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Instrumentação para a aplicação não invasiva de medicação usando sonoforese e iontoforese

Abstract

Trabalho de Projeto do Mestrado Integrado em Engenharia Biomédica apresentado à Faculdade de Ciências e Tecnologia

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Instrumentação para a aplicação não invasiva de medicação usando sonoforese e iontoforese

Author: Amado, Catarina Filipa Honrado
Year: 2019
Source: https://estudogeral.uc.pt/bitstream/10316/83249/1/Tese%20final%20Catarina%20Amado.pdf
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Catarina Amado
Instrumen ta¸ c ˜ ao para a aplica¸ c ˜ ao n ˜ ao
in v asiv a de medica¸ c ˜ ao usando
sonoforese e ion toforese
Disserta¸ c˜ ao apresen tada ` a Univ ersidade de Coim bra
para cumprimen to dos requisitos necess´ arios ` a
obten¸ c˜ ao do grau de Meste em Engenharia Biom ´ edica
Orien tadores:
Eng. Nuno Figueiredo (Exatronic, Engenharia Electr´ onica, Lda.)
Prof. Jo˜ ao Cardoso (Univ ersidade de Coim bra)
Coim bra, 2017

Este trabalho foi desen v olvido em colab ora¸ c˜ ao com:
Exatronic, Engenharia Electr´ onica, Lda
Av eiro, P ortugal
Departamen to de F ´ ısica, Univ ersidade de Coim bra
Coim bra, P ortugal

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* Base CSS for pdf2htmlEX
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* https://github.com/pdf2htmlEX/pdf2htmlEX/blob/master/share/LICENSE
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Esta c´ opia da tese ´ e fornecida na condi¸ c˜ ao de que quem a consulta reconhece que os
direitos de autor s˜ ao p erten¸ ca do autor da tese e que nenh uma cita¸ c˜ ao ou informa¸ c˜ ao
obtida a partir dela p o de ser publicada sem a refer ˆ encia apropriada.
This cop y of the thesis has b een supplied on condition that an y one who consults
it is understo o d to recognize that its cop yrigh t rests with its author and that no
quotation from the thesis and no information deriv ed from it ma y b e published
without prop er ac kno wledgemen t.

A o Dep artamento de F ´ ısic a
`
A Ci ˆ encia

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display:block;
}
.bf_c00002 { /* images that occupies the whole page */
position:absolute;
border:0;
margin:0;
top:0;
bottom:0;
width:100%;
height:100%;
-ms-user-select:none;
-moz-user-select:none;
-webkit-user-select:none;
user-select:none;
}
.bi_c00002 { /* images that cover only a part of the page */
position:absolute;
border:0;
margin:0;
-ms-user-select:none;
-moz-user-select:none;
-webkit-user-select:none;
user-select:none;
}
@media print {
.pf_c00002 {
margin:0;
box-shadow:none;
page-break-after:always;
page-break-inside:avoid;
}
@-moz-document url-prefix() {
/* fix page truncation for FireFox */
.pf_c00002 {
overflow:visible;
border:1px solid #FFFFFF;
}
.pc_c00002 {overflow:visible;}
}
}
.c_c00002 { /* clip box */
position:absolute;
border:0;
padding:0;
margin:0;
overflow:hidden;
display:block;
}
.t_c00002 { /* text line */
position:absolute;
white-space:pre;
font-size:1px;
transform-origin:0% 100%;
-ms-transform-origin:0% 100%;
-webkit-transform-origin:0% 100%;
unicode-bidi:bidi-override;/* For rtl languages, e.g. Hebrew, we don't want the default Unicode behaviour */
-moz-font-feature-settings:"liga" 0;/* We don't want Firefox to recognize ligatures */
}
.t_c00002:after { /* webkit #35443 */
content: '';
}
.t_c00002:before { /* Workaround Blink(up to 41)/Webkit bug of word-spacing with leading spaces (chromium #404444 and pdf2htmlEX #412) */
content: '';
display: inline-block;
}
.t_c00002 span { /* text blocks within a line */
/* Blink(up to 41)/Webkit have bug with negative word-spacing and inline-block (pdf2htmlEX #416), so keep normal span inline. */
position:relative;
unicode-bidi:bidi-override; /* For rtl languages, e.g. Hebrew, we don't want the default Unicode behaviour */
}
.__c00002 { /* text shift */
/* Blink(up to 41)/Webkit have bug with inline element, continuous spaces and word-spacing. Workaround by inline-block. */
display: inline-block;
color: transparent;
z-index: -1;
}
/* selection background should not be opaque, for fallback mode */
::selection{
background: rgba(127,255,255,0.4);
}
::-moz-selection{
background: rgba(127,255,255,0.4);
}
.pi_c00002 { /* info for Javascript */
display:none;
}
.l_c00002 { /* annotation links */
}
/* transparent color - WebKit */
.d_c00002 { /* css drawing */
position:absolute;
transform-origin:0% 100%;
-ms-transform-origin:0% 100%;
-webkit-transform-origin:0% 100%;
}
/* for the forms */
.it_c00002 {
border: none;
background-color: rgba(255, 255, 255, 0.0);
}

.ir_c00002:hover {
cursor: pointer;
}

/* Base CSS END */

/* vim: set shiftwidth=2 tabstop=2 autoindent cindent expandtab filetype=css: */
/*!
* Fancy styles for pdf2htmlEX
* Copyright 2012,2013 Lu Wang
* https://github.com/pdf2htmlEX/pdf2htmlEX/blob/master/share/LICENSE
*/
@keyframes fadein { from { opacity:0;} to { opacity:1;} }
@-webkit-keyframes fadein { from { opacity:0;} to { opacity:1;} }
@keyframes swing {
0% { transform: rotate(0deg); }
10% { transform: rotate(0deg); }
90% { transform: rotate(720deg); }
100%{ transform: rotate(720deg); }
}
@-webkit-keyframes swing {
0% { -webkit-transform: rotate(0deg); }
10% { -webkit-transform: rotate(0deg); }
90% { -webkit-transform: rotate(720deg); }
100%{ -webkit-transform: rotate(720deg); }
}
@media screen {
#sidebar {
background-color:#2f3236;
/* modified from http://philbit.com/svgpatterns/#crossstripes */
background-image:url("data:image/svg+xml;base64,PHN2ZyB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciIHdpZHRoPSI0IiBoZWlnaHQ9IjQiPgo8cmVjdCB3aWR0aD0iNCIgaGVpZ2h0PSI0IiBmaWxsPSIjNDAzYzNmIj48L3JlY3Q+CjxwYXRoIGQ9Ik0wIDBMNCA0Wk00IDBMMCA0WiIgc3Ryb2tlLXdpZHRoPSIxIiBzdHJva2U9IiMxZTI5MmQiPjwvcGF0aD4KPC9zdmc+");
}
#outline {
font-family:Georgia,Times,"Times New Roman",serif;
font-size:13px;
margin:2em 1em;
}
#outline ul {
padding:0;
}
#outline li {
list-style-type:none;
margin:1em 0;
}
#outline li > ul {
margin-left: 1em;
}
#outline a,
#outline a:visited,
#outline a:hover,
#outline a:active {
line-height:1.2;
color:#e8e8e8;
text-overflow:ellipsis;
white-space:nowrap;
text-decoration:none;
display:block;
overflow:hidden;
outline:0;
}
#outline a:hover {
color:rgb(0,204,255);
}
#page-container {
background-color:#9e9e9e;
/* http://philbit.com/svgpatterns/#thinstripes */
background-image: url("data:image/svg+xml;base64,PHN2ZyB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciIHdpZHRoPSI1IiBoZWlnaHQ9IjUiPgo8cmVjdCB3aWR0aD0iNSIgaGVpZ2h0PSI1IiBmaWxsPSIjOWU5ZTllIj48L3JlY3Q+CjxwYXRoIGQ9Ik0wIDVMNSAwWk02IDRMNCA2Wk0tMSAxTDEgLTFaIiBzdHJva2U9IiM4ODgiIHN0cm9rZS13aWR0aD0iMSI+PC9wYXRoPgo8L3N2Zz4=");
-webkit-transition:left 500ms;
transition:left 500ms;
}
.pf_c00002 {
margin: 13px auto;
box-shadow: 1px 1px 3px 1px #333;
/* Needed by IE to make box-shadow works * https://developer.mozilla.org/en-US/docs/Web/CSS/box-shadow */
border-collapse: separate;
}
.pc_c00002.opened { /* used by pdf2htmlEX.js, to show/hide pages */
-webkit-animation: fadein 100ms;
animation: fadein 100ms;
}
.loading-indicator_c00002.active {
/*
* use 0.01s instead of 0s,
* since YUI Compressor will change 0s to 0,
* which is not recognized by Firefox
*/
-webkit-animation: swing 1.5s ease-in-out 0.01s infinite alternate none;
animation: swing 1.5s ease-in-out 0.01s infinite alternate none;
}
.checked_c00002 {
background: no-repeat url(data:image/png;base64,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);
}
}
/* Fancy CSS END */

.ff0_c00002{font-family:sans-serif;visibility:hidden;}
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”Life is pr etty simple: Y ou do some stuff. Most fails. Some works. Y ou do mor e of
what works. If it works big, others quickly c opy it. Then you do something else.
The trick is the doing something else. ”
Leonardo da Vinci

Agradecimen tos
´
E o momen to de transi¸ c˜ ao de mais uma etapa que s´ o foi p oss ´ ıv el ao lado de p es-
soas dedicadas e talen tosas. Come¸ co agradecendo a elas o seu con tributo no meu
desen v olvimen to.
Obrigada a to da a estrutura do curso de Engenharia Biom ´ edica da UC, em esp ecial ` a
com unidade do Departamen to de F ´ ısica, p elo am bien te familiar e en v olv en te que s´ o
´ e p oss ´ ıv el gra¸ cas ` a dedica¸ c˜ ao fenomenal destes funcion´ arios e professores. Obrigada
ao Professor Jo˜ ao Cardoso que pron tamen te se dedicou a orien tar este pro jeto e que,
com a sua vis˜ ao cr ´ ıtica e acessibilidade, a judou a tornar tudo p oss ´ ıv el.
Um grande obrigada ` a Exatronic, em esp ecial ` a equipa talen tosa do C&D. Obrigada
ao Man uel Loureiro p elas in terv en¸ c˜ oes construtiv as e to do o ap oio t ´ ecnico. Obrigada
ao Nuno Figueiredo p ela acessibilidade e ap oio neste pro jeto. Obrigada ao Deniz
p ela vis˜ ao e exp eri ˆ encia partilhada. Obrigada ao Marco, ao ´
Oscar, ao P edro do
Mar, ao Marques e ` a Maria Jo˜ ao. O meu obrigada gigan te p ela transfer ˆ encia de
conhecimen tos de engenharia.
Obrigada aos meus colegas, ` as minhas Meninas e aos A migos . Obrigada ` a jeKno-
wledge e ` a organiza¸ c˜ ao do melhor ENEEB de sempre. Obrigada ao F ado, obrigada
a Coim bra. Gr azie mil le a Mil˜ ao e aos amigos de Erasm us.
O meu ´ ultimo obrigada e o mais longo, p orque ´ e um obrigada p or to das as etapas que
foram a base para esta etapa atual. Agrade¸ co aos amigos da M ˆ eda, p ela viv ˆ encia
forte e p ela presen¸ ca constan te mesmo ao longe, e ao agrupamen to de escuteiros
1340 p elo crescimen to construtiv o. O meu maior obrigada ´ e direcionado ` a minha
fam ´ ılia. Obrigada ao meu pai, ` a minha m˜ ae, ` a irm˜ a P atr ´ ıcia e ao irm˜ ao P edro.
Obrigada p elo exemplo, p elo v osso en v olvimen to e sup orte em cada no v o desafio, p ela
dedica¸ c˜ ao e compreens˜ ao. Obrigada p or me mostrarem que o trabalho, a h umildade
e a con viv ˆ encia s˜ ao uma ferramen ta imprescind ´ ıv el em to das as etapas.
Um Obrigada gigan te a to dos v´ os.

Abstract
The con v en tional routes of medication deliv ery ha v e man y inheren t limitations whic h
can b e o v ercome b y adv anced drug deliv ery metho ds suc h as transdermal drug de-
liv ery . Ho w ev er, transdermal deliv ery is curren tly restricted to appro ximately only
17 drug molecules, appro v ed b y the US F o o d and Drug Administration (FD A), [1].
This limited n um b er is due to the c hallenge of meeting a p oten t pharmacological
activit y and suitable ph ysico c hemical prop erties to enable skin p enetration.
Ultrasound is a form of energy that in teracts directly with the skin, promoting
sev eral bio effects within a wide frequency range of the acoustic w a v e. The pro cess
b y whic h ultrasound is applied to increase the p ermeabilit y of the skin and promote
molecular transp ort is termed sonophoresis.
A researc h on transdermal transp ort has led to the study of other forms of molecular
transp ort. The electric curren t has the abilit y to in teract either with the c harge-
carrying molecules or with the o wn structure of the skin, dep ending on the applied
v oltage profile. Molecular transp ort enhanced b y the electric curren t is referred as
ion tophoresis.
Additionally to the initial goal of transmitting ultrasound energy , the dev elopmen t
of a system to p erform ion tophoresis is joined to the pro ject. The actual goal is
the dev elopmen t of a medical device that p erforms sonophoresis and ion tophoresis,
through the transmission of b oth lo w and high frequency ultrasound b eams and an
electric curren t.
The tests p erformed on the dev elop ed system sho w a functional and satisfactory
b eha vior of the ion tophoresis system, but the sonophoresis system pro v es to b e
ineffectiv e for driving ultrasound transducers. A t this p oin t, a second approac h
based on a crystal oscillator circuit design is dev elop ed. This approac h w as only
dev elop ed for the transmission of high frequency ultrasound and pro v es to b e efficien t
in the pro duction of acoustic energy .

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display:block;
}
.bf_c00003 { /* images that occupies the whole page */
position:absolute;
border:0;
margin:0;
top:0;
bottom:0;
width:100%;
height:100%;
-ms-user-select:none;
-moz-user-select:none;
-webkit-user-select:none;
user-select:none;
}
.bi_c00003 { /* images that cover only a part of the page */
position:absolute;
border:0;
margin:0;
-ms-user-select:none;
-moz-user-select:none;
-webkit-user-select:none;
user-select:none;
}
@media print {
.pf_c00003 {
margin:0;
box-shadow:none;
page-break-after:always;
page-break-inside:avoid;
}
@-moz-document url-prefix() {
/* fix page truncation for FireFox */
.pf_c00003 {
overflow:visible;
border:1px solid #FFFFFF;
}
.pc_c00003 {overflow:visible;}
}
}
.c_c00003 { /* clip box */
position:absolute;
border:0;
padding:0;
margin:0;
overflow:hidden;
display:block;
}
.t_c00003 { /* text line */
position:absolute;
white-space:pre;
font-size:1px;
transform-origin:0% 100%;
-ms-transform-origin:0% 100%;
-webkit-transform-origin:0% 100%;
unicode-bidi:bidi-override;/* For rtl languages, e.g. Hebrew, we don't want the default Unicode behaviour */
-moz-font-feature-settings:"liga" 0;/* We don't want Firefox to recognize ligatures */
}
.t_c00003:after { /* webkit #35443 */
content: '';
}
.t_c00003:before { /* Workaround Blink(up to 41)/Webkit bug of word-spacing with leading spaces (chromium #404444 and pdf2htmlEX #412) */
content: '';
display: inline-block;
}
.t_c00003 span { /* text blocks within a line */
/* Blink(up to 41)/Webkit have bug with negative word-spacing and inline-block (pdf2htmlEX #416), so keep normal span inline. */
position:relative;
unicode-bidi:bidi-override; /* For rtl languages, e.g. Hebrew, we don't want the default Unicode behaviour */
}
.__c00003 { /* text shift */
/* Blink(up to 41)/Webkit have bug with inline element, continuous spaces and word-spacing. Workaround by inline-block. */
display: inline-block;
color: transparent;
z-index: -1;
}
/* selection background should not be opaque, for fallback mode */
::selection{
background: rgba(127,255,255,0.4);
}
::-moz-selection{
background: rgba(127,255,255,0.4);
}
.pi_c00003 { /* info for Javascript */
display:none;
}
.l_c00003 { /* annotation links */
}
/* transparent color - WebKit */
.d_c00003 { /* css drawing */
position:absolute;
transform-origin:0% 100%;
-ms-transform-origin:0% 100%;
-webkit-transform-origin:0% 100%;
}
/* for the forms */
.it_c00003 {
border: none;
background-color: rgba(255, 255, 255, 0.0);
}

.ir_c00003:hover {
cursor: pointer;
}

/* Base CSS END */

/* vim: set shiftwidth=2 tabstop=2 autoindent cindent expandtab filetype=css: */
/*!
* Fancy styles for pdf2htmlEX
* Copyright 2012,2013 Lu Wang
* https://github.com/pdf2htmlEX/pdf2htmlEX/blob/master/share/LICENSE
*/
@keyframes fadein { from { opacity:0;} to { opacity:1;} }
@-webkit-keyframes fadein { from { opacity:0;} to { opacity:1;} }
@keyframes swing {
0% { transform: rotate(0deg); }
10% { transform: rotate(0deg); }
90% { transform: rotate(720deg); }
100%{ transform: rotate(720deg); }
}
@-webkit-keyframes swing {
0% { -webkit-transform: rotate(0deg); }
10% { -webkit-transform: rotate(0deg); }
90% { -webkit-transform: rotate(720deg); }
100%{ -webkit-transform: rotate(720deg); }
}
@media screen {
#sidebar {
background-color:#2f3236;
/* modified from http://philbit.com/svgpatterns/#crossstripes */
background-image:url("data:image/svg+xml;base64,PHN2ZyB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciIHdpZHRoPSI0IiBoZWlnaHQ9IjQiPgo8cmVjdCB3aWR0aD0iNCIgaGVpZ2h0PSI0IiBmaWxsPSIjNDAzYzNmIj48L3JlY3Q+CjxwYXRoIGQ9Ik0wIDBMNCA0Wk00IDBMMCA0WiIgc3Ryb2tlLXdpZHRoPSIxIiBzdHJva2U9IiMxZTI5MmQiPjwvcGF0aD4KPC9zdmc+");
}
#outline {
font-family:Georgia,Times,"Times New Roman",serif;
font-size:13px;
margin:2em 1em;
}
#outline ul {
padding:0;
}
#outline li {
list-style-type:none;
margin:1em 0;
}
#outline li > ul {
margin-left: 1em;
}
#outline a,
#outline a:visited,
#outline a:hover,
#outline a:active {
line-height:1.2;
color:#e8e8e8;
text-overflow:ellipsis;
white-space:nowrap;
text-decoration:none;
display:block;
overflow:hidden;
outline:0;
}
#outline a:hover {
color:rgb(0,204,255);
}
#page-container {
background-color:#9e9e9e;
/* http://philbit.com/svgpatterns/#thinstripes */
background-image: url("data:image/svg+xml;base64,PHN2ZyB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciIHdpZHRoPSI1IiBoZWlnaHQ9IjUiPgo8cmVjdCB3aWR0aD0iNSIgaGVpZ2h0PSI1IiBmaWxsPSIjOWU5ZTllIj48L3JlY3Q+CjxwYXRoIGQ9Ik0wIDVMNSAwWk02IDRMNCA2Wk0tMSAxTDEgLTFaIiBzdHJva2U9IiM4ODgiIHN0cm9rZS13aWR0aD0iMSI+PC9wYXRoPgo8L3N2Zz4=");
-webkit-transition:left 500ms;
transition:left 500ms;
}
.pf_c00003 {
margin: 13px auto;
box-shadow: 1px 1px 3px 1px #333;
/* Needed by IE to make box-shadow works * https://developer.mozilla.org/en-US/docs/Web/CSS/box-shadow */
border-collapse: separate;
}
.pc_c00003.opened { /* used by pdf2htmlEX.js, to show/hide pages */
-webkit-animation: fadein 100ms;
animation: fadein 100ms;
}
.loading-indicator_c00003.active {
/*
* use 0.01s instead of 0s,
* since YUI Compressor will change 0s to 0,
* which is not recognized by Firefox
*/
-webkit-animation: swing 1.5s ease-in-out 0.01s infinite alternate none;
animation: swing 1.5s ease-in-out 0.01s infinite alternate none;
}
.checked_c00003 {
background: no-repeat url(data:image/png;base64,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);
}
}
/* Fancy CSS END */

.ff0_c00003{font-family:sans-serif;visibility:hidden;}
@font-face{font-family:ff1_c00003;src:url('data:application/font-woff;base64,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Resumo
As vias con v encionais de administra¸ c˜ ao de f´ armaco apresen tam v´ arias limita¸ c˜ oes que
p o dem ser sup eradas atra v ´ es de meto dologias a v an¸ cadas de administra¸ c˜ ao, como o
transp orte de f´ armaco via transd ´ ermica. Con tudo, esta meto dologia est´ a limitada
atualmen te a um n ´ umero m uito restrito de mol ´ eculas de f´ armaco, em resultado
da dificuldade em encon trar o melhor compromisso en tre a p ot ˆ encia da atividade
farmacol´ ogica e as propriedades fisico-qu ´ ımicas da p ele.
Os ultrassons constituem uma forma de energia que in terage diretamen te com a
p ele, promo v endo div ersos bio efeitos pro v enien tes de uma faixa de baixa a elev ada
frequ ˆ encia da onda ac ´ ustica. O pro cesso p elo qual os ultrassons s˜ ao aplicados para
aumen tar a p ermeabilidade da p ele e promo v er o transp orte molecular ´ e denominado
de sonoforese.
A in v estiga¸ c˜ ao aprofundada sobre o transp orte transd ´ ermico conduziu ao estudo de
outras formas ativ as de transp orte. A corren te el ´ etrica tem a capacidade de in teragir
com as mol ´ eculas p ortadoras de carga ou com a pr´ opria estrutura da p ele, dep en-
dendo das caracter ´ ısticas do p otencial aplicado. O transp orte molecular otimizado
p ela corren te el ´ etrica ´ e conhecido p or ion toforese.
Ao ob jetiv o inicial de transmitir energia de ultrassons, ´ e adicionado o desen v olvi-
men to de um sistema para realizar a ion toforese. O ob jetiv o do pro jeto ´ e o desen-
v olvimen to de um disp ositiv o m ´ edico que efetua sonoforese e ion toforese, p or meio
da transmiss˜ ao de ultrassons de baixa e elev ada frequ ˆ encia e de corren te el ´ etrica.
Os testes ao sistema desen v olvido rev elam um comp ortamen to funcional e satis-
fat´ orio do sistema dedicado ` a ion toforese, j´ a o sistema de sonoforese demonstra ser
ineficaz no driving dos transdutores de ultrassom. Neste p on to do pro jeto, ´ e desen-
v olvida uma segunda ab ordagem que tem p or base o design de um circuito oscilador
de cristal. Esta ab ordagem foi ap enas desen v olvida para a transmiss˜ ao de ultrassons
de elev ada frequ ˆ encia e rev ela ser eficien te na pro du¸ c˜ ao da energia ac ´ ustica.

Acr´ onimos
ADC A nalo g-to-Digital Converter
BJT Bip olar Junction T r ansistor
CMRR Common-Mo de R eje ction R atio
CPU Centr al Pr o c essing Unit
CR C Cyclic R e dundancy Che ck
D A C Digital-to-A nalo g Converter
DM Disp ositiv o M ´ edico
DMA Dir e ct Memory A c c ess
EC Estrato C´ orneo
FD A F o o d and Drug A dministr ation
FET Field-effe ct T r ansistor
IEC International Ele ctr ote chnic al Commission
MCU Micr o c ontr ol ler Unit
MOSFET Metal Oxide Semic onductor Field Effe ct T r ansistor
n˜ ao-R TL Regi˜ oes de T ransp orte n˜ ao Lo calizado
OC Output Comp ar e
OMS Organiza¸ c˜ ao Mundial de Sa ´ ude
Op-amp Op er ational amplifier
OSR Over Sampling R atio
PCB Printe d Cir cuit Bo ar d
PLL Phase-L o cke d L o op
xvii

PRP P er ´ ıo do de Rep eti¸ c˜ ao de Pulsos
PWM Pulse-Width Mo dulation
R TL Regi˜ oes de T ransp orte Lo calizado
SBF Sonoforese de Baixa F requ ˆ encia
SFE Sonoforese de F requ ˆ encia Elev ada
SNR Signal-to-noise r atio
TFT T ransp orte de F´ armaco via T ransd ´ ermica
UAR T Universal Asynchr onous R e c eiver/T r ansmitter
UI User Interfac e
USB Universal Serial Bus
UTS Ultrassons
V CO V oltage-Contr ol le d Oscil lator
XAML Extensible Applic ation Markup L anguage
xviii

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* which is not recognized by Firefox
*/
-webkit-animation: swing 1.5s ease-in-out 0.01s infinite alternate none;
animation: swing 1.5s ease-in-out 0.01s infinite alternate none;
}
.checked_c00004 {
background: no-repeat url(data:image/png;base64,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);
}
}
/* Fancy CSS END */

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}

Lista de Figuras
1.1 Ev olu¸ c˜ ao da p ercen tagem de p opula¸ c˜ ao m undial com diab etes no
p er ´ ıo do compreendido en tre 1980 e 2014 [2]. . . . . . . . . . . . . . . 3
1.2 Diagrama de Gan tt para o planeamen to inicial do pro jeto. . . . . . . 6
1.3 Diagrama de Gan tt para o temp o real de desen v olvimen to real pro-
j e t o . .................................... 7
1.4 Log´ otip o da Exatronic. Website : h ttps://www.exatronic.pt . . . . . . 8
2.1 Estrutura da p ele e vias de transp orte p ercutˆ aneo. A: via in trace-
lular; B: via in tercelular; C: canal seb´ aceo; D: via transfolicular; E:
glˆ andulas de suor. Adaptado de [3]. . . . . . . . . . . . . . . . . . . 10
2.2 P osicionamen to do estrato c´ orneo na p ele (` a esquerda) e sua com-
p osi¸ c˜ ao de queratin´ ocitos e bicamadas lip ´ ıdicas (` a direita). Adaptado
d e [ 4 ] . ................................... 1 1
2.3 Mo delo unidimensional da sup erf ´ ıcie transdutora de ultrassons [5]. . 15
2.4 Circuito equiv alen te do transdutor de ultrassom [5]. . . . . . . . . . 16
2.5 T ransp orte de f´ armaco no estrato c´ orneo (A) na condi¸ c˜ ao de difus˜ ao
passiv a e (B) sob a transmiss˜ ao de ultrassons, com forma¸ c˜ ao de mi-
crob olhas e desorganiza¸ c˜ ao da estrutura lip ´ ıdica. Adaptado de [6]. . . 21
2.6 M ´ eto dos de otimiza¸ c˜ ao em TFT. Adaptado de [7]. . . . . . . . . . . . 23
2.7 T ransp orte de f´ armaco usando ultrassons. A tuador de UTS sobre a
sup erf ´ ıcie da p ele e efeito da p ermeabiliza¸ c˜ ao das bicamadas in terce-
l u l a r e s [ 8 ] . ................................. 2 4
2.8 Princ ´ ıpio da ion toforese. Mol ´ eculas de f´ armaco eletricamen te carre-
gadas s˜ ao impulsionadas atra v ´ es da p ele a partir de for¸ cas repulsiv as
en tre o el ´ etro do e as mol ´ eculas com a mesma p olaridade. Adaptado
d e [ 9 ] . ................................... 2 7
2.9 Circuito el ´ etrico equiv alen te do estrato c´ orneo com duas vias de trans-
p orte molecular. R m e C m represen tam o diel ´ etrico da matriz lip ´ ıdica;
R a e C a referem-se ao diel ´ etrico dos ap ˆ endices cutˆ aneos. R b ´ e a re-
sist ˆ encia de uma solu¸ c˜ ao eletrol ´ ıtica onde est´ a con tida a amostra de
p ele e R C ´ e uma resist ˆ encia de medi¸ c˜ ao. C S ´ e a capacidade el ´ etrica
d a p e l e . [ 1 0 ]................................ 3 0
2.10 Efeito da ca vita¸ c˜ ao em SFE e SBF. . . . . . . . . . . . . . . . . . . . 33
2.11 Regi˜ oes de transp orte lo calizado (R TL) ap´ os exp osi¸ c˜ ao de UTS de 20
k H z [ 1 1 ] . ................................. 3 4
2.12 SonoPrep (Son tra Medical Corp oration) [12] . . . . . . . . . . . . . . 37
2.13 LidoSite (Vyteris, Inc)[13] . . . . . . . . . . . . . . . . . . . . . . . . 38
xix

LIST A DE FIGURAS
2 . 1 4 I o n s y s ( A L z a ) [ 1 4 ] ............................. 3 9
2.15 Companion 80 (Iomed) [15] . . . . . . . . . . . . . . . . . . . . . . . 39
2.16 En viron (En viron Skin Care (Pt y) Ltd ) [16] . . . . . . . . . . . . . . 40
4.1 T ransdutor Ultrassons (UTS) de 20 kHz. Diˆ ametro da face emissora,
D = 6 , 5 cm ; ............................... 5 0
4.2 T ransdutores de 1 MHz. . . . . . . . . . . . . . . . . . . . . . . . . . 51
4.3 Circuito para driving de um atuador piezo el ´ etrico [17]. . . . . . . . . 52
4.4 Circuito t ´ ıpico em s ´ erie de um oscilador [18]. . . . . . . . . . . . . . 54
4.5 El ´ etro dos para sim ula¸ c˜ ao da aplica¸ c˜ ao de f´ armaco em ion toforese. . . 55
4.6 Printe d Cir cuit Bo ar d (PCB) desen v olvida na primeira ab ordagem ao
pro jeto. Dimens˜ oes 185,00 x 119,91 mm. . . . . . . . . . . . . . . . . 59
4.7 PCB desen v olvida na segunda ab ordagem ao pro jeto. Dimens˜ oes
7 2 , 6 4 x 4 7 , 2 4 m m . ............................ 6 2
5.1 Esquema de liga¸ c˜ oes en tre os blo cos de har dwar e . ........... 6 9
5.2 Configura¸ c˜ ao do m´ odulo AD5428 - Diagrama de temp o. . . . . . . . 71
5.3 T ransa¸ c˜ ao de dois blo cos, cada um com 3 bursts de 4 bytes . ...... 7 4
5.4 Sequ ˆ encia de bytes mo delo utilizada na com unica¸ c˜ ao em s ´ erie. . . . . 75
5.5 Sequ ˆ encia de bytes mo delo para a) sonoforese 20 kHz, b) sonoforese
1 M H z e c ) i o n t o f o r e s e . .......................... 7 6
5.6 V etores de bytes com dados sobre a) tip o de tratamen to, b) in ´ ıcio/fim
da sonoforese e c) in ´ ıcio/fim ion toforese. . . . . . . . . . . . . . . . . 77
5.7 Configura¸ c˜ ao do PWM de um sinal de 20 kHz. . . . . . . . . . . . . . 79
5.8 Mo dula¸ c˜ ao do sinal no mo do de transmiss˜ ao de pulsos. . . . . . . . . 80
6.1 Esquema de rela¸ c˜ oes en tre a parte gr´ afica e a parte funcional do de-
sen v olvimen to do softwar e ......................... 8 2
6.2 Apresen ta¸ c˜ ao da In terface. . . . . . . . . . . . . . . . . . . . . . . . . 83
6.3 F uncionameno do mecanismo Dispatc her. . . . . . . . . . . . . . . . . 85
6.4 User c ase . ................................. 8 7
7.1 El ´ etro dos utilizados para teste do pro cesso de ion toforese. . . . . . . 90
7.2 User interfac e com os parˆ ametros de configura¸ c˜ ao do caso 1 de testes. 91
7.3 Caso 1 - P erformance do blo co de ion toforese sem a juste. . . . . . . 92
7.4 Caso 1 - P erformance do blo co de ion toforese ap´ os a juste no firmwar e . 92
7.5 Caso 4 - P erformance do blo co de ion toforese. . . . . . . . . . . . . . 92
7.6 Caso 5. N ´ ıv el de tens˜ ao no oscilosc´ opio. . . . . . . . . . . . . . . . . . 93
7.7 Caso 6. N ´ ıv el de tens˜ ao no oscilosc´ opio. . . . . . . . . . . . . . . . . . 93
7.8 Caso 7. N ´ ıv el de tens˜ ao no oscilosc´ opio para uma corren te de 0,2 mA. 93
7.9 P osicionamen to dos el ´ etro dos e da resist ˆ encia id ˆ en tica ` a resist ˆ encia
d a p e l e . .................................. 9 5
7.10 N ´ ıv el de tens˜ ao na transmiss˜ ao de UTS de 1 M H z a) ` a sa ´ ıda do
MOSFET, b) ` a sa ´ ıda do amplificador; N ´ ıv el de tens˜ ao na transmiss˜ ao
de UTS de 20 k H z c) ` a sa ´ ıda do MOSFET, d) ` a sa ´ ıda do amplificador. 96
7.11 Resultados da primeira ab ordagem - tens˜ ao registada aos terminais
dos transdutores recetores. . . . . . . . . . . . . . . . . . . . . . . . 97
xx

LIST A DE FIGURAS
7.12 Resultado da oscila¸ c˜ ao de um twe eter atuado p ela 1 a PCB desen v olvida. 98
7.13 Resultados da emiss˜ ao con t ´ ın ua - visualiza¸ c˜ ao das ondas de tens˜ ao
no oscilosc´ opio. Canal A: transdutor recetor: Canal B: transdutor
e m i s s o r . .................................. 9 9
7.14 Resultados da emiss˜ ao pulsada - visualiza¸ c˜ ao das ondas de tens˜ ao
no oscilosc´ opio. Canal A: terminais do transdutor recetor: Canal B:
terminais do transdutor emissor. . . . . . . . . . . . . . . . . . . . . 100
A.1 Mol ´ eculas utilizadas nos ´ ulimos anos em sonoforese de frequ ˆ encia ele-
v ada. MW: P eso Molecular; Log K o/w : co eficien te de parti¸ c˜ ao. Reti-
r a d o d e [ 1 9 ] . ................................ 1 1 6
A.2 Mol ´ eculas utilizadas nos ´ ulimos anos em sonoforese de baixa frequ ˆ encia.
MW: P eso Molecular; Log K o/w : co eficien te de parti¸ c˜ ao. Retirado de
[ 1 9 ] . .................................... 1 1 7
A.3 F´ armacos para administra¸ c˜ ao transd ´ ermica apro v ados p ela FD A. Esta
lista inclui adesiv os transd ´ ermicos e sistemas de administra¸ c˜ ao. Re-
tirado de [20] (2008). . . . . . . . . . . . . . . . . . . . . . . . . . . 118
B.1 Esquem´ atico desen v olvido relativ o ao blo co de UTS 20 kHz. . . . . . 120
B.2 Esquem´ atico desen v olvido relativ o ao blo co de UTS 1 MHz. . . . . . 121
B.3 Esquem´ atico desen v olvido relativ o ao blo co da ion toforese. . . . . . . 122
B.4 Esquem´ atico desen v olvido relativ o ao blo co do micro con trolador. . . 123
B.5 Esquem´ atico desen v olvido relativ o aos comp onen tes de alimen ta¸ c˜ ao. 124
B.6 Esquem´ atico desen v olvido relativ o ` a com unica¸ c˜ ao Universal Serial
Bus ( U S B ) . ................................ 1 2 5
B.7 Esquem´ atico desen v olvido relativ o ao blo clo de UTS - 2 a ab ordagem. 126
C.1 PCB desen v olvida, layout 2D - 1 a ab ordagem. . . . . . . . . . . . . 128
C.2 PCB desen v olvida, layout 3D - ion toforese e sonoforese 1 a ab ordagem. 129
C.3 PCB desen v olvida, layout 2D e 3D - sonoforese 2 a ab ordagem. . . . 130
D.1 Diagrama das camadas de abstra¸ c˜ ao do firm w are. . . . . . . . . . . . 132
E.1 Esquema de medi¸ c˜ ao da corren te el ´ etrica e da tens˜ ao v erificada nos
el ´ etro dos em fase de testes ao sistema de ion toforese. . . . . . . . . . 133
E.2 Medi¸ c˜ ao do sinal nos terminais do transdutor emissor e recetor em
fase de testes ao sistema de sonoforese de elev ada frequ ˆ encia - 2 a
a b o r d a g e m . ................................ 1 3 3
E.3 Bancada de teste ao sistema de ion toforese. . . . . . . . . . . . . . . . 134
E.4 Bancada de teste ao sistema de sonoforese - 2 a ab ordagem. . . . . . . 134
xxi

Lista de T ab elas
1.1 Iden tifica¸ c˜ ao dos in terv enien tes e das suas fun¸ c˜ oes no pro jeto. . . . . 2
2.1 P arˆ ametros de caracteriza¸ c˜ ao de uma onda de ultrassom. . . . . . . . 16
2.2 Principais v an tagens e limita¸ c˜ oes em sonoforese [7], [19]. . . . . . . . 26
2.3 Principais v an tagens e limita¸ c˜ oes em ion toforese. . . . . . . . . . . . . 29
2.4 Com bina¸ c˜ ao da sonoforese e ion toforese no transp orte de div ersos
a g e n t e s t e r a p ˆ e u t i c o s . ........................... 3 5
3.1 Requisitos funcionais com uns aos tr ˆ es pro cessos. . . . . . . . . . . . . 43
3.2 Requisitos funcionais relativ os ` a sonoforese de baixa frequ ˆ encia. . . . 44
3.3 Requisitos funcionais relativ os ` a sonoforese de frequ ˆ encia elev ada. . . 44
3.4 Requisitos funcionais relativ os ` a ion toforese. . . . . . . . . . . . . . . 44
3.5 Requisitos de in terface com o sistema. . . . . . . . . . . . . . . . . . . 45
3.6 Requisitos de autonomia e consumo do sistema. . . . . . . . . . . . . 45
3.7 Requisitos mecˆ anicos do sistema. . . . . . . . . . . . . . . . . . . . . 46
3.8 Requisitos de alarmes e erros do sistema. . . . . . . . . . . . . . . . . 46
3.9 Requisitos regulamen tares. . . . . . . . . . . . . . . . . . . . . . . . . 46
4.1 Compara¸ c˜ ao de caracter ´ ısticas en tre os amplificadores LM675 e LM321. 57
4.2 Caracter ´ ısticas est´ aticas e dinˆ amicas en tre mo delos de trans ´ ıstor FET. 58
4.3 Caracter ´ ısticas do sensor de temp eratura LM60. . . . . . . . . . . . . 65
5.1 Con te ´ udo dos v etores de resp osta do firmwar e duran te o tratamen to. 77
5.2 P arˆ ametros de configura¸ c˜ ao do proto colo UAR T e resp etiv os v alores. 78
5.3 N ´ ıv eis de energia p or mo dula¸ c˜ ao do sinal - 2 a ab ordagem sonoforese. . 80
6.1 M ´ eto dos da in terface (I) e funcionais (F) da CommPro vider. . . . . . 84
6.2 M ´ eto dos da in terface (I) e funcionais (F) do StateData. . . . . . . . . 86
7.1 Condi¸ c˜ oes de teste da ion toforese. (PRP: P er ´ ıo do de rep eti¸ c˜ ao pul-
sos; DC: Ciclo de trabalho; NA: N˜ ao aplic´ av el; P ol: P olaridade; C:
Con t ´ ın uo; P:Pulsado; An: Ano dal; Cat: Cato dal) . . . . . . . . . . . 90
7.2 V alor configurado e obtido para cada parˆ ametro em teste - Emiss˜ ao
con t ´ ın ua. I: amplitude da corren te; P ol: P olaridade . . . . . . . . . . 94
7.3 V alor configurado e obtido para cada parˆ ametro em teste - Emiss˜ ao
pulsada. I: amplitude da corren te; P ol: P olaridade . . . . . . . . . . . 94
xxiii

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