提示します。
Protocol
Representative Results
Discussion
This article highlights the methods and protocols to fabricate a conformal, skin-like electronics system that enables conformal lamination near the wound tissues, which offers quantitative measurement of skin temperature and thermal conductivity mapping on the skin.
The key features include the utilization of novel techniques of materials transfer printing and hard-soft materials integration to design and develop the flexible/stretchable, soft electronic device. The use of biocompatible, elec…
Declarações
The authors have nothing to disclose.
Acknowledgements
この作品は、工学系研究科、バージニアコモンウェルス大学および電子デバイスのいくつかのライトバージニアマイクロエレクトロニクスセンターでの微細加工施設で調製したからスタートアップ資金によってサポートされていました。私たちは、掲載された記事10から取得した（本論文では図3と図5）、デバイスおよび臨床データのために貢献をした研究者を認めます。 W.-HYカスタムメイド、データ記録ソフトウェアに感謝義明服部。
Materials
| 3" Silicon wafer | University Wafer, USA | N/A | Use as carrier to fabricate the device |
| Acetone | Fisher Scientific, USA | A18-1 | Use to clean a wafer and to remove photoresist |
| Isopropanol (IPA) | Fisher Scientific, USA | A459-1 | Use to clean a wafer |
| AZ4620 photoresist | AZ Electrionic Materials, USA | N/A | Use to make patterns on metals and polymers |
| AZ400K developer | AZ Electrionic Materials, USA | N/A | Use to develop AZ4620 photoresist |
| Chromium etchant | Transene, USA | 1020AC | Use to etch Cr layer of device |
| Copper etchant | Transene, USA | ASP-100 | Use to etch Cu layer of device |
| Sylgard 184 Silicone Elastomer Kit (PDMS) | Dow Corning, USA | 39100000 | Use as a substrate for 'dry' retrieval |
| PI2545 polyimide | HD MicroSystem, USA | N/A | Use to encapsulate metal layer |
| Solaris | Smooth-On, USA | N/A | Use as substrate and to encapsulate device |
| Petridish | Carolina, USA | 741255 | Use as mold to make substrate |
| Water-Soluble Wave Solder Tape 5414 | 3M, USA | AM000000217 | Use to retrive device from PDMS layer |
| High Activity Liquid Stainless Steel Flux | Worthington, USA | 331929 | Use to remove oxidation layer on Cu |
| Flexible, micro-film cable | Elform, USA | N/A (customized) | Use to make the electrical connection between the electronic device and the data acquisition system |
| pH Neutral Cleaner | Australian Gold, USA | N/A | Use as disinfectant solution to clean device in clinical testing |
| Solder | Kester, USA | 24-6337-9703 | Use as material to solder hard wires |
| Ultraviolet lamp | Cole-Parmer, USA | 97600-00 | Use to activate PDMS layer as hydrophilic surface |
| Multiplexer | FixYourBoard, USA | U802 | Use to acquire measurements from six sensing components |
| DC/AC current source | Keithley, USA | 6221 | Use to supply current |
| SMD Digital Hot Air Rework Station | Aoyue, China | 968A+ | Use to solder hard wires, to electrically connect between the device and external instruments |
| Infrared camera | FLIR, USA | 435-0001-01-00 | Use to take infrared images in experiment |
| Digital multimeter | Fluke, USA | 117 | Use to check electrical connection |
| Lock-in amplifier | Stanford Research System, USA | SR830 | Use to perform four-point-probe-measurement |
| Electron beam evaporator | 9 scale Vacuum Products, USA | N/A (customized) | Use to deposit thin films (Cu and SiO2) |
Referências
- Dargaville, T. R., et al. Sensors and imaging for wound healing: A review. Biosens Bioelectron. 41, 30-42 (2013).
- Panuncialman, J., Hammerman, S., Carson, P., Falanga, V. Wound edge biopsy sites in chronic wounds heal rapidly and do not result in delayed wound healing. J Invest Dermatol. 129, S47-S47 (2009).
- Hess, C. T., Kirsner, R. S. . Orchestrating Wound Healing: Assessing and Preparing the Wound Bed. Adv Skin Wound Care. 16 (5), 246-257 (2003).
- Lange-Asschenfeldt, S., et al. Applicability of confocal laser scanning microscopy for evaluation and monitoring of cutaneous wound healing. J Biomed Opt. 17 (7), (2012).
- Crane, N. J., Elster, E. A. Vibrational spectroscopy: a tool being developed for the noninvasive monitoring of wound healing. J Biomed Opt. 17 (7), (2012).
- Jeong, J. W., et al. Materials and Optimized Designs for Human-Machine Interfaces Via Epidermal Electronics. Adv Mater. 25 (47), 6839-6846 (2013).
- Kim, D. H., et al. Epidermal Electronics. Science. 333 (6044), 838-843 (2011).
- Webb, R. C., et al. Ultrathin conformal devices for precise and continuous thermal characterization of human skin (vol 12, pg 938). Nat Mater. 12, 1078-1078 (2013).
- Yeo, W. H., et al. Multifunctional Epidermal Electronics Printed Directly Onto the Skin. Adv Mater. 25 (20), 2773-2778 (2013).
- Hattori, Y., et al. Multifunctional skin-like electronics for quantitative, clinical monitoring of cutaneous wound healing. Adv Healthc Mater. 3 (10), 1597-1607 (2014).
- Guo, S., DiPietro, L. A. Factors Affecting Wound Healing. J Dent Res. 89 (3), 219-229 (2010).
- Matzeu, G., et al. Skin temperature monitoring by a wireless sensor. Ieee Ind Elec. , 3533-3535 (2011).
- Cahill, D. G. Thermal-Conductivity Measurement from 30-K to 750-K – the 3-Omega Method. Rev Sci Instrum. 61 (2), 802-808 (1990).
- Fan, J. A., et al. Fractal Design Concepts for Stretchable Electronics. Nature Commun. 5 (3266), (2013).
- Song, Y. M., et al. Digital cameras with designs inspired by the arthropod eye. Nature. 497 (7447), 95-99 (2013).
- Jeong, J. W., et al. Capacitive Epidermal Electronics for Electrically Safe, Long-Term Electrophysiological Measurements. Adv Healthc Mater. 3 (5), 642-648 (2013).
- Zhang, Y. H., et al. Experimental and Theoretical Studies of Serpentine Microstructures Bonded To Prestrained Elastomers for Stretchable Electronics. Adv Funct Mater. 24 (14), 2028-2037 (2014).
- Carlson, A., Bowen, A. M., Huang, Y. G., Nuzzo, R. G., Rogers, J. A. Transfer Printing Techniques for Materials Assembly and Micro/Nanodevice Fabrication. Adv Mater. 24 (39), 5284-5318 (2012).
- Yeo, W. H., Webb, R. C., Lee, W., Jung, S., Rogers, J. A. Bio-integrated electronics and sensor systems. Proc Spie. 8725, (2013).
- Chung, H. J., et al. Fabrication of Releasable Single-Crystal Silicon–Metal Oxide Field-Effect Devices and Their Deterministic Assembly on Foreign Substrates. Adv Funct Mater. 21 (16), 3029-3036 (2011).
- Kim, H. S., et al. Unusual strategies for using indium gallium nitride grown on silicon (111) for solid-state lighting. Proc Natl Acad Sci U.S.A. 108 (25), 10072-10077 (2011).
- Padilla-Medina, J. A., et al. Assessment technique for acne treatments based on statistical parameters of skin thermal images. J Biomed Opt. 19 (4), 046019-046019 (2014).
