Design of a magnetic actuation system for a microbiota-collection ingestible capsule

Abs ac —Minimally in asi e wi eless de ices, allowing he sampling o gu ’s bac e ia, a e needed o a longi udinal unde s anding o he ole o he mic obio a on he human heal h. He ein, we p esen a no el magne ic ac ua ion sys em i ing inside a 11.5 x 30.5 mm wi eless inges ible capsule. Lacking any elec onic componen s, he capsule obo is designed o he collec ion o mic obio a’s samples h ough mechanical b ushing. Wi eless ac i a ion and in si u sampling a e enabled by an ex e nal pe manen magne ic sou ce. This componen , when app oaching he capsule, p og essi ely allows: (1) he adhesion o he de ice o he mucosa, (2) he exposu e o he b ushes, and (3) he sampling by mul iple o a ions. Nume ical and analy ical models we e de eloped o dimensioning he sys em, and we e alida ed by bench op expe imen s. I. INTRODUCTION In he las decade, subs an ial esea ch has been in es iga ing he ela ionship be ween he mic obio a/mic obiome and he human heal h [1]. By de ini ion, he mic obio a is he collec ion o 10-100 illion mic obial cells li ing in symbiosis wi h he human body, p ima ily, i.e. > 90%, in he gas oin es inal (GI) ac [2]. As shown by mul iple s udies, an al e a ion o he gu mic obial composi ion (i.e., dysbiosis) is associa ed wi h pa hogenesis o se e al diseases, e.g. diabe es, obesi y, in lamma o y bowel diseases, ca dio- ascula and also psychological diso de s [1]. Howe e , whe he he dysbiosis is a cause, a consequence, o a modula o o he disease has no been ca e ully in es iga ed ye [3]. One o he main easons o his esea ch gap, is due o he cu en in asi e echniques o sampling he mic obio a (e.g., biopsy o mucosal b ushing du ing endoscopic p ocedu es), hence limi ed only o symp oma ic pa ien s. As a solu ion, he de elopmen o non- in asi e de ices, such as inges ible wi eless capsules, would make he sampling o mic obio a mo e accessible, including * This wo k was suppo ed by he ATLAS p ojec . This p ojec has ecei ed unding om he Eu opean Union’s Ho izon 2020 esea ch and inno a ion p og amme unde he Ma ie Sklodowska-Cu ie g an ag eemen No 813782.This wo k was also pa o he CISAS (MIUR-CNR) p ojec , unded by he I alian Minis y o Uni e si y and Resea ch. M. Finocchia o, A. Menciassi and G. Ciu i a e wi h he BioRobo ics Ins i u e, Scuola Supe io e San ’Anna, I aly and wi h he Depa men o Excellence in Robo ics & AI, Scuola Supe io e San 'Anna, I aly. M. Finocchia o is also wi h Cen e o Resea ch in Biomedical Enginee ing o Uni e si a Poli ècnica de Ca alunya, Spain (co esponding au ho ’s e-mail: ma ina. inocchia [email protected]). M. Sp o ie i and C. Giosuè a e wi h Na ional Resea ch Council (CNR), Ins i u e o An h opic Impac s and Sus ainabili y in he Ma ine En i onmen (IAS), I aly. G. D ago and F. Cibella a e wi h Na ional Resea ch Council (CNR), Ins i u e o Biomedical Resea ch and Inno a ion (IRIB), I aly. he small bowel, which is so a no easible by commonly used echnologies. As a ma e o ac , his al e na i e would ha e a massi e impac in clinical esea ch, as well as in u u e mul i-modali y and in si u diagnos ic echniques [4]. In ecen yea s, ew endoscopic capsules o mic obio a collec ion ha e been in es iga ed. Salem e al. de eloped an inges ible de ice, whose opening is egula ed by he dissolu ion o a bio-g adable coa ing, allowing he en ance o he luid inside he capsule. A he same ime, he closing is enabled by a passi e bis able mechanism, igge ed by olume inc ease o a sponge. Al hough p omising, his solu ion does no enable choosing he speci ic loca ion o collec ion, nei he localizing he sample, and i does no conside he quali y, quan i y and co ec s o age o he ma e ial in o de o p ope ly analyze i s composi ion h ough he bac e ial 16S RNA sequencing [5]. A mo e ad anced solu ion is p esen ed by Rezaei e al., who collec ed he bac e ia h ough an osmo ic pump, enabled by he dissolu ion o an ex e nal coa ing. In his case, i was also possible o success ully analyze he bac e ia DNA’ samples, collec ed in in- i o condi ions. None heless, a spa ially a ge ed sampling is s ill no easible in his scena io, and he au ho s exp essed hei in en ion o use a magne ic sys em, in he u u e, o co e his gap [6]. In his amewo k, he cu en pape p esen s a no el magne ic ac ua ion sys em o a mic obio a collec ion capsule. The de ice, ee o any elec onical componen s, is designed o allow a sa e mucosa b ushing and sample s o age. In si u wi eless ac i a ion is enabled by he use o an ex e nal pe manen magne , which igge s he o a ion o minia u ized magne s inside he capsule. S a ing om he sys em equi emen s, he pape shows he design low o he ac ua ion sys em. In his con ex , a modula amewo k o he compu a ion o he magne ic o ques and o ces enabling he ac ua ion is p esen ed. Finally, p elimina y alida ion o he design, h ough nume ical and analy ical me hods and wi h bench op expe imen s, is epo ed. II. REQUIREMENTS AND CAPSULE CONCEPT A. Sys em equi emen s As an inges ible de ice, he endoscopic capsule needs o sa is y se e al limi ing equi emen s, especially in e ms o size and sa e y. Mo eo e , addi ional cons ain s a e posed by he need o collec ing and sa ely s o ing mic obio a samples. He e, we lis he main equi emen s ha need o be add essed: • Capsule dimensions lowe o equal o hose o he PillCamTM (Med onics, Minneapolis, USA), FDA app o ed inges ible de ice [7] – leng h o 32 mm and diame e o 12 mm. Ma ina Finocchia o, C is ina Giosuè, Gaspa e D ago, Fabio Cibella, A ianna Menciassi, Membe IEEE, Ma io Sp o ie i, Gas one Ciu i, Membe IEEE Design o a magne ic ac ua ion sys em o a mic obio a-collec ion inges ible capsule • Localiza ion and wi eless ac i a ion o he sampling p ocess in speci ic and selec ed loca ions. • Sa e y o he de ice, a oiding p o uding pa s, loss o componen s o elec omagne ic-associa ed isks. • Volume o he collec ed sample su icien o RNA sequencing analysis – equal o highe o 18 mg [8]. • App op ia e s o age o he collec ed sample inside he capsule. In cu en clinical p ac ise, he mic obio a sample is s o ed in a RNAla e  s abiliza ion solu ion o a oid deg ada ion, igh a e he collec ion (1:5 = olumes o RNA la e : issue). Pa allel esea ches a e in es iga ing he need o he p ese ing solu ion igh a e collec ion o he sample, o i i can be added ew hou s la e , when he capsule is expulsed [9]. • Collec ion o a leas wo simul aneous samples o egion o in e es o enable a mo e obus analysis. B. Capsule concep Gi en he small olume a ailable inside a pill-size inges ible capsule (i.e., a ound 2 mL), he use o s anda d mecha onic sys ems (i.e., mo o s, d i e s, elec onic boa ds, ba e ies) poses se e al challenges. Mo eo e , sa e y issues ela ed o he inges ion o elec ical componen s impose addi ional limi a ions. As a solu ion, ou design is buil upon an ac ua ion sys em made o only passi e componen s, ope a ed emo ely by an ex e nal pe manen magne . As shown in Fig. 1, he mechanism i s inside a 11.5 x 30.5 mm capsule and allows he mic obio a sampling h ough luminal b ushing. This clinical echnique p o ides he bes p opo ion o bac e ia o hos DNA wi h espec o he o he sampling me hods, wi hou in ol ing any bleeding [9]. In ou case, he specimen is collec ed wi h he capsule using wo o a ing b ushes (Fig. 1.d-e). Each componen has an ex e nal su ace wi h compa able dimension (i.e., 50 mm²) o hose used in clinics (i.e., Cook Medical Cy hology b ush). Each b ush, once collec ed he issue, s o es i inside a sepa a e ese oi , which is sized o house he co ec olume o RNAla e  (i.e., a leas 5 imes he olume o he sample). In ac , e en hough he manda o y use o a p ese a ion solu ion is unde in es iga ion, au ho s decided o gua an ee he needed space inside he capsule. Two ga es co e he b ushes; hei opening, oge he wi h he sampling p ocess, a e con olled emo ely (Fig. 1.d). Finally, i e N52 NdFeB in e nal pe manen magne s (IPMs) cons i u es he capsule’s ac ua ion sys em (Fig. 1.c-e). In pa icula , wo o hem ha e a hemisphe ical shape, and a e ixed a he wo ends o he capsule. Whe eas wo diame ically-magne ized hollow cylinde s a e moun ed on a sha , and igidly connec ed o he b ushes, hus allowing hei o a ion. Finally, a hi d hin hollow diame ically- magne ized cylinde , ee o o a e a ound he capsule in e nal wall, d i es he opening and closing o he ga es. A summa y o he capsule’s speci ica ions is p o ided by Table 1. The IPMs o a ions a e d i en by he a ia ion o he magne ic ield induced by an ex e nal pe manen magne (EPM). The sys em has h ee main wo king phases: (1) a ac ion o he capsule o he in es inal walls; (2) opening o he de ice; and (3) b ushing o he mucosa. As Fig. 2 shows, when he EPM is placed a a dis ance d1 om he capsule, he de ice is a ac ed o he mucosa by a o ce F. Once he EPM is mo ed o a dis ance d2 smalle han d1, he gene a ed magne ic ield o ces he o a ion o he ga es, exposing he b ushes. Las ly, when he EPM eaches a dis ance d3 lowe han d2, he o a ion o he cylind ical magne s is enabled, d i ing he b ushing. In his case, he EPM is mo ed backwa d and o wa d o a Δd a ound d3 (such ha d3-Δd < d2), allowing mul iple o a ions o he b ushes. Finally, when he sampling ask has ended, he EPM is emo ed leading o he closu e and eleasing o he capsule. III. MAGNETIC ACTUATION SYSTEM A. Magne ic p inciple The mechanism allowing he o a ion o he ga es and he b ushes, is based on wo non-linea magne ic o sional sp ings, i s ly in oduced by Simi e al. [10]. In ac , when placing wo diame ically-magne ized hollow cylinde s on a sha , a ixed sho dis ance, and ee o o a e, hey o ien hemsel es o ha e pa allel and opposi e magne iza ion Speci ica ions Values Capsule dimension 11.5 x 30.5 mm B ush ex e nal su ace 50 mm² each Rese oi size 261 mm3 each Numbe o samples 2 IPMs dimensions [mm] IPM1,5: R=5.25 IPM3: D=10, d=9, L= 7 IPM2,4: D=7, d=1.25, L=2 Figu e 1. 3D model o he endoscopic capsule: a) ex e nal iew wi h closed ga es; b) he capsule wall is emo ed o see he in e nal componen s; c) in e nal magne s a anged inside he capsule; d) he ga es (in g een), when opened, exposes he b ushes (in g ey) o he ex e nal en i onmen ; e) 3D CAD o he i e in e nal magne s and one o he wo b ushes. Figu e 2. Ope a ional low: he EPM posi ion igge s i s he adhesion o he capsule o he in es inal walls, second he opening o he ga es, and hi d he b ushing o he mucosa. TABLE 1. MAIN DESIGN SPECIFICATIONS ec o s. Howe e , i only one o he wo magne s is ixed, and an ex e nal magne ic ield wi h opposi e pola i y is applied, s ong enough o o e come he local magne ic coupling, he cylinde ee o o a e will make a 180° u n. Doing so, i will each an uns able equilib ium poin , and will s o e po en ial elas ic ene gy. Once he ex e nal magne ic ield is emo ed, he ee magne will go back o i s ini ial posi ion, eleasing he s o ed ene gy. The main pa ame e ha cha ac e izes he magne ic o sional sp ing is he in e nal o que be ween he wo magne s, when he angle be ween he co esponding magne iza ion ec o s is 90°. This is he highes le el o o que, named peak o que, ha needs o be o e come by he ex e nal magne ic agen o o a e one o he wo cylinde s. B. Analy ical desc ip ion In ou design, an ex ended e sion o he magne ic o sional sp ing is used o d i e he sys em. Mo e in de ails, e e ing o he nomencla u e o Fig. 3, IPMs 1 and 5 wo k as he ixed magne s o h ee nes ed magne ic o sional sp ings (MTS). Acco dingly, IPM3 is he ee- o- o a e elemen o he i s MTS, allowing he opening o he ga es. Whe eas IPM2 and IPM4 a e he o a ional magne s o he o he wo MTSs. In o de o co ec ly dimension he sys em o gua an eeing he desi ed beha io , and c ea e a scalable amewo k, a s a ic model has been de eloped. Assuming ha he en i onmen does no con ain any addi ional e omagne ic ma e ial, i is possible o apply he p inciple o supe posi ion o he compu a ion o o ques and o ces induced by mul iple magne s. Fig. 3.a shows he o ien a ion o he magne s in he es posi ion (i.e., ga es closed and capsule ee o na iga e in he bowel). In his con igu a ion, he in e nal o que exe ed by he magne s ixed o he capsule (i.e., IPM1,5) on hose ee o o a e (i.e., IPM2,3,4), has o gua an ee he s able closu e o he capsule:  +    +  ()  +    +  () Whe e, is he o que on IPM2 gi en by IPM1, is he o que on IPM2 gi en by IPM5, e c. Since he sys em is axially symme ic, he o que expe ienced by IPM2 is equal o he one o IPM4, and he same applies o o ques on IPMs 1 and 5. Conside ing Fig. 3.a, as he i s s ep owa ds he sampling p ocess, he EPM placed a a dis ance d1 om he capsule, need o gene a e an axial magne ic ield g adien such ha : F (d) = F1 - 2F2 - F3 – mg > 0 () F1 = F5, F2 = F4. () Whe e F is he o al e ical o ce exe ed on he capsule, F1, F2 and F3 e e espec i ely o he magne ic e ical o ce on IPM1,2,3 and mg is he capsule weigh o ce o o e come o ensu e he adhesion o he sys em o he in es inal mucosa. Secondly, placing he EPM close o he capsule (Fig. 3.b), a a dis ance d2 < d1, he o que induced by he EPM on IPM3 (i.e., 36), mus o e come he in e nal o ques be ween IPM3 and he IPMs 1 and 5, hus allowing o open he ga e:  (d)   −  () A his s age, he b ushes do no o a e ye , so he ex e nal magne ic ield does no o e come he in e nal o ques on IPMs 2 and 4:  (d)   +  −  +  () Finally, mo ing he EPM a a dis ance d3 om he capsule (such ha d3 < d2), he ex e nal o que on IPMs 2 and 4 o e come he in e nal couplings, hus allowing he o a ion o hese wo magne s (Fig. 3.c), while keeping he ga es opened:  (d)   +  −  +  () IV. MAGNETIC MODELLING A. Design wo k low The dimensioning o he ac ua ion sys em has in ol ed mul iple s eps in o de o mee he design equi emen s. Conside ing he maximum olume o he capsule and lea ing space o he wo ese oi s o RNAla e , he in e nal magne s sizing is a ade-o be ween s abili y and ex e nal magne ic ac i a ion. As a ma e o ac , he bigge he in e nal o que on he IPM3, he mo e obus is he closu e o he ga es. Howe e , i implies also ha ing a bigge ex e nal magne o emo e ac i a ion. Hence, i s he IPMs we e dimensioned and hei ela i e dis ances compu ed. Secondly, he magne ic ield able o o e come he o ques on he IPMs du ing he opening and b ushing phase was compu ed. Finally, he EPM able o p o ide he compu ed ield was selec ed, and he ope a ional dis ances om he capsule, o each wo king phase, we e assessed. The op imal olume, shape and ype o magne iza ion o he EPM we e in es iga ed o p o ide an almos uni o m magne ic ield a he capsule si e. To his end, wo models we e used o sol ing he sys ems o equa ions: one analy ical and one nume ical. The analy ical modelling is an implemen a ion o he cha ge and cu en model o app oxima ing he magne ic ield lux densi y, in e ac ion o ces and o que de i ing om a magne ic sou ce [11]–[13]. The amewo k was de eloped using Ma lab (Ma hwo ks). Whe eas he nume ical model in ol es he solu ion o he magne os a ic equa ions using he Fini e Elemen Me hod (FEM) wi h he so wa e COMSOL Mul iphysics® (S ockholm, Sweden). Las ly, o a inal alida ion o he modelling amewo k, bench op expe imen s we e conduc ed wi h es magne s (Sec ion V). Figu e 3. Diag am o he h ee ope a ional phases and he pola iza ion o he IPMs: a) capsule con igu a ion in es posi ion, he EPM gene a e an a ac ion o ce on he IPMs; b) he EPM mo es o wa d igge ing he IPM3 o a ion ( i s uns able equilib ium poin ); c) he EPM mo es close , enabling he o a ion o IPM2 and IPM4 (second uns able equilib ium poin ) and he consequen b ushing. . B. In e nal o ques be ween IPMs The dimensions o he in e nal magne s we e maximized, o inc ease he o que gene a ed by he EPM on he IPMs. As a ma e o ac , bigge magne s expe ience highe o ques and o ces unde a ixed magne ic ield. The inal alues a e epo ed in Table 1. All he magne s a e NdFeB wi h N52 magne iza ion g ade, he highes a ailable (i.e., B =1.45T). As a second s ep, a se o simula ions was conduc ed o in es iga e he op imal solu ion o loca ing he magne s inside he capsule. To his end, he in e nal o ques, o he h ee wo king phases we e compu ed a ying he leng h o he capsule om 26.5 o 30.5 mm, wi h s eps o 1 mm. This speci ic ange alls be ween he leng h o he Pillcam™ SB3 (i.e., 26.2 mm) and he Pillcam™ Colon (i.e., 32.3 mm), lea ing ew mm om he maximum leng h o accoun o any addi ion ex e nal co e s o shea hs ha migh inc ease he inal size. Meanwhile, he su ace-su ace dis ance be ween IPM1 and IPM2 was a ied om 0.5 mm o 4 mm wi h s eps o 0.5 mm. The esul s a e shown in Fig. 4. As he bes ade- o be ween s abili y (low in e nal o ques cause he capsule o open oo easily, e en when no desi ed) and emo e ac i a ion, he capsule dimensions we e es ablished, in he i s place, o 28.5 mm, and maximum dis ance be ween IPMs 1 and 2 (i.e., d =3 mm). Acco dingly, he o que needed o o a e he IPM3 du ing he opening phase is 3.7 mNm, and o o a e IPMs 2 and 4 du ing he b ushing is 6.05 mNm (solu ion compu ed analy ically). These alues a e p o ided by an ex e nal uni o m magne ic luid densi y o a leas B=30 mT (opening) and B=75 mT (b ushing), as esul ing om a second se o simula ions. C. Ex e nal o ques induced by an EPM on he IPMs The i s s ep owa ds he selec ion o he EPM was choosing i s op imal shape and he ype o magne iza ion, a a ixed olume, inducing he highes o ques on IPM2 and IPM3. Following, he olume can be scaled o allow he p ope igge ing o he opening and b ushing phase, a dis ances compa ible wi h he ana omy o he pa ien . As a esul o an ini ial pilo expe imen a ion, an EPM olume o a ound 1000 cm3 is needed o ac i a e IPMs 2 and 4 a a dis ance o 100 mm, which is he usual ange used o endoscopic magne ic locomo ion [10]. Hence, ixing he olume o he EPM o 1000 cm3, he o que on IPM2 induced by se e al cylinde s wi h axial and diame ical magne iza ion, and cubes, wi h di e en sizes a io we e compu ed (EPMs B =1.45T), a a iable dis ances. The esul s a e shown in Fig. 5, and highligh ha he highes o que is p o ided by he axially-magne ized cylinde wi h dimensions: D=15 cm L=5,6 cm. Wi h hese dimensions, he EPM o e come he IPM2 peak o que a a dis ance o 100 mm om he capsule (su ace- o- su ace) and he IPM3 peak o que a 160 mm. Hence, e e ing o Fig. 3, d2 could be se o 160 mm (opening), and d3 o 100 mm (b ushing). These alues all in he ange usually conside ed as he a e age dis ance be ween an endoscopic capsule and he skin, o people wi h a no mal body mass index (BMI) [10]. Howe e , gi ing he scalabili y o he amewo k and he lack o any es ic ion on he size o he ex e nal ac ua o , he EPM olume migh be inc eased in he u u e o be compa ible wi h pa ien s ha ing highe BMI. V. EXPERIMENTAL VALIDATION To assess he magne ic models and e i y he p edic ed o ques, a se ies o ou bench op expe imen s we e conduc ed (named A, B, C, D). Since capsule’s selec ed magne s equi e a cus om p oduc ion, high cos and long deli e y imes, easy- o-acqui e and comme cially-a ailable magne ic cylinde s ha e been used o es ing he model. Each es equi ed he use o a obo ic a m (RV-3SB, Mi subishi Co p., Tokyo, Japan) o high p ecision egula ion o he dis ances. A iaxial o ce/ o que senso , (Nano 17-E, ATI Indus ial Au oma ion, U.S.) was used in es s A and B o measu ing he o ques. Each ime, he i e eadings om he senso we e acqui ed, and i s a e age alue was used as a e e ence. Fo all he ou expe imen s, he suppo s we e ei he 3D p in ed in ABS, o manu ac u ed wi h Te lon® and aluminum o a oid magne ic in e e ences. The sc ews used o ix he suppo s and he sha we e non- e omagne ic (i.e., Figu e 5. To ques induced on IPM2 by di e en EPM wi h ixed olume o 1000 cm3, a a iable dis ances IPM-EPM ( esul s o he analy ical model). The EPMs in es iga ed a e axially magne ized cylinde s, diame ically magne ize cylinde s, and cubes. The ed line shows he peak o que o IPM2, which when eached, allow o o a e he magne (b ushing). Figu e 4. Peak o que cu es o IPM2 and IPM3 a ying he leng h o he capsule (L [mm]) and he dis ance be ween IPM1 and IPM2 ( esul s o he analy ical model). These alues a e hose ha need o be o e come by he EPM o open he ga e (3) and b ush he mucosa (2). aluminum, Te lon®). Each es was epea ed i e imes, and he esul s ob ained we e compa ed wi h he p edic ed alues o bo h he analy ical and nume ical models. A. Tes A A i s s ep in assessing he model was o alida e he es ima ed o que be ween wo concen ic cylind ical magne s, a ying hei ela i e dis ance and angle. This con igu a ion is he one used o es ima ing he in e nal o ques be ween he IPMs. To his end, wo iden ical hollow cylinde s wi h diame ical magne iza ion (NdFeB 35H, B =1.17 T, L=6 mm, D=8 mm and d=2 mm) we e used. As shown in Fig. 6.a, one magne was ixed o he bench op, while he o he one was a ached o he load cell h ough a connec o made in aluminum, long enough o a oid any in e e ences o he senso wi h he magne ic ield. The load cell was hen a ached o he obo ic a m, o con ol he magne posi ion. In a i s es (Tes A.1), he wo cylinde s we e placed one in on o he o he , wi h a 90° misma ch be ween hei pola iza ion ec o s, and a su ace- o-su ace dis ance anging om 5 o 57 mm, conside ing 1 mm s eps. In a second es (Tes A.2), he dis ance be ween he cylinde s was ixed o 10 mm, and he magne a ached o he obo was o a ed om 0 o 360°, wi h s eps o 30° each. In bo h cases, o each s ep, he axial o que was eco ded and no ed. B. Tes B The second expe imen al se -up was designed o alida e he o que es ima ed be ween one IPM and he EPM. As in he p e ious expe imen , one diame ically magne ized cylinde (NdFeB 35H, B =1.17 T, L=6 mm, D=8 mm and d=2 mm) was a ached o a load cell, connec ed o he obo ic a m. Howe e , in his case, a bigge cylind ical magne (NdFeB N35, B =1.35 T, D=50 mm and L=25 mm), wi h axial magne iza ion, was ixed o he bench op. In he i s es (Tes B.1), he magne a ached o he obo ic a m was p og essi ely mo ed owa ds he ixed magne om a dis ance o 34 o 12 mm, wi h 1 mm s eps. Meanwhile, he angle be ween he wo magne iza ion ec o s was ixed o 90° as shown in Fig. 6.b. Whe eas, in he second es (Tes B.2), he dis ance su ace- o-su ace be ween he wo componen s was ixed o 50 mm, and he IPM was o a ed a ound i s main axis om an angle o 0° o 180°, wi h s eps o 30°. In bo h cases, a each s ep, he o que was eco ded by he load cell and no ed down. C. Tes C The hi d se o expe imen s aimed a alida ing he magne ic o sional sp ing model, and he es ima ed ope a ional dis ance o he EPM. In his case, he wo cylind ical magne s used in he i s es (i.e., B =1.17 T, L= 6 mm, D=8 mm and d=2 mm) we e moun ed on a sha , which was ixed h ough a suppo o he bench op (Fig. 6.c). One magne was ixed, while he o he ( ee o o a e), was placed a a su ace- o-su ace dis ance o 6.5 mm om he i s one. A disk made o a low ic ion ma e ial (i.e., Te lon®) was used as a space o he magne s. The p e iously in oduced axially-magne ized cylinde , was a ached o he obo ic a m using a non- e omagne ic connec o (B =1.35 T, D=50 mm and L=25 mm). S a ing om a dis ance o 100 mm om he IPMs, he EPM was p og essi ely mo ed o wa d. The dis ance IPM-EPM a which he magne ee o o a e made a u n o 180° was no ed. D. Tes D Finally, he las expe imen was designed o es he whole sys em. In his case, i e di e en diame ically magne ized hollow cylinde s, esembling hose sized o he capsule, we e moun ed on a suppo . The mos ex e nal magne s (in Fig. 6.d IPMs 1 and 5) we e ixed (NdFeB 35H, B =1.17 T, L=6 mm, D=8 mm and d=2 mm), as in he endoscopic capsule. Two addi ional hollow cylinde s (Sm2Co17 YXG30, B =1.08 T, L=2 mm, D=8 mm, d=2 mm), ep oducing IPMs 2 and 4, we e spaced (su ace- o- su ace) 2 mm apa , om he closes ixed magne , and le ee o o a e. Finally, a hin cylinde (Sm2Co17 YXG30, B =1.08 T, L=4 mm, D=12 mm and d=8.5 mm) was moun ed on a cylind ical suppo , ixed o he sha . This magne , mimicking IPM3, was le ee o o a e, and was spaced 2 mm espec i ely om magne s 2 and 4 (see Fig. 6.d). All he space and he suppo we e buil in Te lon®, o minimize he con ac ic ion. The p e iously men ioned axially- magne ized cylinde (B =1.35 T, D=50 mm and L=25 mm), was a ached o he obo ic a m, wi h i s su ace cen e ing he magne s moun ed on he suppo . The cylinde was mo ed om a dis ance o 130 mm owa ds he IPMs. The poin s in which magne s 2 and 4 and magne 3 u ned was eco ded. E. Resul s The aim o he expe imen s was o alida e he modelled o ques, o ces and EPM ope a ional dis ances. The esul s a e summa ized in Table 2. To his end, Tes A and B Figu e 6. a) Expe imen al se up o alida e he in e nal o que be ween wo IPMs a ying hei ela i e dis ance d and he angle θ; b) expe imen al se up o alida e he o que induced by he EPM on a IPM a ying hei ela i e dis ance d and he angle θ; c) expe imen al se up o alida e he dis ance a which he EPM igge s he magne ic o sional sp ing, and allows he o a ion o an IPM; d) expe imen al se up o alida e he dis ances a which he EPM igge s he o a ion o IPM3 (opening) and IPM2,4 (b ushing). p o ided good esul s, ha ing he expe imen al o que cu es o e lapping wi h he es ima ed ones (see Fig. 7); o Tes A.2, FEM ou pe o med he analy ical solu ion. Rega ding Tes C a sligh misma ch be ween simula ed and eal esul s was epo ed. This is p obably due o he non-pe ec alignmen be ween he EPM and IPM cen e , which induces addi ional o ques ha con ibu e o he o a ion o he IPM (happening a a sligh u he dis ance IPM-EPM han he simula ed one). Finally, in Tes D, bo h IPM3 and IPM2,4 o a ed when he EPM was close o he es ima ed ope a ional dis ance. The eason o his obse ed beha io comes om an addi ional esis i e ac o which con ibu e o he o e all axial o que o he IPM. As a ma e o ac , while o a ing unde he in luence o he EPM, he IPMs expe ience in e nal a ac i e/ esis i e magne ic o ces and sligh o ques on he o he wo axes. These, oge he wi h he con ac ic ion, inc ease he o e all mechanical o que on IPM3 o a 30%. Whe eas, o IPM2,4, i doubles he esis i e peak o que. VI. DISCUSSION AND CONCLUSION In his pape , we p esen a no el magne ic ac ua ion sys em o an inges ible capsule designed o enabling he collec ion o mic obio a samples h oughou he whole GI ac . The sys em allows in si u sampling o he mic obio a, and emo e ac i a ion wi h an ex e nal pe manen magne . Localiza ion o he sys em is possible, pe o ming iangula ion o he magne ic lux densi y measu ed wi h ex e nal Hall e ec senso s (e.g., asking he pa ien o wea a bel wi h hall e ec senso s) [14]. Howe e , i s de elopmen is ou o he scope o his pape . The passi e na u e o he magne s, eplacing s anda d elec ical componen s, in insically makes he sys em sa e and easie o ansla e in he clinical p ac ice. The ac ua ion sys em, based on mul iple magne ic o sional sp ings, was dimensioned h ough a scalable amewo k, based on nume ical and analy ical simula ions. The alidi y o he compu a ional model and he unc ions o he ac ua ion sys em we e e alua ed expe imen ally wi h a se ies o bench op es s. Acco dingly, a scaled se -up assessed he alidi y o he compu ed o ques and e i ied he o e all ope a ions o he sys em. To his end, he expe imen al pla o m included a se o pe manen magne s wi h sligh bigge size o hose designed o he inal p o o ype. The es s allowed o es ima e a esis i e mechanical ac o which con ibu es o he o que on he IPMs o a second- ound design and inal implemen a ion. As a inal s ep, conside ing he disco e y o he co ec i e pa ame e h ough he expe imen s, he p o o ype design is modi ied. Acco dingly, he inal capsule leng h is se o 30.5 mm. Doing so, he pu e magne ic peak o que on IMP2,3,4 is dec eased. Following, he size o he EPM is inc eased o L=73 mm and D=195 mm: o allow he ac i a ion despi e he addi ional esis i e con ibu ion on he IPMs o ques. In his way he new EPM ope a ional dis ances a e d2=200 mm (i.e., opening) and d3=100 mm (i.e., b ushing), s ill compa ible wi h ope a ing dis ances. As a ma e o ac , he inal dimensioning is made in o de o keep he minimum dis ance capsule (IPMs)-EPM (i.e., d3) o 100 mm, which is a easonable es ima ion o he a e age dis ance be ween he skin and he bowel [10]. In his way, he EPM dimensions we e modi ied main aining he shape, ype o magne iza ion, and he dimensional a io be ween he diame e and he heigh , se in Sec ion IV and conside ed op imal. Wi h a inal olume o 2179 cm3, and a weigh o 16.3 kg, he EPM migh be ixed o a suppo i e a m (e.g., Ma in’s A m), and manipula ed by hands om he clinician. The design pa ame e s, de i ed om he alida ed compu a ional models and he bench op expe imen s, will enable he au ho s o build he inal capsule p o o ype. Hence, all he componen s will be moun ed inside a bio- compa ible case and a se o u u e expe imen s will aim a assessing he abili y o he designed de ice o collec and s o e mic obio a samples, in ex- i o and in- i o scena ios. Fo eseen challenges include ensu ing he sealing o he capsule, o a oid any con amina ion o he samples, bu keeping he ic ion o ces low. Possible solu ions migh in ol e a combina ion o di e en echnologies, e.g., silicon- based plugs, expanding hyd ogels, eccen ic o a ional mechanism and ex e nal en e ic co e ings. TABLE 2. SUMMARY OF RESULTS OF TEST A AND TEST B Tes Es ima ed o que e o (Mean ± SD) Analy ical s expe imen al da a Nume ical s expe imen al da a A.1 0.02±0.02 mNm 0.05±0.04 mNm A.2 0.1 ± 0.04 mNm 0.08±0.02 mNm B.1 0.13±0.05 mNm 0.21±0.12 mNm B.2 0.02±0.02 mNm 0.03±0.01 mNm Es ima ed dis ance Expe imen al dis ance (Mean ± SD) Analy ical model Nume ical model C 77 mm (Δ=5 mm) 76 mm (Δ=6 mm) 82±1.4 mm D Open: 105 mm B ush: 32 mm Open: 110 mm B ush: 32 mm Open: 95 ±4.5 mm B ush: 18 ± 3 mm Figu e 7. To que cu es ob ained om es s A and B; compa ison o expe imen al esul s, wi h he analy ical and nume ical models. REFERENCES [1] E. N. 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