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Confocal laser endoscopy bụ usoro ọhụrụ nke ezigbo biopsy anya.Enwere ike nweta ihe oyiyi fluorescent nke àgwà histological ozugbo site na epithelium nke akụkụ ahụ oghere.Ugbu a, a na-eji ngwa nyocha nyocha nke a na-ejikarị eme ihe n'ụlọ ọgwụ, na-enwe oke mgbanwe na njikwa nlebara anya.Anyị na-egosipụta iji ihe nyocha ihe nlegharị anya parametric etinyere na njedebe dị anya nke endoscope iji mee mgbagha akụkụ dị elu.Etinyere oghere n'ime etiti ihe ntụgharị iji tụgharịa ụzọ ọkụ.Nhazi a na-ebelata nha nke ngwá ọrụ na 2.4 mm na dayameta na 10 mm n'ogologo, na-enye ohere ka ọ gafere n'ihu site na ọwa ọrụ nke endoscopes ahụike.Igwe oghere kọmpat na-enye mkpebi mpụta na axial nke 1.1 na 13.6 µm, n'otu n'otu.A na-enweta anya ọrụ nke 0 µm na oghere nlele nke 250 µm × 250 µm na ọnụego etiti ruo 20 Hz.Mmasị na 488 nm na-akpali fluorescein, ihe FDA kwadoro maka ọdịiche anụ ahụ dị elu.Emegharịrị Endoscopes maka okirikiri iri na asatọ na-enweghị ọdịda site na iji ụzọ ịgba ọgwụ mgbochi ọrịa akwadoro.A na-enweta ihe oyiyi fluorescent site na mucosa colonic nkịtị, tubular adenomas, hyperplastic polyps, ulcerative colitis, na Crohn's colitis n'oge colonoscopy na-emekarị.Enwere ike ịmata otu mkpụrụ ndụ, gụnyere colonocytes, mkpụrụ ndụ goblet, na sel mkpali.Enwere ike ịmata njirimara mucosal dị ka ihe owuwu crypt, cavities crypt, na lamina propria.Enwere ike iji ngwá ọrụ ahụ mee ihe dị ka ihe mgbakwunye na endoscopy omenala.
Confocal laser endoscopy bụ usoro onyonyo ọhụụ ewepụtara maka ojiji ụlọ ọgwụ dịka mgbakwunye na endoscopy oge niile1,2,3.Enwere ike iji ngwa ndị a na-agbanwe agbanwe, nke jikọtara fiber-optic iji chọpụta ọrịa ndị dị n'ime mkpụrụ ndụ epithelial na-ejikọta akụkụ ahụ oghere, dị ka eriri afọ.Ngwunye anụ ahụ dị gịrịgịrị na-arụ ọrụ nke ukwuu ma bụrụkwa isi iyi nke ọtụtụ usoro ọrịa dịka ọrịa kansa, ọrịa na mbufụt.Endoscopy nwere ike nweta mkpebi nke subcellular, na-enye ezigbo oge, àgwà dị nso na akụkọ ihe mere eme na ihe oyiyi vivo iji nyere ndị dọkịta aka ime mkpebi ụlọ ọgwụ.Biopsy anụ ahụ na-ebute ihe ize ndụ nke ọbara ọgbụgba na perforation.A na-anakọtakarị ụdị biopsy dị ukwuu ma ọ bụ ole na ole.Ihe nlele ọ bụla ewepụrụ na-abawanye ọnụ ahịa ịwa ahụ.Ọ na-ewe ụbọchị ole na ole ka onye na-ahụ maka ọrịa ga-enyocha ihe nlele ahụ.N'ime ụbọchị ichere maka nsonaazụ pathology, ndị ọrịa na-enwekarị nchekasị.N'ụzọ dị iche, usoro nyocha ụlọ ọgwụ ndị ọzọ dị ka MRI, CT, PET, SPECT, na ultrasound enweghị mkpebi gbasara ohere na ọsọ oge achọrọ iji jiri anya nke uche hụ usoro epithelial na vivo na ezigbo oge, mkpebi subcellular.
A na-ejikarị ngwá ọrụ nyocha (Cellvizio) eme ihe ugbu a n'ụlọọgwụ iji mee "nyocha anya".Nhazi ahụ dabere na ngwugwu fiber optic na-emekọ ihe ọnụ4 nke na-anakọta ma na-ebufe onyonyo fluorescent.Otu isi eriri fiber na-arụ ọrụ dị ka “oghere” iji nzacha ọkụ nlegharị anya maka mkpebi subcellular.A na-eme nyocha nso nso site na iji nnukwu galvanometer buru ibu.Ndokwa a na-egbochi ikike nke ngwa njikwa elekwasị anya.Nhazi nke ọma nke carcinoma epithelial n'oge na-achọ ịhụ anya n'okpuru anụ ahụ iji nyochaa mbuso agha wee chọpụta ọgwụgwọ kwesịrị ekwesị.A na-enye Fluorescein, onye na-ahụ maka ọdịiche nke FDA kwadoro, n'ime intravenously iji gosipụta njirimara nhazi nke epithelium. Ndị a endomicroscopes nwere akụkụ <2.4 mm na dayameta, enwere ike ibufe ya ngwa ngwa site na ọwa biopsy nke endoscopes ahụike ọkọlọtọ. Ndị a endomicroscopes nwere akụkụ <2.4 mm na dayameta, enwere ike ibufe ya ngwa ngwa site na ọwa biopsy nke endoscopes ahụike ọkọlọtọ. Эty эndomykroskopy immechut razmerы <2,4 mm na dyametre na magut bыt legko provedenы cherez yịm h эndoskopov. Ndị a endomicroscopes bụ <2.4 mm na dayameta ma nwee ike ịfefe ngwa ngwa site na ọwa biopsy nke endoscopes ahụike.Ndị a borescopes bụ ihe na-erughị 2.4 mm na dayameta ma dị mfe na-agafe na ọwa biopsy nke ọkọlọtọ borescopes ọgwụ.Mgbanwe a na-enye ohere maka ọtụtụ ngwa ụlọ ọgwụ na-adabere na ndị na-emepụta endoscope.Emeela ọtụtụ ọmụmụ ụlọ ọgwụ site na iji ngwaọrụ onyonyo a, gụnyere nchọpụta mmalite nke ọrịa cancer nke esophagus, afọ, eriri afọ, na oghere ọnụ.Emepụtala usoro onyonyo onyonyo yana ewepụtala nchekwa nke usoro ahụ.
Sistemụ Microelectromechanical (MEMS) bụ teknụzụ siri ike maka imepụta na imepụta obere usoro nyocha ejiri na njedebe njedebe nke endoscopes.Ọnọdụ a (ihe metụtara nso nso) na-enye ohere maka mgbanwe dị ukwuu na ịchịkwa ọnọdụ elekwasị anya5,6.Na mgbakwunye na ntụgharị ihu, usoro dịpụrụ adịpụ nwekwara ike ịme nyocha axial, nyocha ihe nleba anya, na nyocha ohere enweghị ohere.Ikike ndị a na-eme ka ajụjụ ọnụ sel epithelial zuru oke karịa, gụnyere onyonyo akụkụ kwụ ọtọ7, nnukwu nlele anya (FOV) 8 nyocha na-enweghị nhụsianya, yana arụ ọrụ dị mma na mpaghara mpaghara akọwapụtara nke onye ọrụ9.MEMS na-edozi nsogbu siri ike nke ịkwakọba igwe nyocha na oke ohere dị na njedebe nke ngwa ahụ.Tụnyere nnukwu galvanometers, MEMS na-enye arụmọrụ dị elu n'obere nha, oke ọsọ na ike dị ala.Enwere ike ịbawanye usoro mmepụta ihe dị mfe maka mmepụta oke na ọnụ ala.Ọtụtụ atụmatụ MEMS ka akọpụtala mbụ10,11,12.Ọ dịghị nke ọ bụla n'ime teknụzụ emebebeghị nke ọma iji mee ka ojiji ụlọ ọgwụ na-eme ihe ozugbo na vivo onyonyo site na ọwa ọrụ nke endoscopy ahụike.N'ebe a, anyị bu n'obi igosi iji ihe nyocha MEMS na njedebe njedebe nke endoscope maka in vivo ihe oyiyi mmadụ n'oge endoscopy ụlọ ọgwụ.
Emepụtara ngwa fiber optic site na iji nyocha MEMS na njedebe dị anya iji nakọta ezigbo oge na onyonyo fluorescent vivo nwere njirimara akụkọ ihe mere eme.A na-ejikọta eriri otu ụdị (SMF) na tube polymer na-agbanwe ma nwee obi ụtọ na λex = 488 nm.Nhazi a na-ebelata ogologo nke n'ọnụ dị anya ma na-enye ohere ka ọ gafere n'ihu site na ọwa ọrụ nke endoscopy ahụike ọkọlọtọ.Jiri ọnụ ọnụ ka etiti optic.Emebere anya anya ndị a iji nweta mkpebi axial dị iche iche na oghere ọnụọgụ (NA) = 0.41 na anya ọrụ = 0 µm13.A na-eme shims nkenke ka ọ kwekọọ n'ụzọ ziri ezi na ngwa anya 14. A na-etinye ihe nyocha ahụ na endoscopy nwere n'ọnụ anya anya siri ike 2.4 mm na dayameta na 10 mm ogologo (Fig 1a).Akụkụ ndị a na-enye ohere ka e jiri ya mee ihe na ụlọ ọgwụ dịka ngwa ngwa n'oge endoscopy (Fig 1b).Ike kachasị nke ihe omume laser na anụ ahụ bụ 2mW.
Confocal laser endoscopy (CLE) na nyocha MEMS.Foto na-egosi (a) ngwa ngwugwu nwere akụkụ dị nhịahụ siri ike nke 2.4 mm dayameta na ogologo 10 mm na (b) ụzọ kwụ ọtọ site na ọwa ọrụ nke endoscopy ahụike ọkọlọtọ (Olympus CF-HQ190L).(c) Nlele ihu n'ihu ihe nyocha na-egosi ihe ntụgharị nwere oghere etiti nke 50 µm nke ọkụ mkpali na-agafe.A na-agbanye ihe nyocha ahụ na gimbal nke ọtụtụ draịvụ quadrature comb mbanye na-anya.A na-ekpebi ugboro resonant nke ngwaọrụ site na nha nke mmiri torsion.(d) Nlele akụkụ nke nyocha na-egosi nyocha nke etinyere na nkwụnye nwere wires ejikọrọ na arịlịka electrode nke na-enye ebe njikọ maka mbanye na akara ike.
Usoro nyocha ahụ nwere ihe mgbanaka gimbal na-agbanye n'isi nke ọtụtụ ihe na-arụ ọrụ quadrature na-achị achị na-emegharị ka ọ na-atụgharị osisi ahụ n'akụkụ (ụgbọelu XY) n'ụdị Lissajous (Fig 1c).Oghere dị 50 µm na dayameta ka etinyere n'etiti ebe ọkụ mkpali ahụ gafere.A na-ebugharị ihe nyocha ahụ na ugboro ole na-emepe emepe, nke enwere ike ịmegharị ya site na ịgbanwe akụkụ nke mmiri torsion.Edebere arịlịka electrode na mpụta ngwaọrụ iji nye njikọ njikọ maka akara ike na njikwa (Fig 1d).
A na-etinye usoro ihe onyonyo n'ụgbọ a na-ebugharị ebugharị nke enwere ike ịbanye n'ime ụlọ ịwa ahụ.Emebere onye ọrụ eserese eserese iji kwado ndị ọrụ nwere ihe ọmụma teknụzụ pere mpe, dịka ndị dọkịta na ndị nọọsụ.Jiri aka lelee ugboro mbanye nyocha, ọnọdụ beamform, na onyonyo FOV.
Ogologo endoscope n'ozuzu bụ ihe dịka 4m iji kwe ka ị nweta ngwa ngwa n'ụzọ zuru ezu site na ọwa ọrụ nke endoscope ahụike (1.68m), yana ogologo ogologo maka ịmegharị ahụ.Na njedebe nso nke endoscope, SMF na wires na-akwụsị na njikọ ndị jikọtara na eriri optic na wired ọdụ ụgbọ mmiri nke ọdụ ọdụ.Nrụnye ahụ nwere laser, ihe nzacha, ihe nrịba elu voltaji na ihe nchọpụta fotomultiplier (PMT).Igwe ampilifaya na-enye ike na akara mbanye na nyocha.Ngalaba nzacha anya na-ejikọta mkpali laser na SMF ma na-ebufe fluorescence na PMT.
A na-emegharị Endoscopes mgbe usoro ọgwụgwọ ọ bụla gasịrị site na iji usoro ịgba ọgwụ mgbochi STERRAD ma nwee ike idi ihe ruru okirikiri iri na asatọ na-enweghị ọdịda.Maka ngwọta OPA, ọ dịghị ihe ịrịba ama nke mmebi ahụ ka a hụrụ mgbe ihe karịrị usoro nje nje 10 gasịrị.Nsonaazụ OPA karịrị nke STERRAD, na-atụ aro na ndụ endoscopes nwere ike ịgbatị ya site n'ịkwasa akwa dị elu karịa imegharị nwa nwanyị ọzọ.
Ekpebiri mkpebi onyonyo site na ọrụ mgbasa ebe site na iji bead fluorescent nwere dayameta nke 0.1 μm.Maka mkpebi n'akụkụ na axial, a tụrụ obosara zuru oke na ọkara kachasị (FWHM) nke 1.1 na 13.6 µm, n'otu n'otu, (Fig 2a, b).
Nhọrọ onyonyo.Mkpebi n'akụkụ (a) na axial (b) nke optics na-elekwasị anya bụ ọrụ mgbasa ozi (PSF) tụrụ site na iji microspheres fluorescent nwere dayameta nke 0.1 μm.A tụrụ obosara n'uju na ọkara kacha (FWHM) bụ 1.1 na 13.6 µm, n'otu n'otu.Ntinye: egosipụtara echiche agbasawanye nke otu microsphere na ntụgharị ntụgharị (XY) na axial (XZ).(c) Foto fluorescent enwetara site na ọkọlọtọ (USAF 1951) lekwasịrị anya warara (oval oval) na-egosi na enwere ike idozi otu 7-6 nke ọma.(d) Onyonyo nke dayameta 10 µm gbasasịrị microspheres fluorescent na-egosi oghere onyonyo nke 250 µm × 250 µm.Ejiri MATLAB R2019a (https://www.mathworks.com/) rụọ ndị PSF dị na (a, b).(c, d) Eji LabVIEW 2021 chịkọtara onyonyo na-egbuke egbuke (https://www.ni.com/).
Ihe oyiyi fluorescent sitere na lenses ọkọlọtọ ọkọlọtọ na-amawa nke ọma n'ụzọ doro anya nhazi nke ogidi na otu 7-6, nke na-ejigide mkpebi dị elu (Fig 2c).Ekpebiri mpaghara nlele (FOV) nke 250 µm × 250 µm site na onyonyo nke 10 µm dayameta nke eriri fluorescent gbasasịrị na mkpuchi mkpuchi (Fig 2d).
A na-emejuputa usoro akpaghị aka maka njikwa uru PMT na nhazi oge n'ime usoro onyonyo ụlọ ọgwụ iji belata ihe ndị na-emegharị ahụ site na endoscopes, colon peristalsis, na iku ume onye ọrịa.A kọwawo algọridim nrụgharị onyonyo na nhazi mbụ14,15.A na-achịkwa uru PMT site n'aka onye na-ahụ maka ịdị n'otu (PI) iji gbochie saturation siri ike16.Sistemu na-agụ oke pixel ike maka etiti ọ bụla, na-agbakọ nzaghachi nha anya na nke jikọtara ọnụ, wee kpebie uru PMT nwetara iji hụ na ike pixel dị n'ime oke ikike.
N'oge onyonyo in vivo, ndakọrịta oge n'etiti mmegharị nyocha na akara njikwa nwere ike bute inyoghi onyonyo.Mmetụta dị otú ahụ nwere ike ime n'ihi mgbanwe na okpomọkụ nke ngwaọrụ n'ime ahụ mmadụ.Onyonyo ọkụ na-acha ọcha gosiri na endoscope na-akpakọrịta na mucosa colonic nkịtị na vivo (Figure 3a).Enwere ike ịhụ nhụsianya nke pikselụ na-edochaghị anya n'onyinyo dị ndụ nke mucosa colonic nkịtị (Foto 3b).Mgbe a gwọchara ya na usoro kwesịrị ekwesị na mgbanwe dị iche iche, enwere ike ịmata ọdịiche nke subcellular nke mucosa (Fig 3c).Maka ozi ndị ọzọ, a na-egosi ihe oyiyi confocal raw na ihe oyiyi oge na-emepụta na Fig. S1, na nhazi nhazi ihe oyiyi eji eme ihe maka oge na nhazi oge na-egosi na Tebụl S1 na Tebụl S2.
Nhazi onyonyo.(a) Ihe onyonyo obosara nke akụkụ endoscopic na-egosi endoscope (E) etinyere na kọntaktị na mucosa nkịtị (N) colonic mucosa iji nakọta na vivo ihe onyonyo fluorescent mgbe nchịkwa fluorescein gasịrị.(b) Ịwagharị na axes X na Y n'oge nyocha nwere ike ime ka pikselụ emekọghị nke ọma.Maka ebumnuche ngosi, a na-etinye nnukwu mgbanwe oge na onyonyo izizi.(c) Mgbe emezigharị usoro nhazi post-processing, enwere ike nyochaa nkọwa nke mucosal, gụnyere akụkụ crypt (akụ), yana lumen etiti (l) nke lamina propria (lp) gbara ya gburugburu.Enwere ike ịmata otu mkpụrụ ndụ otu, gụnyere colonocytes (c), sel goblet (g), na mkpụrụ ndụ mkpali (akụ).Hụ vidiyo agbakwunyere 1. (b, c) Foto ejiri LabVIEW 2021 hazie.
Enwetara ihe onyonyo confocal fluorescence na vivo n'ọtụtụ ọrịa colonic iji gosipụta nnukwu ngwa ụlọ ọgwụ nke ngwa ahụ.A na-ebu ụzọ mee onyonyo n'obosara site na iji ọkụ ọcha chọpụta nnukwu mucosa na-adịghị mma.A na-ebuli endoscope ahụ site na ọwa ọrụ nke colonoscope ma webata ya na mucosa.
A na-egosi endoscopy nke mbara ala, confocal endomicroscopy, na histology (H & E) ihe oyiyi maka colonic neoplasia, gụnyere tubular adenoma na hyperplastic polyp. A na-egosi endoscopy nke mbara ala, confocal endomicroscopy, na histology (H & E) ihe oyiyi maka colonic neoplasia, gụnyere tubular adenoma na hyperplastic polyp. Шиrokopolnaya эndoskopyya, konphokalnaya эndomykroskopyya na gystolologic (H&E) na-agba ọsọ egwuregwu. включая тубулярную аденому na гиперпластический полип. A na-egosi endoscopy colonoscopy, confocal endomicroscopy, na ihe ngosi histological (H&E) maka neoplasia colonic, gụnyere tubular adenoma na hyperplastic polyp.显示结肠肿瘤（包括管状腺瘤和增生性息肉）的广角内窥镜检查、共聚和增生性息肉）织学(H&E) 图像.共计脚肠化(图像管状躰化和增生性息肉) &E) onyonyo. Шиrokopolnaya эndoskopyya, konphokalnaya mikroэndoskopyya na gystologycheskie (H&E) na-ezoberazhnya, pọkazyv и, включая тубулярные аденомы na гиперпластические полипы. Ọkpụkpụ endoscopy sara mbara, microendoscopy confocal, na ihe onyonyo histological (H&E) na-egosi etuto nke eriri afọ, gụnyere adenomas tubular na polyps hyperplastic.Tubular adenomas gosipụtara mfu nke ihe owuwu crypt nkịtị, mbelata nha nke mkpụrụ ndụ goblet, mgbagha nke lumen crypt, na ịgbatị lamina propria (Fig 4a-c).Hyperplastic polyps gosiri stelate architecture nke crypts, ole na ole goblet cell, slit-dị ka lumen nke crypts, na oge ụfọdụ lamellar crypts (Fig. 4d-f).
Onyonyo nke oke akpụkpọ anụ mucosal na vivo. A na-egosi ihe oyiyi endoscopy ọcha na-acha ọcha, confocal endomicroscope, na histology (H&E) onyonyo maka (ac) adenoma, (df) hyperplastic polyp, (gi) ulcerative colitis, na (jl) Crohn's colitis. A na-egosi ihe oyiyi endoscopy ọcha na-acha ọcha, confocal endomicroscope, na histology (H&E) onyonyo maka (ac) adenoma, (df) hyperplastic polyp, (gi) ulcerative colitis, na (jl) Crohn's colitis. Ndị na-eme ihe nkiri na ndị na-eme ihe nkiri na ndị na-eme ihe nkiri (H&E) , (H&E). перпластического полипа, (gi) язвенного колита и (jl) колита Крона. A na-egosipụta ihe ngosi endoscopy na-acha ọcha, confocal endomicroscope, na histology (H&E) onyonyo maka (ac) adenoma, (df) hyperplastic polyp, (gi) ulcerative colitis, na (jl) Crohn's colitis.显示了(ac) 腺瘤、(df) 增生性息肉、(gi) 溃疡性结肠炎和(jl)查、共聚焦内窥镜检查和组织学( H&E) 图像. It shows(ac) 躰真、(df) 增生性息肉、(gi) 苏盖性红肠炎和(jl)公司内肠肠炎性和电视学( H&E ) onyonyo. Ndị na-emepụta ihe na-emepụta ihe na-emepụta ihe na-emepụta ihe na-emepụta ihe na-emepụta ihe na-eme ka ọkpụkpụ na-egbuke egbuke na-egbuke egbuke (ac) , полипоза, (gi) язвенного колита и (jl) колита Крона (H&E). A na-egosi endoscopy nke ìhè ọcha, confocal endoscopy, na histology nke (ac) adenoma, (df) hyperplastic polyposis, (gi) ulcerative colitis, na (jl) Crohn's colitis (H&E).(B) na-egosi foto confocal enwetara na vivo site na adenoma tubular (TA) site na iji endoscope (E).Ọnya a na-ebute ụzọ na-egosi mfu nke ụkpụrụ crypt nkịtị (akụ), mgbagha nke crypt lumen (l), na mkpọkọta crypt lamina propria (lp).A pụkwara ịmata mkpụrụ ndụ ndị na-egbu egbu (c), sel goblet (g), na mkpụrụ ndụ mkpali (akụ).Smt.Vidiyo mgbakwunye 2. (e) na-egosi onyonyo confocal enwetara site na hyperplastic polyp (HP) na vivo.Ọnya a na-adịghị mma na-egosipụta stellate crypt architecture (akụ), slit-like crypt lumen (l), na lamina propria (lp).A na-achọpụtakwa colonocytes (c), ọtụtụ mkpụrụ ndụ goblet (g) na sel mkpali (akụ).Smt.Video mgbakwunye 3. (h) na-egosi foto confocal enwetara na ulcerative colitis (UC) na vivo.Ọnọdụ mkpasu iwe a na-egosi nrụkọba crypt architecture (akụ) na mkpụrụ ndụ goblet a ma ama (g).A na-ewepụ feathers nke fluorescein (f) site na mkpụrụ ndụ epithelial, na-egosipụta mmụba vaskụla permeability.A na-ahụ ọtụtụ mkpụrụ ndụ mkpali (akụ) na lamina propria (lp).Smt.Video mgbakwunye 4. (k) na-egosi foto confocal enwetara na vivo site na mpaghara Crohn's colitis (CC).Ọnọdụ mkpasu iwe a na-egosi nrụkọba crypt architecture (akụ) na mkpụrụ ndụ goblet a ma ama (g).A na-ewepụ feathers nke fluorescein (f) site na mkpụrụ ndụ epithelial, na-egosipụta mmụba vaskụla permeability.A na-ahụ ọtụtụ mkpụrụ ndụ mkpali (akụ) na lamina propria (lp).Smt.Vidiyo mgbakwunye 5. (b, d, h, l) onyonyo ejirila LabVIEW 2021 hazie.
E gosipụtara ihe oyiyi yiri nke ahụ nke mbufụt colon, gụnyere ulcerative colitis (UC) (Figure 4g-i) na Crohn's colitis (Figure 4j-l).A na-eche na nzaghachi mkpali ahụ bụ ihe arụrụ arụ crypt gbagọrọ agbagọ nwere mkpụrụ ndụ goblet na-apụta.A na-ewepụ Fluorescein na sel epithelial, na-egosipụta mmụba vaskụla permeability.Enwere ike ịhụ ọnụ ọgụgụ buru ibu nke mkpụrụ ndụ mkpali na lamina propria.
Anyị egosipụtala ngwa ụlọ ọgwụ nke eriri confocal laser endoscope na-agbanwe agbanwe nke na-eji nyocha MEMS edobere anya maka inweta ihe onyonyo vivo.N'oge na-agbagharị agbagharị, enwere ike nweta ọnụego etiti ruo 20 Hz site na iji usoro nyocha Lissajous dị elu iji belata arịa ngagharị.A na-apịaji ụzọ anya iji nye mgbasawanye beam na oghere ọnụọgụ zuru ezu iji nweta mkpebi mpụta nke 1.1 µm.A na-enweta ihe oyiyi na-egbuke egbuke nke àgwà akụkọ ihe mere eme n'oge colonoscopy oge niile nke mucosa colonic nkịtị, tubular adenomas, hyperplastic polyps, ulcerative colitis, na Crohn's colitis.Enwere ike ịmata otu mkpụrụ ndụ, gụnyere colonocytes, mkpụrụ ndụ goblet, na sel mkpali.Enwere ike ịmata njirimara mucosal dị ka ihe owuwu crypt, cavities crypt, na lamina propria.Akụrụngwa nkenke bụ obere igwe iji hụ na nhazi nke ọma nke ngwa anya na igwe n'otu n'otu n'ime 2.4mm dayameta x 10mm ogologo ngwa.Nhazi ngwa anya na-ebelata ogologo n'ọnụ tere aka siri ike nke ọma iji kwe ka ị gafere kpọmkwem site na nha ọkọlọtọ (dayameta 3.2 mm) na-arụ ọrụ na endoscopes ahụike.Ya mere, n'agbanyeghị onye nrụpụta, ngwaọrụ ahụ nwere ike iji ya mee ihe n'ọtụtụ ebe ndị dọkịta nọ n'ebe obibi.Emere ihe mkpali na λex = 488 nm iji kpalie fluorescein, ihe agba agba FDA kwadoro, iji nweta ọdịiche dị elu.Emegharịrị ngwaọrụ ahụ n'enweghị nsogbu maka okirikiri iri na asatọ site na iji ụzọ igba ogwu anabatara nke ụlọ ọgwụ.
Emebere ngwaọrụ abụọ ọzọ akwadoro ụlọ ọgwụ.Cellvizio (Mauna Kea Teknụzụ) bụ nyocha nke dabere na confocal laser endoscope (pCLE) nke na-eji eriri multimode coherent fiber optic cables na-anakọta na bufee foto fluorescence1.Igwe galvo dị na ọdụ ọdụ na-eme nyocha mpụta na njedebe dị nso.A na-anakọta akụkụ anya n'ụgbọ elu kwụ ọtọ (XY) nwere omimi nke 0 ruo 70 µm.Ngwa microprobe dị site na 0.91 (19G agịga) ruo 5 mm na dayameta.Emere mkpebi dị n'akụkụ 1 ruo 3.5 µm.Achịkọtara onyonyo n'ogo etiti nke 9 ruo 12 Hz nwere otu akụkụ nlele sitere na 240 ruo 600 µm.A na-eji ikpo okwu eme ihe n'ụlọ ọgwụ n'ọtụtụ ebe gụnyere bile duct, eriri afo, colon, esophagus, ngụgụ, na pancreas.Optiscan Pty Ltd ewepụtala endoscope dabere confocal laser endoscope (eCLE) nke nwere igwe nyocha nke arụnyere n'ime tube ntinye (njedebe distal) nke endoscope ọkachamara (EC-3870K, Pentax Precision Instruments) 17.A na-eme akụkụ anya anya site na iji eriri otu ụdị, a na-eme nyocha akụkụ site na iji usoro cantilever site na ndụdụ na-emegharị anya.A na-eji ihe na-eme ihe na-eme ihe na-eme ka ebe nchekwa ihe (Nitinol) mee mgbanwe axial.Ngụkọta dayameta nke modul confocal bụ 5 mm.Maka itinye uche, a na-eji oghere GRIN nwere oghere ọnụọgụ nke NA = 0.6.Enwetara onyonyo kwụ ọtọ site na mpụta na axial mkpebi nke 0.7 na 7 µm, n'otu n'otu, n'ogo etiti nke 0.8-1.6 Hz na oghere nlele nke 500 µm × 500 µm.
Anyị na-egosipụta mkpebi subcellular na vivo fluorescence inweta onyonyo site na ahụ mmadụ site na endoscopy ahụike site na iji nyocha MEMS dị anya.Fluorescence na-enye ọdịiche dị elu nke onyonyo, na njikọ ndị na-ejikọta na ebumnuche elu cell nwere ike ịkpọ ya na fluorophores iji nye njirimara molekụla maka nchọpụta ọrịa ka mma18.A na-emepụtakwa usoro anya ndị ọzọ maka vivo microendoscopy. OCT na-eji ogologo nkwekọ dị mkpụmkpụ sitere na isi iyi brọdband na-anakọta onyonyo n'ime ụgbọ elu kwụ ọtọ nwere omimi> 1 mm19. OCT na-eji ogologo nkwekọ dị mkpụmkpụ sitere na isi iyi brọdband na-anakọta onyonyo n'ime ụgbọ elu kwụ ọtọ nwere omimi> 1 mm19. ОКТ использует короткую когерентности широкополосного источника глубиной > 1 mm19. OCT na-eji ogologo nkwekọ dị mkpirikpi nke isi iyi brọdband iji nweta onyonyo n'ime ụgbọ elu kwụ ọtọ nwere>1 mm omimi19. OCT 使用宽带光源的短相干长度来收集垂直平面中深度> 1 mm19 的图像。1 mm19 的图像. ОКТ использует короткую длину когерентности альной плоскости. OCT na-eji ogologo nkwekọ dị mkpirikpi nke isi iyi brọdband nweta onyonyo>1 mm19 n'ime ụgbọ elu kwụ ọtọ.Agbanyeghị, ụzọ a dị obere na-adabere na nchịkọta ọkụ gbasasịa azụ na mkpebi onyonyo na-ejedebe site na arịa speckle.Photoacoustic endoscopy na-emepụta na onyonyo vivo dabere na mgbasawanye thermoelastic ngwa ngwa n'anụ ahụ mgbe ọ nwetasịrị usu laser nke na-ebute ụda ebili mmiri20. Usoro a egosila omimi onyonyo> 1 cm na eriri afọ mmadụ na vivo iji nyochaa ọgwụgwọ. Usoro a egosila omimi onyonyo> 1 cm na eriri afọ mmadụ na vivo iji nyochaa ọgwụgwọ. 1 см в толстой кишке человека in vivo для моитрипины . Usoro a egosila omimi ihe onyonyo> 1 cm na eriri afọ mmadụ na vivo maka nlekota ọgwụgwọ.这种方法已经证明在体内人结肠中成像深度> 1 厘米以监测治疗。这种方法已经证明在体内人结肠中成像深度> 1 Этот подход был продемонстрирован на глубине изображения > 1 см в толстой кишке человека in vivo для монитото. Egosiputara usoro a na omimi onyonyo> 1 cm na eriri mmadụ na vivo iji nyochaa ọgwụgwọ.A na-emepụta ihe dị iche iche site na haemoglobin na vasculature.Multiphoton endoscopy na-emepụta ihe oyiyi fluorescence dị elu mgbe foto abụọ NIR ma ọ bụ karịa kụrụ biomolecules anụ ahụ n'otu oge21. Usoro a nwere ike nweta omimi onyonyo> 1 mm na obere phototoxicity. Usoro a nwere ike nweta omimi onyonyo> 1 mm na obere phototoxicity. Этот подход может обеспечить глубину изображения > 1 mm с низкой фототоксичностью. Usoro a nwere ike inye omimi ihe onyonyo> 1 mm na obere fototoxicity.这种方法可以实现>1 毫米的成像深度，光毒性低。这种方法可以实现>1 毫米的成像深度，光毒性低。 Этот подход может обеспечить глубину изображения > 1 mm с низкой фототоксичностью. Usoro a nwere ike inye omimi ihe onyonyo> 1 mm na obere fototoxicity.A na-achọ pulses laser femtosecond dị elu na usoro a egosipụtabeghị na ụlọ ọgwụ n'oge endoscopy.
N'ime ihe ngosi a, nyocha na-eme naanị ntụgharị ihu, yabụ akụkụ anya dị na ụgbọ elu kwụ ọtọ (XY).Ngwaọrụ nwere ike ịrụ ọrụ n'ogo dị elu (20 Hz) karịa enyo galvanic (12 Hz) na sistemụ Cellvizio.Mee ka ọ̀tụ̀tụ̀ fekere ahụ dị elu iji belata ihe ndị na-emegharị ahụ ma belata ọnụ ọgụgụ etiti iji kwalite mgbama.Algọridim dị elu na akpaghị aka dị mkpa iji belata nnukwu ihe mmegharị ahụ nke mmegharị endoscopic kpatara, mmegharị iku ume, na motility eriri afọ.Egosiwo ihe nlebanya resonant parametric iji nweta nchụpụ axial karịrị narị narị microns22. Enwere ike ịnakọta ihe oyiyi na ụgbọ elu kwụ ọtọ (XZ), na-adabere na elu mucosal, iji nye otu echiche dị ka nke histology (H&E). Enwere ike ịnakọta ihe oyiyi na ụgbọ elu kwụ ọtọ (XZ), na-adabere na elu mucosal, iji nye otu echiche dị ka nke histology (H&E). Изображения могут быть получены в вертикальной плоскости (XZ), перпендикулярной поверхности, такое же изображение, как при гистологии (H&E). Enwere ike ịse foto na ụgbọ elu kwụ ọtọ (XZ) n'akụkụ elu mucosal iji nye otu ihe oyiyi dị na histology (H&E).可以在垂直于粘膜表面的垂直平面(XZ) 中收集图像，以提供与组织学(H&E)可以在垂直于粘膜表面的垂直平面(XZ) 中收集图像，以提供与组织学(H&E) Изображения могут быть получены в вертикальной плоскости (XZ), перпендикулярной поверхности, такое же изображение, как при гистологическом исследовании (H&E). Enwere ike ịse foto na ụgbọelu kwụ ọtọ (XZ) na-adabere na elu mucosal iji nye otu ihe oyiyi dị ka nyocha akụkọ ihe mere eme (H & E).Enwere ike idobe ihe nyocha ahụ n'ọnọdụ ebumnobi gafechara ebe ọkụ ọkụ na-adaba n'akụkụ axis ngwa anya iji belata mmetụta na aberrations8.Mpịakọta ntụsara aka kpaara ihe fọrọ nke nta ka ọ bụrụ nhụsianya nwere ike ịpụ n'okirikiri nnukwu nlele anya aka ike.Enwere ike ịme nyocha ohere ịnweta ohere iji chegharịa ndị na-atụgharị uche gaa na ọnọdụ ndị ọrụ akọwapụtara9.Enwere ike ibelata mpaghara nlele ka ọ pụta ìhè n'akụkụ ihe onyonyo a, na-emezi ọkwa mgbama na mkpọtụ, ọdịiche, na ọnụego etiti.Enwere ike imepụta nyocha nke ukwuu site na iji usoro dị mfe.Enwere ike ịme ọtụtụ narị ngwaọrụ na wafer silicon ọ bụla iji mụbaa mmepụta maka mmepụta oke ọnụ ala na nkesa sara mbara.
Ụzọ ọkụ apịaji apịaji na-ebelata nha nke isi mgbapụ siri ike, na-eme ka ọ dị mfe iji endoscope dị ka ngwa ngwa n'oge colonoscopy oge.N'ihe onyonyo a na-egosi fluorescent, enwere ike ịhụ njirimara subcellular nke mucosa iji mata ọdịiche nke adenomas tubular (precancerous) na hyperplastic polyps (benign).Nsonaazụ ndị a na-egosi na endoscopy nwere ike ibelata ọnụọgụ biopsies na-adịghị mkpa23.Enwere ike ibelata nsogbu ndị metụtara n'ozuzu ya na ịwa ahụ, enwere ike ịhazi oge nlekota oru, na nyocha nke akụkọ ihe mere eme nke obere ọnya nwere ike ibelata.Anyị na-egosikwa na vivo onyonyo nke ndị ọrịa nwere ọrịa afọ ọzịza, gụnyere ulcerative colitis (UC) na Crohn's colitis.colonoscopy ìhè na-acha ọcha na-emekarị na-enye nlele macroscopic nke elu mucosal nwere oke ikike iji nyochaa ọgwụgwọ mucosal nke ọma.Enwere ike iji endoscopy mee ihe na vivo iji nyochaa ịdị irè nke usoro ọgwụgwọ ndu dị ka ọgwụ mgbochi TNF24.Ntụle ziri ezi na vivo nwekwara ike ibelata ma ọ bụ gbochie nlọghachi ọrịa na nsogbu dịka ịwa ahụ ma melite ogo ndụ.Enwebeghị mmeghachi omume ọjọọ dị njọ na ọmụmụ ụlọ ọgwụ jikọtara ya na iji endoscopes nwere fluorescein na vivo25. Ike laser dị n'elu mucosal bụ naanị <2 mW iji belata ihe ize ndụ maka mmerụ ahụ ọkụ wee mezuo ihe FDA chọrọ maka ihe egwu na-adịghị mkpa26 kwa 21 CFR 812. Ike laser dị n'elu mucosal bụ naanị <2 mW iji belata ihe ize ndụ maka mmerụ ahụ ọkụ wee mezuo ihe FDA chọrọ maka ihe egwu na-adịghị mkpa26 kwa 21 CFR 812. Мощность лазера на поверхности слизистой оболочки была ограничена соответствовать требованиям FDA относительно незначительного риска26 согласно 21 CFR 812. Ike laser dị n'elu mucosal nwere oke na <2mW iji belata ihe ize ndụ nke mmebi ọkụ yana izute FDA chọrọ maka ihe ize ndụ na-enweghị atụ26 n'okpuru 21 CFR 812.粘膜表面的激光功率限制在<2 mW，以最大限度地降低热损伤风险，并满足FDA 21 CFR 展开要求.粘膜表面的激光功率限制在<2 mW Мощность лазера на поверхности слизистой оболочки была ограничена соответствовать требованиям FDA 21 CFR 812 относительно незначительного риска26. Ike laser dị n'elu mucosal nwere oke na <2mW iji belata ihe ize ndụ nke mmebi ọkụ yana izute FDA 21 CFR 812 chọrọ maka ihe egwu na-enweghị atụ26.
Enwere ike gbanwee nhazi nke ngwá ọrụ iji melite ogo onyonyo.Ọpụpụ pụrụ iche dị iji belata nhụsianya gburugburu, melite mkpebi onyonyo na ịbawanye anya ọrụ.Enwere ike ịdozi SIL ka ọ dakọtara nke ọma na ndezigharị nke anụ ahụ (~ 1.4) iji meziwanye njikọ ọkụ.Enwere ike ịhazigharị ugboro mbanye iji bulie akụkụ mpụta nke nyocha wee gbasaa ebe nlele onyonyo.Ị nwere ike iji ụzọ akpaghị aka wepụ okpokolo agba nke onyonyo nwere mmegharị dị egwu iji belata mmetụta a.A ga-eji usoro ụzọ gate ọnụ ụzọ ámá (FPGA) nwere nnweta data dị elu iji nye mgbazi oge zuru oke na-arụ ọrụ nke ọma.Maka ịba uru ụlọ ọgwụ ka ukwuu, ụzọ akpaghị aka ga-edozirịrị maka ngbanwe oge na ihe nrụgharị maka nkọwa onyonyo n'ezie.Enwere ike itinye nyocha nyocha nke 3-axis parametric resonant iji webata nyocha axial 22. Emepụtala ngwaọrụ ndị a iji nweta mbugharị kwụ ọtọ na-enwetụbeghị ụdị ya> 400 µm site na ịhazigharị ugboro ugboro n'usoro ọchịchị na-egosipụta agwakọta nro nro / ike ike27. Emepụtala ngwaọrụ ndị a iji nweta mbugharị kwụ ọtọ na-enwetụbeghị ụdị ya> 400 µm site na ịhazigharị ugboro ugboro n'usoro ọchịchị na-egosipụta agwakọta nro nro / ike ike27. Эty ustroystva были разработаны для достижения беспрения в режиме, который характеризуется смешанной динамикой смягчения/жесткости27. Emebere ngwaọrụ ndị a iji nweta nchụpụ kwụ ọtọ na-enwetụbeghị ụdị ya nke> 400 µm site na ịtọ ugboro ugboro n'ụdị nke agwakọtara agwakọta soft/ hard dynamics27.这些设备的开发是为了通过在具有混合软化/硬化动力学的状态下调整驱动频华整驱动频华整驱动频华整驱动频华00 µm 的垂直位移27.在 具有 混合 软化 硬化 硬化 学 为了> 400 µm 的 垂直 位移 27. Эty ustroystva были разработаны для достижения беспрения вертикальныh смещений > 400 мкм путем ежиме со смешанной кинетикой размягчения/затвердевания27. Emebere ngwaọrụ ndị a ka ọ nweta mbugharị kwụ ọtọ na-enwetụbeghị ụdị ya> 400 µm site na ịhazigharị ugboro ole na-akpalite n'ụdị nro nro/hardening kinetics agwakọta27.N'ọdịniihu, onyonyo ntụgharị kwụ ọtọ nwere ike inye aka n'ịkwapụta ọrịa kansa n'oge (T1a).Enwere ike itinye sekit sensing capacitive iji soro mmegharị nyocha wee dozie maka mgbanwe oge 28.Ndozi oge akpaaka site na iji sekit sensọ nwere ike dochie mmezi ngwa ngwa tupu eji ya.Enwere ike imezi ntụkwasị obi akụrụngwa site na iji usoro akara akara ngwaọrụ ndị a pụrụ ịdabere na ya iji mee ka ọnụ ọgụgụ okirikiri nhazi dị elu.Teknụzụ MEMS na-ekwe nkwa ime ngwa ngwa iji endoscopes maka ịhụ epithelium nke akụkụ ahụ oghere, ịchọpụta ọrịa, na ileba anya ọgwụgwọ n'ụzọ dị ntakịrị.Site na mmepe n'ihu, usoro onyonyo ọhụrụ a nwere ike ịghọ ihe ngwọta dị ọnụ ala nke a ga-eji mee ihe dị ka ihe mgbakwunye na endoscopy ahụike maka nyocha akụkọ ihe mere eme ozugbo ma nwee ike mechaa dochie nyocha ọdịnala ọdịnala.
Emere simulations Ray tracing site na iji sọftụwia opitikal design ZEMAX (ụdị 2013) iji chọpụta oke nke ngwa anya na-elekwasị anya.Usoro nhazi gụnyere mkpebi axial nso-iche, anya ọrụ = 0 µm, na ebe nlele (FOV) karịrị 250 × 250 µm2.Maka mkpali na ogologo ikuku λex = 488 nm, ejiri otu ụdị eriri (SMF) mee ihe.A na-eji okpukpu abụọ nke achromatic iji belata ọdịiche nke mkpokọta fluorescence (Njirimara 5a).Oghere ahụ na-agafe na SMF na dayameta ubi ọnọdụ nke 3.5 μm na enweghị mkpọmkpọ ebe na-agafe n'etiti onye na-atụgharị ya na dayameta oghere nke 50 μm.Jiri oghere nmikpu siri ike (hemispherical) nwere akara ntugharị dị elu (n = 2.03) iji wedata nhụsianya okirikiri nke merenụ wee hụ na kọntaktị zuru oke na elu mucosal.Optics na-elekwasị anya na-enye ngụkọta NA = 0.41, ebe NA = nsinα, n bụ ntugharị ihe ngbanwe nke anụ ahụ, α bụ akụkụ nchikota ọkụ kachasị.Mkpebi akụkụ dị iche iche na nke axial bụ 0.44 na 6.65 µm, n'otu n'otu, na-eji NA = 0.41, λ = 488 nm, na n = 1.3313.Naanị lenses dị na azụmaahịa nwere dayameta mpụta (OD) ≤ 2 mm ka a tụlere.A na-apịaji ụzọ anya anya, na ọkụ na-ahapụ SMF na-agafe na oghere etiti nke nyocha ma na-egosipụta azụ azụ site na enyo edobere (0.29 mm na dayameta).Nhazi a na-ebelata ogologo nke njedebe siri ike siri ike iji kwado n'ihu nke endoscope site na ọkọlọtọ (dayameta 3.2 mm) na-arụ ọrụ nke endoscopy ahụike.Njirimara a na-eme ka ọ dị mfe iji dị ka ngwa ngwa n'oge endoscopy.
Ntuziaka ọkụ gbakọtara na nkwakọ ngwaahịa endoscope.(a) Oghere mkpali na-apụ na OBC wee gafee oghere etiti nke nyocha.A na-agbasawanye osisi ahụ ma gosipụta ya site na enyo okirikiri edobere azụ n'ime nyocha maka ntụgharị ihu.Optics na-elekwasị anya na-enwe otu ụzọ oghere achromatic doublet na oghere imikpu siri ike (hemispherical) na-enye kọntaktị na elu mucosal.ZEMAX 2013 (https://www.zemax.com/) maka imewe anya na simulation ray.(b) Na-egosi ọnọdụ nke akụrụngwa akụrụngwa dị iche iche, gụnyere fiber mode fiber (SMF), nyocha, enyo, na anya m.Ejiri Solidworks 2016 (https://www.solidworks.com/) maka ịmegharị 3D nke ngwugwu endoscope.
A na-eji SMF (#460HP, Thorlabs) nwere dayameta ubi ọnọdụ nke 3.5 µm n'ogo wavelength nke 488 nm dị ka "oghere" maka nzacha oghere nke ìhè debere anya (Fig 5b).A na-agbanye SMF na tubes polymer na-agbanwe agbanwe (#Pebax 72D, Nordson MEDICAL).A na-eji ogologo ihe dịka mita anọ iji hụ na anya zuru oke n'etiti onye ọrịa na usoro onyonyo.Otu ụzọ 2 mm MgF2 mkpuchi achromatic doublet lenses (#65568, #65567, Edmund Optics) na oghere hemispherical nke 2 mm na-enweghị mkpuchi (#90858, Edmund Optics) ka ejiri lekwasị anya na beam wee nakọta fluorescence.Fanye eriri ngwụcha igwe anaghị agba nchara (4 mm ogologo, 2.0 mm OD, 1.6 mm ID) n'etiti resin na tube dị n'èzí iji kewapụ ịma jijiji nyocha.Jiri nrapado ahụike iji kpuchido ngwa ahụ site na mmiri ara na usoro njikwa.Jiri tubing na-ebelata okpomọkụ iji chebe njikọ.
A na-eme nyocha kọmpat na ụkpụrụ nke resonance parametric.Tinye oghere 50 µm n'etiti ihe nlegharị anya iji bunye ọkụ na-akpali akpali.N'iji otu draịva na-ebugharị quadrature, a na-atụgharị beam ahụ gbasaa n'ụzọ ntụgharị n'ụzọ ọ bụla (ụgbọelu XY) na ọnọdụ Lissajous.A na-eji bọọdụ nnweta data (#DAQ PCI-6115, NI) wepụta akara analọgụ iji jikwaa nyocha.Enyere ike site na igwe ọkụ ọkụ dị elu (#PDm200, PiezoDrive) site na waya dị mkpa (#B4421241, MWS Wire Industries).Mee wiring na armature electrode.Ihe nyocha ahụ na-arụ ọrụ n'oge dị nso 15 kHz (axis ngwa ngwa) na 4 kHz (obere axis) iji nweta FOV ruo 250 µm × 250 µm.Enwere ike gbaa vidiyo n'ogo etiti nke 10, 16, ma ọ bụ 20 Hz.A na-eji ọnụego etiti ndị a dabara na nkwughachi nke ụkpụrụ nyocha Lissajous, nke dabere na uru nke ugboro mkpali X na Y nke scanner29.Nkọwapụta nke azụmaahịa dị n'etiti ọnụego etiti, mkpebi pikselụ, na njupụta usoro nyocha ka ewepụtara n'ọrụ anyị gara aga14.
Laser steeti siri ike (#OBIS 488 LS, coherent) na-enye λex = 488 nm iji kpalie fluorescein maka ọdịiche oyiyi (Fig 6a).Ejikọtara pigtails anya na igwe nzacha site na njikọ FC/APC (ọnwụ 1.82 dB) (Fig 6b).A na-atụgharị ọkụ ahụ site na enyo dichroic (#WDM-12P-111-488/500:600, Oz Optics) na SMF site na njikọ FC/APC ọzọ.N'ikwekọ na 21 CFR 812, ike mberede na anụ ahụ nwere oke na 2mW iji zute ihe FDA chọrọ maka ihe egwu na-enweghị atụ.A na-agafe fluorescence site na enyo dichroic na nzacha nnyefe ogologo (#BLP01-488R, Semrock).A na-ebunye fluorescence na ihe nchọpụta fotomultiplier tube (PMT) (#H7422-40, Hamamatsu) site na njikọ FC/PC na-eji ~ 1 m ogologo multimode fiber nwere dayameta 50 µm.Ejiri igwe na-agba ọsọ dị ugbu a kwalite akara fluorescent (#59-179, Edmund Optics).Ewupụtala sọftụwia pụrụ iche (LabVIEW 2021, NI) maka inweta data ozugbo yana nhazi onyonyo.A na-ekpebi ike laser na ntọala uru PMT site na microcontroller (#Arduino UNO, Arduino) na-eji bọọdụ sekit ebipụtara pụrụ iche.SMF na wires na-akwụsị na njikọ na jikọọ na eriri optic (F) na wired (W) ọdụ ụgbọ mmiri na isi ọdụ (Njirimara 6c).Usoro onyonyo dị n'ime ụgbọ ala enwere ike ibugharị (Foto 6d). A na-eji ihe ngbanwe dịpụrụ adịpụ wee kpachie ntapu nke ugbu a ka ọ bụrụ <500 μA. A na-eji ihe ngbanwe dịpụrụ adịpụ wee kpachie ntapu nke ugbu a ka ọ bụrụ <500 μA. Для ограничения тока утечки до <500 мкА использовался изолирующий трансформатор. A na-eji ihe ngbanwe dịpụrụ adịpụ wee kpachie ntapu nke ugbu a ka ọ bụrụ <500 µA.使用隔离变压器将泄漏电流限制在<500 μA。 <500 μA. Используйте изолирующий трансформатор, чтобы ограничить ток утечки до <500 мкА. Jiri ihe ngbanwe dịpụrụ adịpụ machilata ntapu ugbu a ka ọ bụrụ <500µA.
usoro ihe nlere anya.(a) PMT, laser na amplifier dị n'ọdụ ọdụ.(b) N'ime ụlọ akụ nzacha, laser (acha anụnụ anụnụ) na-anya n'elu eriri fiber optic site na njikọ FC/APC.A na-eji enyo dichroic (DM) tụgharị ọkụ ahụ n'ime otu eriri mode (SMF) site na njikọ FC/APC nke abụọ.Fluorescence (green) na-aga site na DM na ogologo ngafe nzacha (LPF) na PMT site na multimode fiber (MMF).(c) A na-ejikọta njedebe dị nso nke endoscope na eriri optic (F) na wired (W) nke ọdụ ụgbọ mmiri.(d) Endoscope, nleba anya, ọdụ ọdụ, kọmpụta, na ngbanwe dịpụrụ adịpụ na ụgbọ ala enwere ike ibugharị.(a, c) A na-eji Solidworks 2016 mee ihe maka imepụta ihe ngosi 3D nke sistemu onyonyo yana akụkụ endoscope.
A tụrụ n'akụkụ na axial mkpebi nke optics na-elekwasị anya site na ọrụ mgbasa nke fluorescent microspheres (#F8803, Thermo Fisher Scientific) 0.1µm na dayameta.Chịkọta onyonyo site na ịtụgharị microspheres kwụ n'ahịrị na kwụ ọtọ n'usoro 1µm site na iji usoro ahịrị (# M-562-XYZ, DM-13, Newport).Nchịkọta onyonyo site na iji ImageJ2 iji nweta onyonyo akụkụ nke microspheres.
Ewupụtala sọftụwia pụrụ iche (LabVIEW 2021, NI) maka inweta data ozugbo yana nhazi onyonyo.Na fig.7 na-egosi nchịkọta nke usoro a na-eji arụ ọrụ usoro.Ihe interface onye ọrụ nwere nnweta data (DAQ), isi panel na panel njikwa.Ogwe nchịkọta data na-emekọrịta ihe na isi panel iji nakọta ma chekwaa data raw, nye ntinye maka ntọala nchịkọta data omenala, na jikwaa ntọala ndị ọkwọ ụgbọ ala nyocha.Ogwe isi na-enye onye ọrụ ohere ịhọrọ nhazi achọrọ maka iji endoscope, gụnyere akara njikwa nyocha, ọnụego etiti vidiyo, na ihe nnweta.Ogwe a na-enyekwa onye ọrụ ohere igosipụta ma jikwaa nchapụta na ọdịiche nke onyinyo ahụ.N'iji data raw dị ka ntinye, algọridim na-agbakọ ntọala uru kacha mma maka PMT ma na-edozi oke a na-akpaghị aka site na iji usoro njikwa nzaghachi nha anya (PI) 16.Ndị na-ahụ maka njikwa na-emekọrịta ihe na bọọdụ isi na bọọdụ nnweta data iji chịkwaa ike laser na uru PMT.
Nhazi ngwanrọ sistemụ.Ihe interface onye ọrụ nwere modul (1) nnweta data (DAQ), (2) isi panel na (3) panel njikwa.Mmemme ndị a na-agba ọsọ n'otu oge ma na-ekwurịta okwu n'etiti ibe ha site na ahịrị ozi.Igodo bụ MEMS: Microelectromechanical System, TDMS: Nka na ụzụ njikwa data, PI: Proportal Integral, PMT: Photomultiplier.A na-echekwa faịlụ onyonyo na vidiyo n'ụdị BMP na AVI, n'otu n'otu.
A na-eji algọridim mmezi nke usoro iji gbakọọ mgbasa nke pikselụ ihe onyonyo n'ụkpụrụ dị iche iche iji chọpụta uru kacha eji eme ka onyonyo a dị nkọ.Maka mgbazi ozugbo, usoro nyocha nke usoro bụ ± 2.86° yana nzọụkwụ buru ibu nke 0.286° iji belata oge ngụkọ.Na mgbakwunye, iji akụkụ nke onyonyo a nwere obere nlele na-ebelata oge ngụkọ ihe onyonyo site na 7.5 sekọnd (1 Msample) ruo 1.88 sekọnd (250 Ksample) na 10 Hz.Ahọpụtara oke ntinye ndị a iji nye ogo onyonyo zuru oke yana obere latency n'oge onyonyo vivo.A na-edekọ onyonyo na vidiyo dị ndụ n'ụdị BMP na AVI, n'otu n'otu.A na-echekwa data raw ahụ n'ụdị usoro njikwa data teknụzụ (TMDS).
Post-processing nke in vivo onyogho maka mma mma na LabVIEW 2021. Nzizi nwere oke mgbe ị na-eji usoro mmezi algọridim n'oge in vivo imaging n'ihi ogologo oge mgbako chọrọ.Naanị mpaghara onyonyo nwere oke na ọnụọgụ nlele ka a na-eji.Na mgbakwunye, algọridim anaghị arụ ọrụ nke ọma maka onyonyo nwere arịa ngagharị ma ọ bụ ọdịiche dị ala ma na-eduga na njehie ngụkọta oge30.Ejiri aka họrọ okpokolo agba nke ọ bụla nwere nnukwu ọdịiche na enweghị ihe ọ bụla na-emegharị ahụ maka nlegharị anya nke ọma yana oke nyocha nke ± 0.75° na usoro 0.01°.A na-eji mpaghara onyonyo niile (dịka ọmụmaatụ, 1 Ihe onyonyo edekọrọ na 10 Hz).Tebụlụ S2 na-akọwapụta paramita onyonyo ejiri maka ezigbo oge yana nhazi oge.Mgbe emezigharị usoro, a na-eji ihe nzacha etiti na-ebelata mkpọtụ onyonyo n'ihu.A na-emewanye nchapụta na ọdịiche site na ịgbatị histogram na ndozi gamma31.
Ndị Michigan Medical Institutions Review Board kwadoro ule ụlọ ọgwụ ahụ ma mee ya na Ngalaba Usoro Ọgwụ.Edebara aha ọmụmụ a n'ịntanetị na ClinicalTrials.gov (NCT03220711, ụbọchị ndebanye aha: 07/18/2017).Usoro nsonye gụnyere ndị ọrịa (ndị dị afọ 18 ruo 100) nwere nhazi colonoscopy nke a na-emebu atụmatụ, ihe ize ndụ dị ukwuu nke ọrịa cancer colorectal, na akụkọ ihe mere eme nke ọrịa obi na-egbuke egbuke.Enwetara nkwenye ọmụma sitere na isiokwu ọ bụla kwetara isonye.Usoro mwepu bụ ndị ọrịa dị ime, nwere amaara hypersensitivity na fluorescein, ma ọ bụ na-enweta ọgwụgwọ chemotherapy ma ọ bụ ọgwụgwọ radieshon.Ọmụmụ ihe a gụnyere ndị ọrịa na-esochi anya nke a na-ahazi maka colonoscopy na-emekarị ma bụrụ onye nnọchiteanya nke Michigan Medical Center bi.Emere ọmụmụ ihe a dịka nkwupụta Helsinki siri dị.
Tupu ịwa ahụ, megharịa endoscope site na iji 10 µm fluorescent beads (#F8836, Thermo Fisher Scientific) nke etinyere n'ụdị silicone.Awụsara ihe mkpuchi silicone translucent (#RTV108, Momentive) n'ime ihe eji emepụta plastik 8 cm3 3D ebipụtara.Tụfuo beads mmiri fluorescent n'elu silicone wee pụọ ruo mgbe ọkara mmiri ga-akpọnwụ.
A na-enyocha eriri afọ ahụ niile site na iji ọkọlọtọ ọgwụ colonoscope (Olympus, CF-HQ190L) nwere ọkụ na-acha ọcha.Mgbe endoscopist kpebisiri ike na mpaghara ọrịa a na-ebo ebubo, a na-asacha ebe ahụ na 5-10 ml nke 5% acetic acid, wee jiri mmiri na-adịghị mma wepụ imi na irighiri ihe.A na-agbanye ọgwụ 5 ml nke 5 mg / ml fluorescein (Alcon, Fluorescite) n'ime intravenously ma ọ bụ fesa ya n'elu mucosa site na iji cannula ọkọlọtọ (M00530860, Boston Scientific) nke gafere site na ọwa ọrụ.
Jiri mmiri mmiri na-ekpochapụ ihe nfe ma ọ bụ ihe mkpofu n'elu mucosal.Wepu catheter nebulizing ma gafere endscope site na ọwa na-arụ ọrụ iji nweta onyonyo anwụ anwụ.Jiri ntụzịaka endoscopic nke mbara obosara iji dobe ọnụ ọnụ dị anya na mpaghara ebumnuche. Ngụkọta oge ejiri na-anakọta onyonyo confocal bụ <10 min. Ngụkọta oge ejiri na-anakọta onyonyo confocal bụ <10 min. Общее время, затраченое на сбор конфокальных изображений, составило <10 мин. Ngụkọta oge ewepụtara iji nakọta onyonyo confocal bụ <10 min.Ngụkọta oge nnweta maka onyonyo confocal erughị nkeji iri.Ejiri usoro onyonyo Olympus EVIS EXERA III (CLV-190) hazie vidiyo na-acha ọcha Endoscopic wee dekọọ site na iji ihe ndekọ vidiyo Elgato HD.Jiri LabVIEW 2021 ka ịdekọ na chekwaa vidiyo endoscopy.Mgbe ihe onyonyo mechara, a ga-ewepụ endoscopy wee wepụ anụ ahụ a ga-ahụ anya site na iji biopsy forceps ma ọ bụ ọnyà. A na-ahazi anụ ahụ maka akụkọ ihe mere eme oge niile (H&E), onye ọkachamara GI pathologist (HDA) nyochara ya. A na-ahazi anụ ahụ maka akụkọ ihe mere eme oge niile (H&E), onye ọkachamara GI pathologist (HDA) nyochara ya. Ткани были obrabotanы dlya obыchnoy GIstolgy (H&E) na otsenenы эkspertom-patologom zheludochno-kyshechHD. A na-ahazi anụ ahụ maka akụkọ ihe mere eme oge niile (H&E) ma nyochaa ya site n'aka ọkachamara n'ọrịa eriri afọ (HDA).对组织进行常规组织学(H&E) 处理，并由专家GI 病理学家(HDA) 进行评估。对组织进行常规组织学(H&E) 处理，并由专家GI 病理学家(HDA) 进行评估。 Ткани были obrabotanы dlya obыchnoy GIstolgy (H&E) na otsenenы эkspertom-patologom zheludochno-kyshechHD. A na-ahazi anụ ahụ maka akụkọ ihe mere eme oge niile (H&E) ma nyochaa ya site n'aka ọkachamara n'ọrịa eriri afọ (HDA).Eji spectrometer (USB2000+, Ocean Optics) kwadoro njirimara nke fluorescein dị ka egosiri na Figure S2.
A na-eme ọgwụ Endoscopes mgbe mmadụ jiri ya mee ihe (Fig 8).Emere usoro nhicha dị n'okpuru nduzi na nkwado nke Ngalaba Nchịkwa Ọrịa na Epidemiology nke Michigan Medical Center na Central Sterile Processing Unit. Tupu ọmụmụ ihe ahụ, a nwalere ngwa ndị ahụ ma kwado ya maka ịgba ọgwụ mgbochi ọrịa site na Advanced Sterilisation Products (ASP, Johnson & Johnson), ụlọ ọrụ azụmahịa na-enye mgbochi ọrịa na ọrụ nkwado igba ogwu. Tupu ọmụmụ ihe ahụ, a nwalere ngwa ndị ahụ ma kwado ya maka ịgba ọgwụ mgbochi ọrịa site na Advanced Sterilisation Products (ASP, Johnson & Johnson), ụlọ ọrụ azụmahịa na-enye mgbochi ọrịa na ọrụ nkwado igba ogwu. Перед исследованием инструменты были протестированы и одобрены для стерилизаци компанией Advanced Sterilization Products & Johnson ией, предоставляющей услуги по пофилактике инфекций na проверке стерилизации. Tupu ọmụmụ ihe, a nwalere ngwa ma kwado maka igba ogwu site na Advanced Sterilization Products (ASP, Johnson & Johnson), ụlọ ọrụ azụmahịa na-enye ọrụ mgbochi ọrịa na nyocha nyocha. Ngwaahịa Advanced Sterilisation Products (ASP, Johnson & Johnson), услуги по профилактике инфекций и проверке стерилизации. A gbanyụrụ ngwa ma nyochaa ngwa ngwa tupu Advanced Sterilisation Products (ASP, Johnson & Johnson) amụ ya, ụlọ ọrụ azụmahịa na-enye ọrụ mgbochi ọrịa na nyocha ọgwụ.
Nrụgharị akụrụngwa.(a) A na-etinye endoscopes n'ime trays ka emechara ọgwụ mgbochi ọ bụla site na iji usoro nhazi STERRAD.(b) A na-ejedebe SMF na wires na eriri optic na njikọ eletriki, n'otu n'otu, nke na-emechi tupu emegharịa ya.
Hichaa endoscopes site n'ime ihe ndị a: (1) hichaa endoscope na akwa na-enweghị lint nke etinyere na ihe nchacha enzymatic site na nso ruo n'ebe dị anya;(2) Na-emikpu ngwá ọrụ na ngwọta enzymatic detergent maka nkeji 3 na mmiri.ákwà na-enweghị lint.A na-ekpuchi njikọ eletrik na fiber optic ma wepụ ya na ngwọta;(3) A na-ekechi endoscope ma tinye ya na tray ngwá ọrụ maka igba ogwu site na iji STERRAD 100NX, hydrogen peroxide gas plasma.dịtụ ala okpomọkụ na ala iru mmiri gburugburu.
Ihe ndekọ data ejiri na/ma ọ bụ nyochaa n'ime ọmụmụ ihe ugbu a dị site n'aka ndị edemede dị iche iche na arịrịọ ezi uche dị na ya.
Pilonis, ND, Januszewicz, W. & di Pietro, M. Confocal laser endomicroscopy na gastro-intestinal endoscopy: Akụkụ nkà na ụzụ na ngwa ụlọ ọgwụ. Pilonis, ND, Januszewicz, W. & di Pietro, M. Confocal laser endomicroscopy na gastro-intestinal endoscopy: Akụkụ nkà na ụzụ na ngwa ụlọ ọgwụ.Pilonis, ND, Januszewicz, V. i di Pietro, M. Confocal laser endoscopy na eriri afọ endoscopy: akụkụ teknụzụ na ngwa ụlọ ọgwụ. Pilonis, ND, Januszewicz, W. & di Pietro, M. 胃肠内窥镜检查中的共聚焦激光内窥镜检查：技术方鸢咨和却咨 Pilonis, ND, Januszewicz, W. & di Pietro, M. 共载肠分别在在共公司设计在机机： Akụkụ nka na ngwa ụlọ ọgwụ.Pilonis, ND, Januszewicz, V. i di Pietro, M. Confocal laser endoscopy na eriri afọ endoscopy: akụkụ teknụzụ na ngwa ụlọ ọgwụ.nsụgharị heparin eriri afọ.7, 7 (2022).
Al-Mansour, MR et al.Nyocha nchekwa na arụmọrụ nke SAGES TAVAC Confocal Laser Endomicroscope.Ọrụ.Endoscopy 35, 2091-2103 (2021).
Fugazza, A. et al.Confocal laser endoscopy na ọrịa eriri afọ na ọrịa pancreatobiliary: nyocha usoro na meta-analysis.Sayensị biomedical.tankị nchekwa.ime 2016, 4638683 (2016).