Whole blood analysis using microfluidic plasma separation and enzyme-linked immunosorbent assay devices

Shimizu, Hisashi; Kumagai, Mariko; Mori, Emi; Mawatari, Kazuma; Kitamori, Takehiko

doi:10.1039/c6ay01779g

Cited by 11 publications

(5 citation statements)

References 36 publications

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“…There have been multiple reports of standalone microfluidic plasma separation systems. − For example, Homsy et al reported the isolation of 12 μL of plasma from 100 μL of whole blood within 7 min . Several other reports described microfluidic devices integrating plasma separation with downstream analyses. − For example, Yeh et al separated plasma and carried out on-chip nucleic acid amplification for the detection of HIV-1 RNA and Staphylococcus aureus DNA spiked in whole blood . Another paper described a microfluidic immunoassay for the detection of C-reactive protein performed downstream of plasma separation .…”

Section: Introductionmentioning

confidence: 99%

Automated Microfluidic System with Active Mixing Enables Rapid Analysis of Biomarkers in 5 μL of Whole Blood

et al. 2022

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We developed a microfluidic device for the rapid analysis of biomarkers in small volumes of whole blood. This device includes an onboard plasma separation module connected to a downstream bioanalysis module in which plasma mixes with reagents and the results of a colorimetric assay are recorded. Actuation of onboard microvalves within a bioanalysis module creates active mixing conditions that allowed us to achieve solution homogeneity within 5 min. To demonstrate utility, we carried out glucose detection in our device. With 5 μL of whole blood as an input, our microfluidic device enabled a time-to-answer of 10 min with a limit of detection of 0.21 ± 0.04 mM for glucose. This device has immediate applications for rapid and sensitive monitoring of hypoglycemia at the point of care (POC). Furthermore, our automated microfluidic device represents a platform technology that may be used to detect other biomarkers in whole blood.

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Section: Introductionmentioning

confidence: 99%

Automated Microfluidic System with Active Mixing Enables Rapid Analysis of Biomarkers in 5 μL of Whole Blood

et al. 2022

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“…Traditionally, a bio-fluid separation has been performed by centrifugation or chromatography. Recently, there has been technological development integrated with LOC systems, such as microscale-electrophoresis, microfiltration, micropillars, and magnetic microbeads to perform purification to increase detection sensitivity [ 52 ]. Examples of the biofluids for such applications include whole blood and its derivatives plasma and serum.…”

Section: Sample Purification Via Locmentioning

confidence: 99%

Pushing the detection limits: strategies towards highly sensitive optical-based protein detection

Momenbeitollahi

Cloet

2021

Anal Bioanal Chem

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Proteins are one of the main constituents of living cells. Studying the quantities of proteins under physiological and pathological conditions can give valuable insights into health status, since proteins are the functional molecules of life. To be able to detect and quantify low-abundance proteins in biofluids for applications such as early disease diagnostics, sensitive analytical techniques are desired. An example of this application is using proteins as biomarkers for detecting cancer or neurological diseases, which can provide early, lifesaving diagnoses. However, conventional methods for protein detection such as ELISA, mass spectrometry, and western blotting cannot offer enough sensitivity for certain applications. Recent advances in optical-based micro- and nano-biosensors have demonstrated promising results to detect proteins at low quantities down to the single-molecule level, shining lights on their capacities for ultrasensitive disease diagnosis and rare protein detection. However, to date, there is a lack of review articles synthesizing and comparing various optical micro- and nano-sensing methods of enhancing the limits of detections of the antibody-based protein assays. The purpose of this article is to critically review different strategies of improving assay sensitivity using miniaturized biosensors, such as assay miniaturization, improving antibody binding capacity, sample purification, and signal amplification. The pros and cons of different methods are compared, and the future perspectives of this research field are discussed.

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“…Quantitative detection of these biomarkers has immensely helped in early diagnosis and treatment of these diseases. In order to accurately diagnose these diseases, sensitive assays and biosensing technologies are required to reliably detect minute quantities of these biomarkers [52][53][54] . Therefore, to test the functionalities of our microarray microfluidic devices, aptamer and antibody-based immunoassays were performed to qualitatively and quantitatively detect IL6 and hCRP.…”

Section: Aptamer-based and Antibody-based Immunoassaysmentioning

confidence: 99%

Microcontact printing with aminosilanes: creating biomolecule micro- and nanoarrays for multiplexed microfluidic bioassays

Sathish

Ricoult

Toda‐Peters

et al. 2017

Analyst

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Microfluidic systems integrated with protein and DNA micro- and nanoarrays have been the most sought-after technologies to satisfy the growing demand for high-throughput disease diagnostics. As the sensitivity of these systems relies on the bio-functionalities of the patterned recognition biomolecules, the primary concern has been to develop simple technologies that enable biomolecule immobilization within microfluidic devices whilst preserving bio-functionalities. To address this concern, we introduce a two-step patterning approach to create micro- and nanoarrays of biomolecules within microfluidic devices. First, we introduce a simple aqueous based microcontact printing (μCP) method to pattern arrays of (3-aminopropyl)triethoxysilane (APTES) on glass substrates, with feature sizes ranging from a few hundred microns down to 200 nm (for the first time). Next, these substrates are integrated with microfluidic channels to then covalently couple DNA aptamers and antibodies with the micro- and nanopatterned APTES. As these biomolecules are covalently tethered to the device substrates, the resulting bonds enable them to withstand the high shear stresses originating from the flow in these devices. We further demonstrated the flexibility of this technique, by immobilizing multiple proteins onto these APTES-patterned substrates using liquid-dispensing robots to create multiple microarrays. Next, to validate the functionalities of these microfluidic biomolecule microarrays, we perform (i) aptamer-based sandwich immunoassays to detect human interleukin 6 (IL6); and (ii) antibody-based sandwich immunoassays to detect human c-reactive protein (hCRP) with the limit of detection at 5 nM, a level below the range required for clinical screening. Lastly, the shelf-life potential of these ready-to-use microfluidic microarray devices is validated by effectively functionalizing the patterns with biomolecules up to 3 months post-printing. In summary, with a single printing step, this aminosilane patterning technique enables the creation of functional microfluidic micro- and nano-biomolecule arrays, laying the foundation for high-throughput multiplexed bioassays.

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Whole blood analysis using microfluidic plasma separation and enzyme-linked immunosorbent assay devices

Abstract: In this study, a microfluidic plasma-separation device that realizes the whole blood analysis of C-reactive protein (CRP) using one drop of blood is developed.

Cited by 11 publications

References 36 publications

Automated Microfluidic System with Active Mixing Enables Rapid Analysis of Biomarkers in 5 μL of Whole Blood

Automated Microfluidic System with Active Mixing Enables Rapid Analysis of Biomarkers in 5 μL of Whole Blood

Pushing the detection limits: strategies towards highly sensitive optical-based protein detection

Microcontact printing with aminosilanes: creating biomolecule micro- and nanoarrays for multiplexed microfluidic bioassays

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