Abstract

Circulating tumor cells (CTCs), a type of cancer cell that spreads from primary tumors into human peripheral blood and are considered as a new biomarker of cancer liquid biopsy. It provides the direction for understanding the biology of cancer metastasis and progression. Isolation and analysis of CTCs offer the possibility for early cancer detection and dynamic prognosis monitoring. The extremely low quantity and high heterogeneity of CTCs are the major challenges for the application of CTCs in liquid biopsy. There have been significant research endeavors to develop efficient and reliable approaches to CTC isolation and analysis in the past few decades. With the advancement of microfabrication and nanomaterials, a variety of approaches have now emerged for CTC isolation and analysis on microfluidic platforms combined with nanotechnology. These new approaches show advantages in terms of cell capture efficiency, purity, detection sensitivity and specificity. This review focuses on recent progress in the field of nanotechnology-assisted microfluidics for CTC isolation and detection. Firstly, CTC isolation approaches using nanomaterial-based microfluidic devices are summarized and discussed. The different strategies for CTC release from the devices are specifically outlined. In addition, existing nanotechnology-assisted methods for CTC downstream analysis are summarized. Some perspectives are discussed on the challenges of current methods for CTC studies and promising research directions.

Highlights

  • Cancer has become one of the leading causes of death worldwide, and tumor metastasis is the main cause of high cancer mortality [1]

  • A capture yield of more than 95% of the MCF-7 cell line from artificial blood samples was achieved at an optimal flow rate of 1.0 mL h−1

  • Each method has respective strengths and weaknesses depending on the downstream application

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Summary

Introduction

Cancer has become one of the leading causes of death worldwide, and tumor metastasis is the main cause of high cancer mortality [1]. A microfluidic device has the features of miniaturization, portability, cost-effectiveness and precise control of the localized microenvironment, which caused it to become one of the mainstream technologies for CTC study [5,8] These reports either focused on the different methodologies of CTC isolation based on their physical properties [21,22,23,24,25,26,27,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51] or CTC detection using microfluidic devices based on the newly discovered CTC biomarkers and their affinity reaction. CCTTCCisiosolaltaitoinonexepxploliotsitsthtehedidffiffereernecnecsesininphpyhsyisciaclaal nadnd bbiochemical pproropperetriteiessbebtweteweeneCn TCCTsCans dahnedmahteompaotioetpicoiceetlilcs. cMelilcsr.oflMuiicdroicflcuhiidpictechnipolotegcyhpnroolovgidyes ipmropvleidmeesnitmatpiolenmceonntadtiitoionncsonfodritinontesgrfoartiningtemgrualttiinpglemoupletirpalteioonps,eriantciolunds,inigncplurdetinregatpmreetnrte,atcmapetnut,re, dcaeptetcutrieo,n,deetce.c,tinotno, aetsci.n, gilnetomiacrosindgelveicme,itchrousdpervoivceid, itnhguas cpornovveidninengt aplacotfnovrmenifeonrtsupblastefqorumentfocrell rseusbesaerqchu.enTtaicleolrlirnegsetahrechn.aTnaoisltorruinctgutrheeonf athneosmtriucrcotuflrueidoficthdeevmicicercoaflnupidriocvdideveiscuercfanceparroevaisdfeosruarffifanceity laigreaansdfoimr amffoinbiitlyizlaitgiaonndanimdm/oor bmiloizdautiloanteaflnudi/doircmflowduclahtaeraflcutiedricstfilcoswtocehnahraacntceeristhtiecseffitoceinenhcayncoef tChTeC ceaffpictuierne.cyForf tChTeCpocastp-tpurroec.eFsosirntgheanpaolsyts-ipsr,othceescsainpgtuarneadlyCsTisC, tshsehcoaupldturreemd aCinTCvsiasbhloeualnddrebme raeinleavsiaebdlefor saunbdsebqeureenlet aasneadlyfsoirs.sNuboswe,qiuteins timanpaolrytsains.t Ntooewxp, liot ries riemaspoonrtaabnlet tcoapetxuprleoarendreraesloenasaeblpelactafportumrse uannder trheelenasaenoptleacthfonromlosguyn-adsesristtheed nmaincoroteflcuhindoiclosgtrya-atesgsiystteodremailcizreofeluffiidciecnsttraantdeghyigtho-preuarlitzyeseefpfiacriaentitonanadnd ohvigehrc-opmureittyhseepadarhaetsioivneafnodrcoevsewrchoimleekteheepaindghecseilvlse vfoiarcbeles wanhdileuknepeepritnugrbceedll.s viable and unperturbed

22.1. Physical anndd BBiioocchheemmiiccaallPPrrooppeerrttiieessooffCCTTCCss
Nanotechnology-Assisted CTC Capture
Nanoparticles in Suspensions for CTC Capture
Nanostructures on Substrates for CTC Capture
Enzymatic Degradation-Based CTC Release
Light-Controlled CTC Release
Electrochemical and Chemical Reagent-Triggered CTC Release
Ligand Competition for CTC Release
Nanotechnology-Assisted CTC Analysis in Microfluidic Chips
CTC Morphologic Analysis
CTC Genomic Analysis
CTC Transcriptomic Profiling
CTC Protein Analysis
Findings
Conclusions
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