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

Questo lavoro è stato sostenuto dal finanziamento di avvio della Scuola di Ingegneria, Virginia Commonwealth University e alcuni dei dispositivi elettronici sono stati preparati presso le strutture di microfabbricazione della Virginia Wright Microelectronics Center. Riconosciamo i ricercatori che hanno fatto contributi per il dispositivo e dati clinici (figure 3 e 5 in questo articolo), acquistato dal articolo pubblicato 10. W.-HY grazie Yoshiaki Hattori per il, software di registrazione dati su misura.

Gli esperimenti per la fabbricazione del dispositivo, la laminazione della pelle, e la caratterizzazione riportati nelle figure 1, 2, e 4 coinvolti due volontari, tutte eseguite nel nanoingegneria Laboratorio Bio-interfacciato alla Virginia Commonwealth University (VCU), Richmond, VA, USA. Questo studio è stato approvato dal VCU Institutional Review Board (numero di protocollo: HM20001454) e ha seguito le linee di ricerca della VCU umano di ricerca. I dati del dispositivo e clinici illustrati nelle figure 3 e 5 sono stati acquisiti da questo articolo pubblicato 10 dove sono stati condotti gli esperimenti su pazienti con il protocollo (numero: STU69718) approvato dal Institutional Review Board, Northwestern University, Chicago, IL, USA. Fabrication 1. Dispositivo NOTA: La figura 2 presenta illustrazioni schematiche per l&#39;intero processo di fabbricazione. <ol><li> Preparare un substrato di supporto<ol><li> Tagliare un bare 3 in silicio (Si) wafer nella dimensione desiderata dell&#39;elettronica utilizzando una lama diamantata. NOTA: Circa la metà di Si wafer dà una dimensione ideale per il dispositivo ferita. </li><li> Sgrassare Si cialda con acetone e alcool isopropilico (IPA). Lavare il wafer con acqua deionizzata (DI) e poi asciugare con azoto e disidratare su una piastra riscaldante a 110 ° C per 3 min. </li><li> Preparare 11 g di polidimetilsilossano (PDMS) miscela con rapporto 10: 1 volume di base e induritore e degassare la miscela in una camera a vuoto per un&#39;ora. NOTA: PDMS viene utilizzato per un recupero modello asciutto e trasferire la stampa dopo la microfabbricazione, che è preferibile alla chimica umida (acetone) approccio sede dallo studio precedente 7. </li><li> Spin coat 5 g di soluzione di PDMS mista su wafer a 3.000 rpm per 1 min e curare completamente su una piastra riscaldante a 150 ° C per 30 min. </li></ol></li><li> Materiali di deposito e di pattern elettronici <ol><li> Trattare il PDMS-cwafer oated con ultravioletti (UV) / ozono utilizzando una lampada UV (8,9 mW / cm 2) per 3 min a rendere la superficie idrofila. NOTA: La superficie idrofila offre rivestimento uniforme di strati supplementari sulle PDMS. </li><li> Poliimmide Spincoat (PI; 2 ml) sulle PDMS rivestite wafer, pipettando, a 4.000 rpm per 1 min per formare uno strato di 1,2 micron di spessore, pre-cuocere su una piastra riscaldante a 150 ° C per 5 min, e post- cuocere in forno a 250 ° C per 2 ore. </li><li> Deposito di cromo (Cr) per formare uno strato di 20 nm di spessore e poi depositare in rame (Cu) per formare uno strato di 3 micron di spessore mediante fascio elettronico (e-beam) di evaporazione (pressione di base: ~ 1 × 10 -7 Torr , pressione di deposizione: ~ 1 × 10 -6 Torr, velocità di deposizione: 1-5 Å / s). Monitorare lo spessore del film dall&#39;interfaccia regolatore deposizione integrato nell&#39;evaporatore. NOTA: Lo spesso strato di Cu fornisce sufficienti livelli di conducibilità elettrica sulle resistenze microscala del dispositivo e sottile strato di Crviene utilizzato per promuovere l&#39;adesione tra PI e Cu. </li><li> Spincoat un fotoresist (2 ml) con tre gradini 900 rpm per 10 sec, 1.100 rpm per 60 sec, e 4.000 rpm per 20 sec e poi curare su una piastra riscaldante a 75 ° C per 30 min. NOTA: Le fasi successive sopra descritte sono stati usati per depositare una spessa (&gt; 10 micron) fotoresist. </li><li> Allineate Cu elettronici modelli (sensori; frattale &#39;Peano&#39; con 35 micron di larghezza e interconnessioni; disegno a griglia serpentina aperto con 50 micron di larghezza) al centro del Si wafer utilizzando un allineatore UV (potenza: 10 mW / sec) con il tempo di esposizione 25 s. NOTA: Le strutture frattali sono utilizzati per fornire elasticità meccanica superiore, rispetto al solo serpeggianti caratteristiche 14. </li><li> Sviluppare il photoresist in uno sviluppatore di base diluito (rapporto 1: 2 di sviluppatore e acqua deionizzata) per un minuto, risciacquare con acqua deionizzata e asciugare con azoto. Controllare i modelli frattali (Cu e interconnessioni) utilizzando un microscopo di confermare la dimensione del tratto e trovare qualsiasi difetto da particolato. NOTA: Se ci sono difetti indesiderati, quindi rimuovere photoresist sciacquando con acqua acetone / IPA / DI. Dopo l&#39;asciugatura con azoto, ripetere i passaggi da 1.2.4 a 1.2.6. </li><li> Etch strato Cu sulla Si wafer immergendo in un agente di attacco chimico umido per ~ 6 min (10 ml; miscela di persolfato di ammonio e acqua in rapporto 1: 4; etch velocità di 8 nm / sec in 40 ° C), risciacquo con acqua deionizzata e asciugare con azoto. Controllare i modelli usando un microscopio per eventuali modelli over-incise. NOTA: Se i modelli sono sovra-incisi, può causare spigoli indesiderati di caratteristiche, che potrebbero portare a fratture meccanico durante la movimentazione del dispositivo e il processo di lavaggio. I risultati della prova precedenti hanno mostrato che più del ~ 20% over-incisione dei modelli originali causato i problemi di cui sopra. </li><li> Etch lo strato di Cr con ioni reattivi (RIE; pressione: 300 mTorr, potenza: 200 W, CF 4 gas: 5 sccm, O 2 gas: 10 sccm) per 5 min. Controllare i modelli. NOTA: per l&#39;attacco dello strato di Cr, il processo RIE è preferibile bagnare attacco chimico che provoca reazione sfavorevole con lo strato di Cu. </li><li> Rimuovere il fotoresist rimaste sulle strati metallici immergendo il wafer in acetone (10 ml), IPA (10 ml) e acqua deionizzata (20 ml), rispettivamente. Quindi, asciugare con azoto. </li><li> PI Spincoat (2 ml) sul wafer metallo depositato, pipettando, a 4000 rpm per 1 min per formare uno strato di 1,2 micron di spessore, pre-cuocere su una piastra riscaldante a 150 ° C per 5 min, e post-bake a 250 ° C per 2 ore. </li><li> Spincoat un fotoresist (2 ml) con tre gradini 900 rpm per 10 sec, 1.100 rpm per 60 sec, e 4.000 rpm per 20 sec e poi curare su una piastra riscaldante a 75 ° C per 30 min. </li><li> Allineare i modelli PI per incapsulare il elettronica Cu (sensori; frattale &#39;Peano&#39; con 35 micron di larghezza e interconnessioni; disegno della maglia serpentina aperto con 250micron di larghezza) con i frattali e interconnessioni predefiniti Cu utilizzando un assetto UV (potenza: 10 mW / sec) con il tempo di esposizione 25 sec. </li><li> Sviluppare il photoresist con uno sviluppatore diluito (rapporto 1: 2 di sviluppatore e acqua deionizzata) per un minuto, risciacquare con acqua deionizzata e asciugare con azoto. Controllare i modelli usando un microscopio per confermare la dimensione del tratto e trovare qualsiasi difetto da particolato. NOTA: Se ci sono difetti indesiderati, quindi rimuovere photoresist sciacquando con acqua acetone / IPA / DI. Dopo l&#39;asciugatura con azoto, ripetere i passaggi da 1.2.10 a 1.2.13. </li><li> Etch lo strato PI con RIE (pressione: 170 mTorr, potenza: 150 W, O 2 gas: 20 sccm) per 25 minuti. Controllare i modelli. </li><li> Rimuovere il fotoresist rimaste immergendo il wafer in acetone (10 ml), IPA (10 ml) e acqua deionizzata (20 ml), rispettivamente. Quindi, asciugare con azoto. </li></ol></li><li> Preparare una membrana elastomerica <ol><li> Preparare un 10 g di incapsulare miscela in silicone (1:1 rapporto di volume di base e induritore) e aggiungere un inchiostro nero 15 con rapporto uno a uno volume, che è di facilitare misurazioni di controllo della variazione di temperatura sulla pelle con una telecamera a infrarossi. NOTA: Il silicone utilizzato (chiaro gomma incapsulante) fornisce caratteristiche uniche di bassa viscosità, chiarezza ottica, e l&#39;isolamento elettrico / protezione al dispositivo 16. </li><li> Spincoat 8 g della miscela in una capsula di Petri a 150 rpm per 1 min per formare una spessa membrana elastomerica 500 micron e di indurimento a temperatura ambiente per O / N. NOTA: Il materiale deve essere posto su una superficie piana per spessore uniforme. </li><li> Tagliare la membrana nella dimensione desiderata di 70 mm x 30 mm utilizzando una lametta affilata e staccarlo delicatamente dalla capsula di Petri. </li></ol></li><li> Recuperare e trasferire elettronica <ol><li> Tagliare un nastro solubile in acqua (25 mm x 80 mm) e laminare delicatamente sui modelli elettronici fabbricati e metterli su una piastra a 130 ° Cper 3 min. NOTA: elevazione Temperatura espande lo strato PDMS sul wafer di Si di aiutare dissociazione dei modelli elettronici dalla superficie. </li><li> Staccare il nastro rapidamente dalla PDMS / Si wafer per recuperare i modelli elettronici. </li><li> Deposito a 20 nm di spessore Cr (per adesione) seguito da un nm biossido di silicio di spessore 50 (SiO 2) sui modelli recuperati tramite e-beam evaporazione. </li><li> Trattare UV / ozono utilizzando lampada UV (365 nm, 8,9 mW / cm 2) sulla membrana di silicone mirato per 2 minuti per attivare la superficie. </li><li> Trasferire i pattern alla membrana siliconica ponendo i modelli recuperati sul nastro nella posizione desiderata e uniformemente aggiungendo la pressione dal lato superiore dei modelli fino al substrato. Applicare acqua per sciogliere il nastro per 5 min. NOTA: Il processo descritto di materiali trasferimento è facilitato dal legame covalente (Si-O-Si) tra il biossido di silicio depositato ed il substrato di silicone-UV attivata 17 </sup&gt;. </li><li> Staccare il nastro, sciacquare con acqua deionizzata e asciugare su una piastra a 90 ° C per 1 min. </li></ol></li><li> Incapsulare il dispositivo utilizzando un membrana di silicone <ol><li> Preparare un 10 g di incapsulare miscela silicone (rapporto 1: 1 volume di base e induritore). </li><li> Coprire le piazzole di contatto del cavo con un pezzo PDMS rettangolare (22 × 6 × 1 mm 3) da van der Waals legame con la membrana di silicone fondo, per evitare silicone rivestimento delle pastiglie. </li><li> Spincoat il 5 g di miscela di silicone a 4.000 rpm per 1 min per formare uno strato di spessore 5 micron sull&#39;elettronica trasferiti e quindi polimerizzare a RT per O / N. </li></ol></li><li> Collegare un cavo a nastro flessibile per l&#39;acquisizione dei dati <ol><li> Applicare flusso di acciaio liquido (0,5 ml), pipettando, sul pad connettore per 3 secondi per fare superficie pulita. </li><li> Bond A, cavo a nastro flessibile sottile sui punti di contatto con pressione ad alta temperatura (&gt; 60 ° C). Un tipico straightene capelliR offre maneggevolezza e incollaggio. NOTA: Il cavo micro-film è preferibile alla saldatura convenzionale hard-wire per evitare qualsiasi frattura meccanica delle membrane metalliche trasferiti su un silicone. </li><li> Controllare il collegamento elettrico con un multimetro digitale. Il valore di resistenza è prevista meno di 1 Ohm tra il pad sensore con una estremità e l&#39;altra estremità del cavo pellicola (distanza: ~ 1 cm di distanza). </li><li> Legare l&#39;altra estremità del cavo a nastro un circuito stampato personalizzato con la stessa strategia descritta nel passaggio 1.6.2. </li><li> Controllare il collegamento elettrico con un multimetro digitale. </li><li> Collegare il dispositivo con l&#39;hardware di acquisizione dati saldando fili convenzionali sul PCB. </li></ol></li></ol> 2. sperimentazione clinica <ol><li> Pulire il dispositivo utilizzando una soluzione disinfettante <ol><li> Preparare 205 g di una soluzione disinfettante diluita (40: 1 rapporto di volume di acqua e soluzione). </li><li> Spruzzare lasoluzione (10 g) sul dispositivo e ammollo per 10 min. NOTA: Il pulitore disinfettante diluita può essere conservata a temperatura ambiente. </li><li> Risciacquare con acqua per tre volte e asciugare con tessuti puliti. </li></ol></li><li> Impostare una serie di attrezzature per il test del dispositivo <ol><li> Preparare e collegare un amplificatore lock-in con un generatore di corrente, un multiplexer, e il software personalizzato installato su un computer portatile per la registrazione dei dati. </li><li> Posizionare una telecamera a infrarossi su un treppiede e concentrarsi su un oggetto di destinazione per la termografia come riferimento. </li><li> Impostare i parametri di sistema di un amplificatore lock-in per misurare la conducibilità termica (frequenza: 1 e 3 Hz; costante di tempo: 3 e 1 secondo; Sensibilità: 1 mV; riserva dinamica: alta riserva) e della temperatura (frequenza: 997 Hz, il tempo costante: 300 msec; sensibilità: 2 mV; riserva dinamica: a basso rumore) con l&#39;applicazione corrente costante (2 mA). </li><li> Collegare due dispositivi ferita, preparato da microfabbricazione e trasferimento di stampa e montato sulla ferita esiti controlaterale, al multiplexer destra prima di registrare i dati di un paziente. </li></ol></li><li> Registrare la temperatura e conducibilità termica NOTA: Il software di acquisizione dei dati è su ordine, in grado di controllare a distanza il amplificatore lock-in per il monitoraggio dei dati in tempo reale e risparmio. Nella misura di temperatura, ciascun punto di dati viene misurata ogni 300 msec per 20 sec. L&#39;insieme di dati per i primi 10 secondi e dopo 10 sec vengono utilizzati per calcolare il valore medio e la deviazione standard di temperatura, rispettivamente. I dati registrati vengono memorizzati come file valori separati da virgole, che viene utilizzato per tracciare un grafico di confronto con i dati di termografia infrarossa. Nella misura di conducibilità termica, i segnali 3Ω vengono letti direttamente dalla schermata hardware (amplificatore), che viene quindi utilizzato per calcolare la conduttività termica analiticamente. <ol><li> Strofinare delicatamente i siti di applicazione del dispositivo sulla pelle con alcool antisettico salviette 10. </li><li> 2.3.2) Laminato due dispositivi delle sedi cutanee desiderate premendo delicatamente il dispositivo alla pelle con le dita per facilitare l&#39;incollaggio morbido: uno sul sito della ferita chirurgica e l&#39;altra sulla posizione controlaterale come riferimento. </li><li> Misurare la tensione elettrica (3Ω), correlata alla conducibilità termica, del dispositivo avviando l&#39;acquisizione dei dati. </li><li> Valutare i dati ottenuti per verificare il contatto del dispositivo conforme alla pelle; Valore anormale (&lt;0.1 W / mK) mostra una cattiva contatto del dispositivo. </li><li> Misurare la resistenza elettrica per determinare la distribuzione della temperatura e registrare i dati tramite il software personalizzato. </li><li> Prendere immagini ottiche e IR dei due dispositivi sulla pelle. </li><li> Confrontare i valori di temperatura dalle immagini a infrarossi con i dati registrati dal dispositivo ferita (2.3.5). Aggiungi entrambi i valori per separare le colonne in un foglio di calcolo personalizzato. </li></ol></li><li> Analizzare i dati registrati <ol><li> Esportare i dati registrati altemplate personalizzato per calcolare automaticamente la temperatura e la conducibilità termica da una matrice di sensori nel dispositivo. </li><li> Tracciare i dati (temperatura e conducibilità termica secondo la posizione del sensore su una scala temporale diverso) per confronto nel corso di un mese (quattro set di dati al giorno 1, 3, 15, e 30). </li><li> Analizzare i dati confrontando una serie di dati di temperatura e conducibilità termica in funzione del tempo; I valori con improvviso innalzamento o cadere dire il cambiamento di fase di guarigione della ferita e / o anormalità inaspettato su siti ferite. </li></ol></li></ol>

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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...

In studio clinico e della ricerca biomedica, il monitoraggio di guarigione della ferita si è concentrata su un metodo invasivo che si basa sulla valutazione istologica del tessuto variazione morfologica nelle ferite 1,2. Recentemente, rapidi progressi nelle tecnologie elettroniche consentono lo sviluppo di immagini e strumenti di analisi di alta precisione in grado di ispezionare visivamente il processo di guarigione delle ferite attraverso l&#39;imaging digitale 3,4 o la microscopia confocale a scansione e spettroscopia 4,5. Tuttavia, tali approcci di imaging richiedono costi elevati, strumenti ottici complessi e operazioni, e, soprattutto, i pazienti devono essere immobilizzata durante la prova. Pertanto, esiste la necessità di nuovi dispositivi e sistemi che sono quantitative, non invasivo, facile da usare, poco costoso, e multifunzionale per offrire una gestione più accurata della ferita. Qui, si introduce un sistema elettronico simil-pelle, che fornisce precise e in tempo reale la mappatura della temperatura e termiche conductivity e offre un livello preciso di riscaldamento nei siti della ferita via conformazionale laminazione del dispositivo non invasivo. Questo dispositivo presenta una classe di tecnologie, impianti a pelle epidermica elettronici che sono progettati per corrispondere alle proprietà meccaniche e dei materiali (spessore totale, rigidezza flessionale, moduli efficaci, e la densità di massa) dell&#39;epidermide 6-9. Il dispositivo è stato progettato in un,, impermeabile pelle-amichevole biocompatibile, e la forma riutilizzabile che può essere lavato e disinfettato per le applicazioni cliniche sui pazienti 10. Il dispositivo elettronico conforme montato vicino tessuti ferita cattura fase di infiammazione (uno dei processo di guarigione delle ferite), causata da un aumento del flusso sanguigno e reazioni enzimatiche alla ferita 11,12, attraverso la registrazione quantitativa di temperatura 8 e conducibilità termica 13, correlato alla idratazione . Studi sperimentali e computazionali determinano un design ottimale meccanica per alloggiomangiato movimenti naturali e applicate ceppi senza frattura meccanica e catturare fisica di base di stretching meccanica dell&#39;elettronica pelle-like che laminati conformally sulla superficie della pelle, che offre acquisizione di segnali ad alta fedeltà. I protocolli descritti in questo articolo presentano i metodi di microfabbricazione per sistemi elettronici simil-pelle, test di preparazione compresa la pulizia del dispositivo, l&#39;installazione apparecchi in ambito clinico, e applicazioni cliniche per il monitoraggio quantitativo della temperatura e conducibilità termica sulle ferite cutanee.

<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.

Figura 1 presenta una panoramica delle caratteristiche del conformazionale, sistema elettronico skin-like, progettato per quantitativa, gestione cutanea avvolto su pazienti. Il dispositivo elettronico multifunzionale costituito da microscala strutture frattali 3,14 e serpentino filamentosa traccia 9,17 su una membrana elastomerica sottile che offre un&#39;eccezionale elasticità meccanica e piegabilità. Il dispositivo compatibile che è completamente racchiuso da strati di silicon...

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.

Fabbricazione e la caratterizzazione di un Conformal pelle simile sistema elettronico di gestione quantitativa, cutanea Ferita

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

Universidad de Cartagena UDEC

Research

JoVE Journal

Bioengineering

8.8K Views.  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. 

Video: 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.

Hollow microago-based sensore per Multiplexed transdermico elettrochimica Sensing

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

Ricerca

Bioingegneria

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.

Colmare il Bio-Electronic Interface con Biofabrication

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.

Una pelle piena Difetto modello per valutare Vascolarizzazione di Biomateriali<em&gt; In Vivo</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.

Generazione di una tridimensionale a tutto spessore della pelle Equivalent e Automated Ferimento

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.

Un metodo semplice e scalabile di fabbricazione per dispositivi elettronici organici sui tessili

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.

Modello di ferita umana ex vivo e approccio di colorazione a montaggio intero per valutare con precisione la riparazione della pelle

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

Biologia dello sviluppo

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.

Generazione di equivalenti di pelle umana vascolarizzata auto-assemblati

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.

Generazione di un modello skin-on-a-chip tridimensionale semplificato in una piattaforma microfluidica microlavorazione

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.

Elettrodi indossabili conformabili: dalla fabbricazione alla valutazione elettrofisiologica

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.

Sviluppo di un modello da banco per la valutazione della compatibilità dei materiali per la medicazione delle ferite con i sistemi di terapia delle ferite a pressione negativa

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