Name: fabrication and characterization of a conformal skin-like electronic system for quantitative, cutaneous wound management
Uploaded: 2015-09-02T14:00:00.000+00:00
Duration: 8 min 50 s
Description: Watch this Scientific Journal Video about Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management at JoVE.com

이 작품은 공학부, 버지니아 커먼 웰스 대학과 전자 장치의 일부 라이트 버지니아 마이크로 일렉트로닉스 센터의 미세 시설에서 제조되었다에서 시작 기금에 의해 지원되었다. 우리는 게시 된 기사 (10)로부터 획득 장치 및 임상 데이터 (이 논문의 그림 3 및 5)에 대한 공헌을 한 연구자를 인정합니다. 주문 제작, 데이터 기록 소프트웨어 W.-HY 덕분 요시아키 핫토리.

장치 제조, 피부 적층, 및 특성에 대한 실험은 그림 1, 2에 나타낸, 4 버지니아 커먼 웰스 대학 (VCU), 리치몬드, 버지니아, 미국에서 바이오 인터페이스 나노 공학 연구실에서 수행이 자원 봉사자 모두를 포함했다. 이 연구는 VCU 임상 시험 심사위원회의 승인 (프로토콜 번호 : HM20001454)와 VCU 인간 연구에서 연구 지침을 따랐다. 임상 시험 심사위원회, 노스 웨스턴 대학, 시카고, 일리노이, 미국에 의해 승인 : (STU69718 수) 그림 3과 5의 장치 및 임상 데이터는 환자의 실험 프로토콜에 따라 수행되었다 게시 된 기사 (10)로부터 획득했다. 1. 디바이스 제조 참고 :도 2는 전체적인 제조 공정에 대한 개략도를 나타낸다. <ol><li> 캐리어 기판을 제조<ol><li> 다이아몬드 블레이드를 이용하여 전자 제품의 원하는 크기로 베어 3 실리콘 (SI), 웨이퍼를 잘라. 참고 : 약 절반 Si 웨이퍼는 상처 장치에 이상적인 크기를 제공합니다. </li><li> 아세톤 및 아이소 프로필 알코올 (IPA)과 Si 웨이퍼를 탈지. 탈 (DI) 물과 웨이퍼를 헹구고 나서, 질소로 건조하고 3 분 동안 110 ° C에서 열판에 탈수. </li><li> (10) 폴리 디메틸 실록산 (PDMS)의 혼합물 11g 제조 : 1 부피 기준의 비율과 경화제 및 시간 동안 진공 챔버에서 탈기 혼합물. 주 : PDMS가 건조 패턴의 검색을 위해 사용되며, 습식 화학 (아세톤) 이전 연구 7에서 기반 접근하는 것이 바람직하다 미세 가공, 인쇄 후 전송된다. </li><li> 스핀 코팅 한 5 분 동안 3,000 rpm에서 웨이퍼상의 PDMS 혼합 용액 g과 완전히 30 분 동안 150 ℃에서 핫 플레이트상에서 경화. </li></ol></li><li> 예금 소재와 패턴 전자 <ol><li> PDMS-C 치료자외선 (UV)과 oated 웨이퍼 표면의 친수성을 만들기 위해 3 분 동안 UV 램프 (8.9 mW의 / cm 2)을 사용하여 / 오존. 참고 : 친수성 ​​표면이 PDMS에 대한 자세한 층의 균일 한 코팅을 제공합니다. </li><li> Spincoat 폴리이 미드 (PI; 2 ㎖)을 5 분 동안 150 ℃에서 핫 플레이트상에서 1.2 μm의 두께의 층, 프리 베이크를 형성하기 위해 1 분 동안 4,000 rpm에서, 피펫에 의해, 웨이퍼를 코팅 된 PDMS 및 사후에 2 시간 동안 250 ℃에서 굽는다. </li><li> 입금 크롬 (CR)를 20 nm 두께의 층을 형성 한 후 전자빔 (e-beam) 증착을 이용하여 3 ㎛의 두께로 층을 형성하기 위해 구리 (Cu)를 증착하기 (기본 압력 : ~ 1 × 10-7 토르 증착 압력 : ~ 1 × 10-6 토르, 증착 속도 : 1 - 5 / s). 증발기에 매립 증착 제어기 인터페이스에 의해 막 두께를 모니터링. 참고 : 구리 층의 두께가 얇은 소자 및 CR 층의 마이크로 저항에 충분한 전기 전도도의 레벨을 제공한다(PI) 및 Cu 사이의 접착을 촉진하는 데 사용됩니다. </li><li> 10 초 동안 900 rpm으로 세 단계, 60 초 동안 1100 rpm으로 20 초 동안 4,000 RPM으로 포토 레지스트 (2 ml)에 Spincoat 한 다음 30 분 동안 75 ℃에서 핫 플레이트상에서 그것을 경화. 주 : 상기 순차 단계는 두꺼운 (&gt; 10 μm의) 포토 레지스트를 증착하기 위해 사용되었다. </li><li> 구리 전자 패턴 (센서; 프랙탈 &#39;아노&#39;설계 폭 및 인터커넥트들에이 35㎛로, 구불 구불 한 오픈 메쉬 디자인을 폭 50㎛의 사용)에 맞추고 Si 웨이퍼의 중심에서 UV 노광 장치를 사용하여 (전력 10 mW의 / 초) 노출 시간 (25)와 함께 사용. 주 : 프랙탈 구조는 단지 사행 특징 14에 비해 우수한 기계적 신축성을 제공하기 위해 사용된다. </li><li> , 분 (개발자 및 DI 워터 2 비율 1) 탈 물로 씻어, 질소 건조 희석베이스 개발자에 포토 레지스트를 개발한다. 마이크로를 사용하여 패턴 (구리 도형 및 상호 연결)​​을 검사범위는 기능의 크기를 확인하고 미립자에서 결함을 찾을 수 있습니다. 참고 : 원치 않는 결함이있는 경우, 아세톤 / IPA / 탈 이온수로 세척하여 포토 레지스트를 제거합니다. 질소로 건조시킨 후, 1.2.4에서 1.2.6로 단계를 반복합니다. </li><li> ~ 6 분 동안 습식 화학 에칭 제에 침지하여 실리콘 웨이퍼상의 Cu 층을 에칭 (10 ㎖ 1의 비율과 황산 암모늄 및 물의 혼합물 : 4, 40 ° C에서 8 ㎚ / 초의 에칭 속도), 세정 DI 물과 질소로 건조와. 어떤을 통해 에칭 패턴 현미경을 사용하여 패턴을 검사합니다. 참고 : 패턴을 통해 에칭하는 경우,이 장치의 처리 및 세척 과정에서 기계적인 파괴로 이어질 수있는 기능, 원치 않는 날카로운 모서리의 원인이 될 수 있습니다. 종래 테스트 결과는 오버 에칭 원래 패턴의 이상 ~ 20 % 미만은 상기 문제를 일으킨 것으로 나타났다. </li><li> 300 mTorr의 전력 : 200 W, CF 4 가스 : 5 초 압력 반응성 이온 에칭 (RIE와의 Cr 층을 에칭CCM, O 2 가스 : 10 SCCM) 5 분. 패턴을 검사합니다. 주 : CR 층의 에칭, RIE 처리가 Cu 층으로 불리한 반응을 일으키는 화학 습식 에칭하는 것이 바람직하다. </li><li> 각각의 웨이퍼를 아세톤 (10 ㎖), IPA (10 ml)에 용해시키고, DI 물 (20 ml)에 침지시켜 금속층에 남아 포토 레지스트를 제거한다. 그런 다음, 질소로 건조. </li><li> Spincoat PI 피펫에 의해 금속 증착 웨이퍼 (2 ㎖), 4000 rpm에서 1 분 동안 5 분 동안 150 ℃에서 핫 플레이트상에서 1.2 μm의 두께의 층, 프리 베이크를 형성하고, 포스트 베이크의하기 2 시간 동안 250 ℃로. </li><li> 10 초 동안 900 rpm으로 세 단계, 60 초 동안 1100 rpm으로 20 초 동안 4,000 RPM으로 포토 레지스트 (2 ml)에 Spincoat 한 다음 30 분 동안 75 ℃에서 핫 플레이트상에서 그것을 경화. </li><li> 구리 전자를 캡슐화 PI 패턴을 맞 춥니 다 (센서, 폭과 인터커넥트에 35 μm의 프랙탈 &#39;페 아노&#39;디자인 250와 뱀 오픈 메쉬 디자인노출 시간 25 초 10 mW의 / 초) : UV 노광 장치 (전원을 이용하여 미리 정의 된 도형 및 구리 배선과 μm의 폭). </li><li> , 분 (개발자 및 DI 워터 2 비율 1) 탈 물로 씻어, 질소 건조 희석 개발자와 포토 레지스트를 개발한다. 피처 크기를 확인하고, 미립자로부터 결함을 찾기 위해 현미경을 사용하는 패턴을 검사한다. 참고 : 원치 않는 결함이있는 경우, 아세톤 / IPA / 탈 이온수로 세척하여 포토 레지스트를 제거합니다. 질소로 건조시킨 후, 1.2.10에서 1.2.13로 단계를 반복합니다. </li><li> 25 분 동안 RIE (20 SCCM : 170 mTorr로, 전력 : 150 W, O 2 가스 압력)와 PI 층을 에칭. 패턴을 검사합니다. </li><li> 각각의 웨이퍼를 아세톤 (10 ㎖), IPA (10 ml)에 용해시키고, DI 물 (20 ml)에 침지하여 포토 레지스트를 제거 남아. 그런 다음, 질소로 건조. </li></ol></li><li> 탄성 막을 준비 <ol><li> 실리콘 혼합물 (1 캡슐화 10g을 준비한다 :1 볼륨베이스와 경화제의 비)와 적외선 카메라를 사용하여 피부에 온도 변화의 제어를 용이하게 측정하는 12시 59분 부피비로 흑색 잉크 (15)를 추가한다. 참고 : 사용되는 실리콘 (투명 캡슐 고무) 장치 (16)에 낮은 점도, 광학 선명도, 전기 절연 / 보호의 고유 한 특성을 제공한다. </li><li> 1 분 동안 150 rpm으로 배양 접시에서 혼합물의 Spincoat 8g / O를위한 N을 실온에서 500 μm의 두께 탄성 막과 치료를 형성한다. 주 : 재료가 균일 한 두께에 대한 평평한 표면에 배치 할 필요가있다. </li><li> 날카로운 면도날을 사용하여 X 30mm 70mm의 원하는 크기로 막 잘라 부드럽게 페트리 접시에서 분리. </li></ol></li><li> 검색 및 전자 전송 <ol><li> 수용성 테이프 (25mm X 80mm)를 잘라 제작 된 전자 패턴에 적층 부드럽게 및 130 ° C에서 열판에 배치3 분. 주 : 온도 상승 표면으로부터 전자 패턴의 분리 도와 Si 웨이퍼상의 PDMS 층을 확대. </li><li> 전자 패턴을 검색하기 위해 PDMS / 실리콘 웨이퍼로부터 빠르게 테이프를 분리. </li><li> 석출 20 ㎚의 전자 빔 증착법에 의해 검색 패턴에 50 nm 두께의 이산화 실리콘 (SiO2) 뒤에 CR (접착) 두께. </li><li> 표면을 활성화하기 위해 2 분 동안 타겟 실리콘 막에 UV 램프 (365 nm의, 8.9 mW의 / cm 2)을 이용하여 UV / 오존 처리한다. </li><li> 원하는 위치에 테이프 검색 패턴을 배치하고 고르게 기판까지 패턴의 상단 측으로부터 압력을 가하여 실리콘 막에 패턴을 전송. 5 분 동안 테이프를 용해 물을 뿌려야 함. 참고 자료 전송 한 처리가 공유 결합 (SI-O-시)에 의해 촉진되어 증착 된 실리콘 이산화물 및 UV 활성화 된 실리콘 기판 (17) 사이 </s&gt;까지. </li><li> 껍질은 테이프 떨어져, 1 분 동안 90 ° C에서 열판에 탈 이온수, 건조 씻어. </li></ol></li><li> 실리콘 막을 사용하여 장치를 캡슐화 <ol><li> (: 염기의 부피비 1 및 경화제 1) 실리콘 혼합물을 캡슐화 10g을 준비한다. </li><li> 패드 실리콘 코팅을 피하기 위해 하부 실리콘 막과 반 데르 발스 결합, PDMS에 의해 직사각형 부재 (22 × 6 × 1mm 3)와 케이블 접촉 패드 커버. </li><li> 4,000 rpm에서 실리콘 혼합물 5g Spincoat 1 분 이전에 전자 5 μm의 두께 층을 형성하기위한 다음 / O 동안 실온에서 N을 치료. </li></ol></li><li> 데이터 수집을위한 유연한 리본 케이블을 연결합니다 <ol><li> 깨끗한 표면을 3 초 동안 커넥터 패드, 피펫 팅에 의해 용강 플럭스 (0.5 ml)에 적용됩니다. </li><li> 고온에서의 압력과 접점에 얇은 플렉시블 리본 케이블을 결합 (&gt; 60 ° C). 일반적인 헤어 straightener은 취급이 용이하고 결합을 제공합니다. 주 : 마이크로 필름 케이블 실리콘에 전사 된 금속 막의 기계적 파괴를 피하기 위해, 종래의 하드 와이어 납땜하는 것이 바람직하다. </li><li> 디지털 멀티 미터를 사용하여 전기적 연결을 확인합니다. (~ 1cm 이격 거리)의 저항 값이 일단 센서 패드와 필름 케이블의 다른 쪽 끝 사이에 1 Ohm 미만 예상된다. </li><li> 단계 1.6.2에서 설명 된 것과 동일한 전략을 정의 인쇄 회로 기판에 리본 케이블의 다른 쪽 끝의 접합. </li><li> 디지털 멀티 미터를 사용하여 전기적 연결을 확인합니다. </li><li> PCB에 종래의 와이어를 납땜 데이터 수집 하드웨어 장치를 연결한다. </li></ol></li></ol> 2. 임상 시험 <ol><li> 소독액을 사용하여 장치 청소 <ol><li> (: 물 및 솔루션의 1 부피비 40) 희석 된 소독제 용액 205g을 준비합니다. </li><li> 스프레이장치의 용액 (10 g) 및 10 분 동안 담가. 참고 : 희석 된 살균 청소기 실온에서 저장 될 수있다. </li><li> 물에 세 번 헹구고 깨끗한 조직으로 건조. </li></ol></li><li> 디바이스 테스트에 대한 장비의 시리즈 셋업 <ol><li> 준비 및 전류원, 멀티플렉서, 및 데이터 기록을위한 노트북 컴퓨터에 설치된 소프트웨어와 함께 지정 잠금 증폭기를 연결한다. </li><li> 삼각대에 적외선 카메라를 놓고 참고로 온도 측정의 대상 객체에 초점을 맞추고있다. </li><li> 잠금에 앰프의 설정 시스템 매개 변수는 열전도도 측정 (주파수 : 1 3 Hz에서, 시간을 일정 : 3, 1 초, 감도 : 1 MV, 동적 예약 : 높은 예비) 및 온도 (주파수 : 997 Hz에서, 시간을 상수 : 300 밀리 초, 감도 : 2 MV, 동적 예약 : 저소음) 적용 정전류 (2 엄마와 함께). </li><li> 미세 및 전송 인쇄에 의해 준비되고 상처에 장착 된 두 개의 상처 장치를 연결하고오른쪽 환자로부터 데이터를 기록하기 전에 멀티플렉서 반대측 사이트. </li></ol></li><li> 레코드 온도 및 열전도 주 : 데이터 수집 소프트웨어가 원격 로크의 실시간 모니터링 및 데이터 저장을위한 증폭기를 제어 할 수있는 주문 제작된다. 온도 측정에있어서, 각 데이터 포인트는 20 초마다 300 밀리 초를 측정한다. 처음 10 초 및 다음 10 초 동안 데이터의 세트는 각각의 평균 온도 값과 표준 편차를 계산하는 데 사용된다. 기록 된 데이터는 적외선 열 화상 데이터와 비교 한 그래프를 플롯하는 데 사용되는 쉼표로 구분 된 값 파일로 저장됩니다. 열전도율의 측정에있어서, 3Ω 신호는 다음 분석적 직접적 열전도를 계산하는 데 이용되는 하드웨어 화면 (증폭기)로부터 판독된다. <ol><li> 조심스럽게 살균 알코올을 사용하여 피부에 장치 응용 프로그램 사이트 (10)를 쳐 문질러. </li><li> 2.3.2) 부드럽게 소프트 결합을 용이하게하기 위하여 손가락 피부에 장치를 눌러 원하는 피부 위치에 두 장치 라미네이트 수술 상처 부위에 하나 및 기준으로서 반대측의 위치에 다른. </li><li> 데이터 수집을 시작하여 장치의 열전도율에 관련된 전기 전압 (3Ω)를 측정. </li><li> 피부에 장치의 등각 접촉을 확인 얻어진 데이터를 평가; 이상 값 (&lt;0.1 ​​W는 / mK의)는 장치의 접촉 불량을 보여줍니다. </li><li> 커스텀 소프트웨어를 통해 온도 분포 및 기록 데이터를 결정하는 전기 저항을 측정한다. </li><li> 피부에 두 장치의 광학 및 적외선 이미지를 가져 가라. </li><li> 권취 장치 (2.3.5)에서 기록 된 데이터와 이미지에서 IR 온도 값을 비교한다. 사용자 정의 스프레드 시트의 열을 구분하는 데 두 값을 추가합니다. </li></ol></li><li> 기록 된 데이터를 분석 <ol><li> 에 기록 된 데이터를 내보내기자동 장치에서 센서의 배열에서 온도 및 열전도율을 계산 템플릿을 정의. </li><li> 한달에 걸쳐 비교 데이터 (온도와 다른 시간 스케일 센서 위치에 따라 열전도율) (네 일 1, 3, 15의 데이터 세트 및 30)을 플롯. </li><li> 온도와 시간에 따른 열전도 일련의 데이터를 비교하여 데이터를 분석; 급격한 상승과 값 또는 상처 부위에 상처 치유 단계 및 / 또는 예기치 않은 이상의 변화를 말해 놓습니다. </li></ol></li></ol>

<ol>
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A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+Affecting+Wound+Healing.">Factors Affecting Wound Healing.</a> J Dent Res. 89 (3), 219-229 (2010).</li><li>Matzeu, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Skin+temperature+monitoring+by+a+wireless+sensor.">Skin temperature monitoring by a wireless sensor.</a> Ieee Ind Elec. , 3533-3535 (2011).</li><li>Cahill, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thermal-Conductivity+Measurement+from+30-K+to+750-K+-+the+3-Omega+Method.">Thermal-Conductivity Measurement from 30-K to 750-K - the 3-Omega Method.</a> Rev Sci Instrum. 61 (2), 802-808 (1990).</li><li>Fan, J. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fractal+Design+Concepts+for+Stretchable+Electronics.">Fractal Design Concepts for Stretchable Electronics.</a> Nature Commun. 5 (3266), (2013).</li><li>Song, Y. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Digital+cameras+with+designs+inspired+by+the+arthropod+eye.">Digital cameras with designs inspired by the arthropod eye.</a> Nature. 497 (7447), 95-99 (2013).</li><li>Jeong, J. 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A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transfer+Printing+Techniques+for+Materials+Assembly+and+Micro/Nanodevice+Fabrication.">Transfer Printing Techniques for Materials Assembly and Micro/Nanodevice Fabrication.</a> Adv Mater. 24 (39), 5284-5318 (2012).</li><li>Yeo, W. H., Webb, R. C., Lee, W., Jung, S., Rogers, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bio-integrated+electronics+and+sensor+systems.">Bio-integrated electronics and sensor systems.</a> Proc Spie. 8725, (2013).</li><li>Chung, H. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fabrication+of+Releasable+Single-Crystal+Silicon&#8211;Metal+Oxide+Field-Effect+Devices+and+Their+Deterministic+Assembly+on+Foreign+Substrates.">Fabrication of Releasable Single-Crystal Silicon&#8211;Metal Oxide Field-Effect Devices and Their Deterministic Assembly on Foreign Substrates.</a> Adv Funct Mater. 21 (16), 3029-3036 (2011).</li><li>Kim, H. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Unusual+strategies+for+using+indium+gallium+nitride+grown+on+silicon+(111)+for+solid-state+lighting.">Unusual strategies for using indium gallium nitride grown on silicon (111) for solid-state lighting.</a> Proc Natl Acad Sci U.S.A. 108 (25), 10072-10077 (2011).</li><li>Padilla-Medina, J. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+technique+for+acne+treatments+based+on+statistical+parameters+of+skin+thermal+images.">Assessment technique for acne treatments based on statistical parameters of skin thermal images.</a> J Biomed Opt. 19 (4), 046019-046019 (2014).</li></ol>

The authors declare that they have no competing financial interests.

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...

임상 연구 및 생물 의학 연구에서, 상처 치유의 모니터링은 상처 1,2의 조직 형태 학적 변화의 조직 학적 평가를 기반으로하는 침습적 방법에 초점을 맞추고있다. 최근, 전자 기술의 급속한 발전을 육안 또는 디지털 촬상 3,4- 공 초점 주사 현미경 및 분광기를 통해 프로세스 4,5- 상처 치유를 검사 할 수 고정밀 영상 및 분석 도구의 개발을 가능하게한다. 그러나, 이러한 접근법은 촬상 높은 비용, 복잡한 광학 도구 및 조작이 필요하며, 더욱 중요하게는, 환자는 시험 중에 고정화 할 필요가있다. 따라서,보다 정확한 상처 관리를 제공하기 쉬운, 비 침습성 정량 저렴하고있는 새로운 다기능 장치 및 시스템에 대한 요구가 존재한다. 여기서는 온도 및 열 condu 정확한 실시간 매핑을 제공 피부 같은 전자 시스템을 소개ctivity과 비 침습적 장치의 등각 적층 통하여 상처 부위에서 가열의 정확한 수준을 제공한다. 이 장치는 표피 6-9의 기술, 기계 및 재료 특성에 맞도록 설계되어 피부 표피 장착형 전자 시스템 (굽힘 강성, 총 두께, 유효 계수, 질량 밀도)의 클래스를 나타낸다. 이 장치는 생체 적합성, 피부 친화적 인, 방수 설계, 세척 환자 (10)에 임상 응용 프로그램에 대한 소독 할 수있는 재사용 가능한 형태이다. 상처 조직 근처에 장착 등각 전자 장치는 수분에 상관 온도 (8)와 열 전도율 (13)의 양적 기록을 통해, 상처 11,12 증가 혈류량과 효소 반응에 의한 염증 단계 (상처 치유 과정의 하나), 캡처 . 실험 및 계산 연구 accommod하는 역학 최적 설계를 결정자연의 움직임을 먹고 기계 파괴하지 않고 균주를 적용하고 고 충실도 신호의 획득을 제공하는 피부 표면에 등각 라미네이트 피부와 같은 전자 기계 스트레칭의 기본 물리학을 캡처합니다. 이 문서에서 설명하는 프로토콜은 장치 청소, 임상 설정에서 장비 설정 및 피부 상처에 온도와 열전도도의 정량적 모니터링을위한 임상 응용 프로그램을 포함하여 준비 테스트, 피부와 같은 전자 시스템에 대한 마이크로의 방법을 제시한다.

<table><tbody><tr><td>3&quot; Silicon wafer</td><td>University Wafer, USA</td><td></td><td>Use as carrier to fabricate the device</td></tr><tr><td>Acetone</td><td>Fisher Scientific, USA</td><td>A18-1</td><td>Use to clean a wafer and to remove photoresist</td></tr><tr><td>Isopropanol (IPA)</td><td>Fisher Scientific, USA</td><td>A459-1</td><td>Use to clean a wafer</td></tr><tr><td>AZ4620 photoresist</td><td>AZ Electrionic Materials, USA</td><td></td><td>Use to make patterns on metals and polymers</td></tr><tr><td>AZ400K developer</td><td>AZ Electrionic Materials, USA</td><td></td><td>Use to develop AZ4620 photoresist</td></tr><tr><td>Chromium etchant</td><td>Transene, USA</td><td>1020AC</td><td>Use to etch Cr layer of device</td></tr><tr><td>Copper etchant</td><td>Transene, USA</td><td>ASP-100</td><td>Use to etch Cu layer of device</td></tr><tr><td>Sylgard 184 Silicone Elastomer Kit (PDMS)</td><td>Dow Corning, USA</td><td>39100000</td><td>Use as a substrate for &#039;dry&#039; retrieval</td></tr><tr><td>PI2545 polyimide</td><td>HD MicroSystem, USA</td><td></td><td>Use to encapsulate metal layer</td></tr><tr><td>Solaris</td><td>Smooth-On, USA</td><td></td><td>Use as substrate and to encapsulate device</td></tr><tr><td>Petridish</td><td>Carolina, USA</td><td>741255</td><td>Use as mold to make substrate</td></tr><tr><td>Water-Soluble Wave Solder Tape 5414</td><td>3M, USA</td><td>AM000000217</td><td>Use to retrive device from PDMS layer</td></tr><tr><td>High Activity Liquid Stainless Steel Flux</td><td>Worthington, USA</td><td>331929</td><td>Use to remove oxidation layer on Cu</td></tr><tr><td>Flexible, micro-film cable</td><td>Elform, USA</td><td></td><td>Use to make the electrical connection between the electronic device and the data acquisition system</td></tr><tr><td>pH Neutral Cleaner</td><td>Australian Gold, USA</td><td></td><td>Use as disinfectant solution to clean device in clinical testing</td></tr><tr><td>Solder</td><td>Kester, USA</td><td>24-6337-9703</td><td>Use as material to solder hard wires</td></tr><tr><td>Ultraviolet lamp</td><td>Cole-Parmer, USA</td><td>97600-00</td><td>Use to activate PDMS layer as hydrophilic surface</td></tr><tr><td>Multiplexer</td><td>FixYourBoard, USA</td><td>U802</td><td>Use to acquire measurements from six sensing components&amp;nbsp;</td></tr><tr><td>DC/AC current source</td><td>Keithley, USA</td><td>6221</td><td>Use to supply current</td></tr><tr><td>SMD Digital Hot Air Rework Station</td><td>Aoyue, China</td><td>968A+</td><td>Use to solder hard wires, to electrically connect between the device and external instruments</td></tr><tr><td>Infrared camera</td><td>FLIR, USA</td><td>435-0001-01-00</td><td>Use to take infrared images in experiment</td></tr><tr><td>Digital multimeter</td><td>Fluke, USA</td><td>117</td><td>Use to check electrical connection</td></tr><tr><td>Lock-in amplifier</td><td>Stanford Research System, USA</td><td>SR830</td><td>Use to perform four-point-probe-measurement</td></tr><tr><td>Electron beam evaporator</td><td>9 scale Vacuum Products, USA</td><td></td><td>Use to deposit thin films (Cu and SiO&lt;sub&gt;2&lt;/sub&gt;)</td></tr></tbody></table>

fabrication and characterization of a conformal skin-like electronic system for quantitative, cutaneous wound management

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.

도 1은 환자에 양적, 피부 상처 관리 용으로 설계된 공형, 피부와 같은 전자 시스템의 특성의 개요를 나타낸다. 다기능 전자 장치는 마이크로 프랙탈 구조 3,14 구성 및 필라멘트 뱀 뛰어난 기계적인 신축성과 굽힘 성을 제공하는 얇은 탄성 중합체 막에 9,17 추적합니다. 완전히 실리콘 층에 의해 둘러싸인 호환 장치 혼자 반 데르 발스 상호 작용을 통해 피부에 부드러운,...

Watch this Scientific Journal Video about Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management at JoVE.com

Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management

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.

양적, 피부가 상처 관리를위한 등각 피부와 같은 전자 시스템의 제조 및 특성

Recent advances in the development of electronic technologies and biomedical devices offer opportunities for non-invasive, quantitative assessment of ...

fabrication-characterization-conformal-skin-like-electronic-system

Research

JoVE Journal

Bioengineering

8.8K 조회수.  Virginia Commonwealth University. 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. 

비디오: Fabrication and Characterization of a Conformal Skin-like Electronic System for Quantitative, Cutaneous Wound Management

Hollow Microneedle-based Sensor for Multiplexed Transdermal Electrochemical Sensing

The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals suffering from chronic medical conditions facile assessment of their immediate physiological state. Furthermore, it could serve as a research tool for analysis of complex, multifactorial medical conditions. In order for such a multianalyte sensor to be realized, it must be minimally invasive, sampling of interstitial fluid must occur without pain or harm to the user, and analysis must be rapid as well as selective.
Initially developed for pain-free drug delivery, microneedles have been used to deliver vaccines and pharmacologic agents (e.g., insulin) through the skin.1-2 Since these devices access the interstitial space, microneedles that are integrated with microelectrodes can be used as transdermal electrochemical sensors. Selective detection of glucose, glutamate, lactate, hydrogen peroxide, and ascorbic acid has been demonstrated using integrated microneedle-electrode devices with carbon fibers, modified carbon pastes, and platinum-coated polymer microneedles serving as transducing elements.3-7,8
This microneedle sensor technology has enabled a novel and sophisticated analytical approach for in situ and simultaneous detection of multiple analytes. Multiplexing offers the possibility of monitoring complex microenvironments, which are otherwise difficult to characterize in a rapid and minimally invasive manner. For example, this technology could be utilized for simultaneous monitoring of extracellular levels of, glucose, lactate and pH,9 which are important metabolic indicators of disease states7,10-14 (e.g., cancer proliferation) and exercise-induced acidosis.15

This article details the construction of a multiplexed microneedle-based sensor. The device is being developed for in situ sampling and electrochemical analysis of multiple analytes in a rapid and selective manner. We envision clinical medicine and biomedical research uses for these microneedle-based sensors.

다중 Transdermal 전기 감지를위한 빈 Microneedle 기반 센서

The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals ...

연구

생체공학

Bridging the Bio-Electronic Interface with Biofabrication

Advancements in lab-on-a-chip technology promise to revolutionize both research and medicine through lower costs, better sensitivity, portability, and higher throughput. The incorporation of biological components onto biological microelectromechanical systems (bioMEMS) has shown great potential for achieving these goals. Microfabricated electronic chips allow for micrometer-scale features as well as an electrical connection for sensing and actuation. Functional biological components give the system the capacity for specific detection of analytes, enzymatic functions, and whole-cell capabilities. Standard microfabrication processes and bio-analytical techniques have been successfully utilized for decades in the computer and biological industries, respectively. Their combination and interfacing in a lab-on-a-chip environment, however, brings forth new challenges. There is a call for techniques that can build an interface between the electrode and biological component that is mild and is easy to fabricate and pattern.
Biofabrication, described here, is one such approach that has shown great promise for its easy-to-assemble incorporation of biological components with versatility in the on-chip functions that are enabled. Biofabrication uses biological materials and biological mechanisms (self-assembly, enzymatic assembly) for bottom-up hierarchical assembly. While our labs have demonstrated these concepts in many formats 1,2,3, here we demonstrate the assembly process based on electrodeposition followed by multiple applications of signal-based interactions. The assembly process consists of the electrodeposition of biocompatible stimuli-responsive polymer films on electrodes and their subsequent functionalization with biological components such as DNA, enzymes, or live cells 4,5. Electrodeposition takes advantage of the pH gradient created at the surface of a biased electrode from the electrolysis of water 6,7,. Chitosan and alginate are stimuli-responsive biological polymers that can be triggered to self-assemble into hydrogel films in response to imposed electrical signals 8. The thickness of these hydrogels is determined by the extent to which the pH gradient extends from the electrode. This can be modified using varying current densities and deposition times 6,7. This protocol will describe how chitosan films are deposited and functionalized by covalently attaching biological components to the abundant primary amine groups present on the film through either enzymatic or electrochemical methods 9,10. Alginate films and their entrapment of live cells will also be addressed 11. Finally, the utility of biofabrication is demonstrated through examples of signal-based interaction, including chemical-to-electrical, cell-to-cell, and also enzyme-to-cell signal transmission. 
Both the electrodeposition and functionalization can be performed under near-physiological conditions without the need for reagents and thus spare labile biological components from harsh conditions. Additionally, both chitosan and alginate have long been used for biologically-relevant purposes 12,13. Overall, biofabrication, a rapid technique that can be simply performed on a benchtop, can be used for creating micron scale patterns of functional biological components on electrodes and can be used for a variety of lab-on-a-chip applications.

This article describes a biofabrication approach: deposition of stimuli-responsive polysaccharides in the presence of biased electrodes to create biocompatible films which can be functionalized with cells or proteins. We demonstrate a bench-top strategy for the generation of the films as well as their basic uses for creating interactive biofunctionalized surfaces for lab-on-a-chip applications.

Biofabrication와 바이오 전자 인터페이스 브리지

Advancements in lab-on-a-chip technology promise to revolutionize both research and medicine through lower costs, better sensitivity, portability, and ...

A Full Skin Defect Model to Evaluate Vascularization of Biomaterials In Vivo

Insufficient vascularization is considered to be one of the main factors limiting the clinical success of tissue-engineered constructs. In order to evaluate new strategies that aim at improving vascularization, reliable methods are required to make the in-growth of new blood vessels into bio-artificial scaffolds visible and quantify the results. Over the past couple of years, our group has introduced a full skin defect model that enables the direct visualization of blood vessels by transillumination and provides the possibility of quantification through digital segmentation. In this model, one surgically creates full skin defects in the back of mice and replaces them with the material tested. Molecules or cells of interest can also be incorporated in such materials to study their potential effect. After an observation time of one&#8217;s own choice, materials are explanted for evaluation. Bilateral wounds provide the possibility of making internal comparisons that minimize artifacts among individuals as well as of decreasing the number of animals needed for the study. In comparison to other approaches, our method offers a simple, reliable and cost effective analysis. We have implemented this model as a routine tool to perform high-resolution screening when testing vascularization of different biomaterials and bio-activation approaches.

A Full Skin Defect Model to Evaluate Vascularization of Biomaterials In Vivo

Vascularization is key to approaches in successful tissue engineering. Therefore, reliable technologies are required to evaluate the development of vascular networks in tissue-constructs. Here we present a simple and cost-effective method to visualize and quantify vascularization in vivo.

전체 피부 결함 모델은 생체의 혈관 신생을 평가하기<em&gt; 생체</em

Insufficient vascularization is considered to be one of the main factors limiting the clinical success of tissue-engineered constructs. In order to ...

Generation of a Three-dimensional Full Thickness Skin Equivalent and Automated Wounding

In vitro models are a cost effective and ethical alternative to study cutaneous wound healing processes. Moreover, by using human cells, these models reflect the human wound situation better than animal models. Although two-dimensional models are widely used to investigate processes such as cellular migration and proliferation, models that are more complex are required to gain a deeper knowledge about wound healing. Besides a suitable model system, the generation of precise and reproducible wounds is crucial to ensure comparable results between different test runs. In this study, the generation of a three-dimensional full thickness skin equivalent to study wound healing is shown. The dermal part of the models is comprised of human dermal fibroblast embedded in a rat-tail collagen type I hydrogel. Following the inoculation with human epidermal keratinocytes and consequent culture at the air-liquid interface, a multilayered epidermis is formed on top of the models. To study the wound healing process, we additionally developed an automated wounding device, which generates standardized wounds in a sterile atmosphere.

The goal of this protocol is to build up a three-dimensional full thickness skin equivalent, which resembles natural skin. With a specifically constructed automated wounding device, precise and reproducible wounds can be generated under maintenance of sterility.

3 차원 전체 두께 피부의 세대 동등한 및 자동화 부상

In vitro models are a cost effective and ethical alternative to study cutaneous wound healing processes. Moreover, by using human cells, these models ...

A Simple and Scalable Fabrication Method for Organic Electronic Devices on Textiles

Today, wearable electronics devices combine a large variety of functional, stretchable, and flexible technologies. However, in many cases, these devices cannot be worn under everyday conditions. Therefore, textiles are commonly considered the best substrate to accommodate electronic devices in wearable use. In this paper, we describe how to selectively pattern organic electroactive materials on textiles from a solution in an easy and scalable manner. This versatile deposition technique enables the fabrication of wearable organic electronic devices on clothes.

In this paper, we present a protocol to selectively deposit organic materials on textiles, which allows for the direct integration of organic electronic devices with wearables. The fabricated devices can be fully integrated in textiles, respecting their mechanical appearance and enabling sensing capabilities.

섬유에 유기 전자 장치를위한 간편하고 확장 가능한 제조 방법

Today, wearable electronics devices combine a large variety of functional, stretchable, and flexible technologies. However, in many cases, these devices ...

Human Ex vivo Wound Model and Whole-Mount Staining Approach to Accurately Evaluate Skin Repair

Chronic non-healing wounds, which primarily affect the elderly and diabetic, are a significant area of clinical unmet need. Unfortunately, current chronic wound treatments are inadequate, while available pre-clinical models poorly predict the clinical efficacy of new therapies. Here we describe a high throughput, pre-clinical model to assess multiple aspects of the human skin repair response. Partial thickness wounds were created in human ex vivo skin and cultured across a healing time course. Skin wound biopsies were collected in fixative for the whole-mount staining procedure. Fixed samples were blocked and incubated in primary antibody, with detection achieved via fluorescently conjugated secondary antibody. Wounds were counterstained and imaged via confocal microscopy before calculating percentage wound closure (re-epithelialization) in each biopsy. Applying this protocol, we reveal that 2 mm excisional wounds created in healthy donor skin are fully re-epithelialized by day 4-5 post-wounding. On the contrary, closure rates of diabetic skin wounds are significantly reduced, accompanied by perturbed barrier reformation. Combining human skin wounding with a novel whole-mount staining approach allows a rapid and reproducible method to quantify ex vivo wound repair. Collectively, this protocol provides a valuable human platform to evaluate the effectiveness of potential wound therapies, transforming pre-clinical testing and validation.

Here we demonstrate an optimized technique for assessing wound repair using ex vivo human skin combined with a whole-mount staining approach. This methodology provides a pre-clinical platform for the evaluation of potential wound therapies.

인간 Ex 생체 내 상처 모델 및 피부 수리를 정확하게 평가하기 위한 전산 염색 접근법

Chronic non-healing wounds, which primarily affect the elderly and diabetic, are a significant area of clinical unmet need. Unfortunately, current chronic ...

발생학

Generation of Self-assembled Vascularized Human Skin Equivalents

Human skin equivalents (HSEs) are tissue engineered constructs that model epidermal and dermal components of human skin. These models have been used to study skin development, wound healing, and grafting techniques. Many HSEs continue to lack vasculature and are additionally analyzed through post-culture histological sectioning which limits volumetric assessment of the structure. Presented here is a straightforward protocol utilizing accessible materials to generate vascularized human skin equivalents (VHSE); further described are volumetric imaging and quantification techniques of these constructs. Briefly, VHSEs are constructed in 12 well culture inserts in which dermal and epidermal cells are seeded into rat tail collagen type I gel. The dermal compartment is made up of fibroblast and endothelial cells dispersed throughout collagen gel. The epidermal compartment is made up of keratinocytes (skin epithelial cells) that differentiate at the air-liquid interface. Importantly, these methods are customizable based on needs of the researcher, with results demonstrating VHSE generation with two different fibroblast cell types: human dermal fibroblasts (hDF) and human lung fibroblasts (IMR90s). VHSEs were developed, imaged through confocal microscopy, and volumetrically analyzed using computational software at 4- and 8-week timepoints. An optimized process to fix, stain, image, and clear VHSEs for volumetric examination is described. This comprehensive model, imaging, and analysis techniques are readily customizable to the specific research needs of individual labs with or without prior HSE experience.

The goal of this protocol is to describe the generation and volumetric analysis of vascularized human skin equivalents using accessible and simple techniques for long term culture. To the extent possible, the rationale for steps is described to allow researchers the ability to customize based on their research needs.

자가 조립 혈관 인체 피부 등가물의 생성

Human skin equivalents (HSEs) are tissue engineered constructs that model epidermal and dermal components of human skin. These models have been used to ...

Generation of a Simplified Three-Dimensional Skin-on-a-chip Model in a Micromachined Microfluidic Platform

This work presents a new, cost-effective, and reliable microfluidic platform with the potential to generate complex multilayered tissues. As a proof of concept, a simplified and undifferentiated human skin containing a dermal (stromal) and an epidermal (epithelial) compartment has been modelled. To accomplish this, a versatile and robust, vinyl-based device divided into two chambers has been developed, overcoming some of the drawbacks present in microfluidic devices based on polydimethylsiloxane (PDMS) for biomedical applications, such as the use of expensive and specialized equipment or the absorption of small, hydrophobic molecules and proteins. Moreover, a new method based on parallel flow was developed, enabling the in situ deposition of both the dermal and epidermal compartments. The skin construct consists of a fibrin matrix containing human primary fibroblasts and a monolayer of immortalized keratinocytes seeded on top, which is subsequently maintained under dynamic culture conditions. This new microfluidic platform opens the possibility to model human skin diseases and extrapolate the method to generate other complex tissues.

Here, we present a protocol to generate a three-dimensional simplified and undifferentiated skin model using a micromachined microfluidic platform. A parallel flow approach allows the in situ deposition of a dermal compartment for the seeding of epithelial cells on top, all controlled by syringe pumps.

마이크로머신 마이크로유체 플랫폼의 간소화된 3차원 스킨 온-어칩 모델 생성

This work presents a new, cost-effective, and reliable microfluidic platform with the potential to generate complex multilayered tissues. As a proof of ...

Conformable Wearable Electrodes: From Fabrication to Electrophysiological Assessment

Wearable electronic devices are becoming key players in monitoring the body signals predominantly altered during physical activity tracking. Considering the growing interest in telemedicine and personalized care driven by the rise of the Internet of Things era, wearable sensors have expanded their field of application into healthcare. To ensure the collection of clinically relevant data, these devices need to establish conformable interfaces with the human body to provide high-signal-quality recordings and long-term operation. To this end, this paper presents a method to easily fabricate conformable thin tattoo- and soft textile-based sensors for their application as wearable organic electronic devices in a broad spectrum of surface electrophysiological recordings. 
The sensors are developed through a cost-effective and scalable process of cutaneous electrode patterning using poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS), the most popular conductive polymer in bioelectronics, on off-the-shelf, wearable substrates. This paper presents key steps in electrode characterization through impedance spectroscopy to investigate their performance in signal transduction when coupled with the skin. Comparative studies are required to position the performance of novel sensors with respect to the clinical gold standard. To validate the fabricated sensors' performance, this protocol shows how to perform various biosignal recordings from different configurations through a user-friendly and portable electronic setup in a laboratory environment. This methods paper will allow multiple experimental initiatives to advance the current state of the art in wearable sensors for human body health monitoring.

Two recent technologies-tattoo and textiles-have demonstrated promising results in cutaneous sensing. Here, we present the fabrication and evaluation methods of tattoo and textile electrodes for cutaneous electrophysiological sensing. These electronic interfaces made of conductive polymers outperform the existing standards in terms of comfort and sensitivity.

적합성 웨어러블 전극: 제작에서 전기생리학적 평가에 이르기까지

Wearable electronic devices are becoming key players in monitoring the body signals predominantly altered during physical activity tracking. Considering ...

Development of a Benchtop Model for Evaluating the Compatibility of Wound Dressing Materials with Negative Pressure Wound Therapy Systems

Negative pressure wound therapy (NPWT) systems facilitate wound healing by applying sub-atmospheric pressure to the wound bed, which promotes granulation tissue formation and reduces inflammation. Wound dressings can be used with these systems to enhance healing; however, the effects of dressings on NPWT device performance are challenging to assess. The purpose of this study was to develop a benchtop flesh analog model for testing the compatibility of wound dressing materials with NPWT devices. In this study, a chitosan-based advanced wound care device was evaluated for its effects on NPWT performance under maximum and minimum therapy pressures. The goal was to use the model to compare pressure readings and fluid collection for samples with and without the chitosan wound care device. The benchtop model was constructed using a plastic box connected to multiple pressure gauges. A circular defect was created on a piece of pork belly, used as the flesh analog, and inserted into the box. The defect was filled with standard NPWT foam or foam combined with the wound dressing. Simulated body fluid containing bovine serum was added to the box, which was then tested at either maximum (-200 mmHg) or minimum (-25 mmHg) pressures for 72 h. Pressure and fluid collection were recorded every 12 h. The NPWT system successfully maintained pressure over the 72 h test period, both with and without the test dressings. The addition of the wound dressings did not impact fluid collection. The test box proved effective as a benchtop model, as it could be sealed and maintained vacuum conditions over the 72 h testing period. This model successfully demonstrated its utility in evaluating the compatibility of wound dressing materials with NPWT systems.

This study presents a benchtop model designed to evaluate the compatibility of wound dressing materials with negative pressure wound therapy systems by assessing pressure and fluid collection over 72 h under continuous and intermittent pressure settings.

상처 드레싱 재료와 음압 상처 치료 시스템의 호환성을 평가하기 위한 벤치탑 모델 개발

Negative pressure wound therapy (NPWT) systems facilitate wound healing by applying sub-atmospheric pressure to the wound bed, which promotes granulation ...