Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis
The early-stage diagnosis of cancer is a crucial clinical need. The inadequacies of surgery tissue biopsy have prompted a transition to a less invasive profiling of molecular biomarkers from biofluids, known as liquid biopsy. Exosomes are phospholipid bilayer vesicles present in many biofluids with...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2023-11-01
|
Series: | Sensors |
Subjects: | |
Online Access: | https://www.mdpi.com/1424-8220/23/23/9432 |
_version_ | 1797399589926469632 |
---|---|
author | Valentina Marassi Stefano Giordani Anna Placci Angela Punzo Cristiana Caliceti Andrea Zattoni Pierluigi Reschiglian Barbara Roda Aldo Roda |
author_facet | Valentina Marassi Stefano Giordani Anna Placci Angela Punzo Cristiana Caliceti Andrea Zattoni Pierluigi Reschiglian Barbara Roda Aldo Roda |
author_sort | Valentina Marassi |
collection | DOAJ |
description | The early-stage diagnosis of cancer is a crucial clinical need. The inadequacies of surgery tissue biopsy have prompted a transition to a less invasive profiling of molecular biomarkers from biofluids, known as liquid biopsy. Exosomes are phospholipid bilayer vesicles present in many biofluids with a biologically active cargo, being responsible for cell-to-cell communication in biological systems. An increase in their excretion and changes in their cargo are potential diagnostic biomarkers for an array of diseases, including cancer, and they constitute a promising analyte for liquid biopsy. The number of exosomes released, the morphological properties, the membrane composition, and their content are highly related to the physiological and pathological states. The main analytical challenge to establishing liquid biopsy in clinical practice is the development of biosensors able to detect intact exosomes concentration and simultaneously analyze specific membrane biomarkers and those contained in their cargo. Before analysis, exosomes also need to be isolated from biological fluids. Microfluidic systems can address several issues present in conventional methods (i.e., ultracentrifugation, size-exclusion chromatography, ultrafiltration, and immunoaffinity capture), which are time-consuming and require a relatively high amount of sample; in addition, they can be easily integrated with biosensing systems. A critical review of emerging microfluidic-based devices for integrated biosensing approaches and following the major analytical need for accurate diagnostics is presented here. The design of a new miniaturized biosensing system is also reported. A device based on hollow-fiber flow field-flow fractionation followed by luminescence-based immunoassay is applied to isolate intact exosomes and characterize their cargo as a proof of concept for colon cancer diagnosis. |
first_indexed | 2024-03-09T01:43:17Z |
format | Article |
id | doaj.art-a558a1ce31ff48108d9e5768f45830c3 |
institution | Directory Open Access Journal |
issn | 1424-8220 |
language | English |
last_indexed | 2024-03-09T01:43:17Z |
publishDate | 2023-11-01 |
publisher | MDPI AG |
record_format | Article |
series | Sensors |
spelling | doaj.art-a558a1ce31ff48108d9e5768f45830c32023-12-08T15:25:58ZengMDPI AGSensors1424-82202023-11-012323943210.3390/s23239432Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer DiagnosisValentina Marassi0Stefano Giordani1Anna Placci2Angela Punzo3Cristiana Caliceti4Andrea Zattoni5Pierluigi Reschiglian6Barbara Roda7Aldo Roda8Department of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyNational Institute of Biostructure and Biosystems (INBB), 00136 Rome, ItalyNational Institute of Biostructure and Biosystems (INBB), 00136 Rome, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyDepartment of Chemistry “G. Ciamician”, University of Bologna, 40126 Bologna, ItalyThe early-stage diagnosis of cancer is a crucial clinical need. The inadequacies of surgery tissue biopsy have prompted a transition to a less invasive profiling of molecular biomarkers from biofluids, known as liquid biopsy. Exosomes are phospholipid bilayer vesicles present in many biofluids with a biologically active cargo, being responsible for cell-to-cell communication in biological systems. An increase in their excretion and changes in their cargo are potential diagnostic biomarkers for an array of diseases, including cancer, and they constitute a promising analyte for liquid biopsy. The number of exosomes released, the morphological properties, the membrane composition, and their content are highly related to the physiological and pathological states. The main analytical challenge to establishing liquid biopsy in clinical practice is the development of biosensors able to detect intact exosomes concentration and simultaneously analyze specific membrane biomarkers and those contained in their cargo. Before analysis, exosomes also need to be isolated from biological fluids. Microfluidic systems can address several issues present in conventional methods (i.e., ultracentrifugation, size-exclusion chromatography, ultrafiltration, and immunoaffinity capture), which are time-consuming and require a relatively high amount of sample; in addition, they can be easily integrated with biosensing systems. A critical review of emerging microfluidic-based devices for integrated biosensing approaches and following the major analytical need for accurate diagnostics is presented here. The design of a new miniaturized biosensing system is also reported. A device based on hollow-fiber flow field-flow fractionation followed by luminescence-based immunoassay is applied to isolate intact exosomes and characterize their cargo as a proof of concept for colon cancer diagnosis.https://www.mdpi.com/1424-8220/23/23/9432liquid biopsyexosomescolon cancermicrofluidicreagent less biosensorshollow-fiber field-flow fractionation |
spellingShingle | Valentina Marassi Stefano Giordani Anna Placci Angela Punzo Cristiana Caliceti Andrea Zattoni Pierluigi Reschiglian Barbara Roda Aldo Roda Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis Sensors liquid biopsy exosomes colon cancer microfluidic reagent less biosensors hollow-fiber field-flow fractionation |
title | Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis |
title_full | Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis |
title_fullStr | Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis |
title_full_unstemmed | Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis |
title_short | Emerging Microfluidic Tools for Simultaneous Exosomes and Cargo Biosensing in Liquid Biopsy: New Integrated Miniaturized FFF-Assisted Approach for Colon Cancer Diagnosis |
title_sort | emerging microfluidic tools for simultaneous exosomes and cargo biosensing in liquid biopsy new integrated miniaturized fff assisted approach for colon cancer diagnosis |
topic | liquid biopsy exosomes colon cancer microfluidic reagent less biosensors hollow-fiber field-flow fractionation |
url | https://www.mdpi.com/1424-8220/23/23/9432 |
work_keys_str_mv | AT valentinamarassi emergingmicrofluidictoolsforsimultaneousexosomesandcargobiosensinginliquidbiopsynewintegratedminiaturizedfffassistedapproachforcoloncancerdiagnosis AT stefanogiordani emergingmicrofluidictoolsforsimultaneousexosomesandcargobiosensinginliquidbiopsynewintegratedminiaturizedfffassistedapproachforcoloncancerdiagnosis AT annaplacci emergingmicrofluidictoolsforsimultaneousexosomesandcargobiosensinginliquidbiopsynewintegratedminiaturizedfffassistedapproachforcoloncancerdiagnosis AT angelapunzo emergingmicrofluidictoolsforsimultaneousexosomesandcargobiosensinginliquidbiopsynewintegratedminiaturizedfffassistedapproachforcoloncancerdiagnosis AT cristianacaliceti emergingmicrofluidictoolsforsimultaneousexosomesandcargobiosensinginliquidbiopsynewintegratedminiaturizedfffassistedapproachforcoloncancerdiagnosis AT andreazattoni emergingmicrofluidictoolsforsimultaneousexosomesandcargobiosensinginliquidbiopsynewintegratedminiaturizedfffassistedapproachforcoloncancerdiagnosis AT pierluigireschiglian emergingmicrofluidictoolsforsimultaneousexosomesandcargobiosensinginliquidbiopsynewintegratedminiaturizedfffassistedapproachforcoloncancerdiagnosis AT barbararoda emergingmicrofluidictoolsforsimultaneousexosomesandcargobiosensinginliquidbiopsynewintegratedminiaturizedfffassistedapproachforcoloncancerdiagnosis AT aldoroda emergingmicrofluidictoolsforsimultaneousexosomesandcargobiosensinginliquidbiopsynewintegratedminiaturizedfffassistedapproachforcoloncancerdiagnosis |