Label-free biomarker detection from whole blood

Abstract

Label-free nanosensors can detect disease markers to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive.1-13 However, detecting these biomarkers in physiological fluid samples is difficult because of problems like biofouling and nonspecific binding, and the resulting need to use purified buffers greatly reduces the clinical relevance of these sensors. Here, we overcome this limitation by using distinct components within the sensor to perform purification and detection. A microfluidic purification chip captures multiple biomarkers simultaneously from blood samples and releases them, after washing, into purified buffer for sensing by a silicon nanoribbon detector. This two-stage approach isolates the detector from the complex environment of whole blood, and reduces its minimum required sensitivity by effectively pre-concentrating the biomarkers. We show specific and quantitative detection of two model cancer antigens from a 10 uL sample of whole blood in less than 20 minutes. This study marks the first use of label-free nanosensors with physiologic solutions, positioning this technology for rapid translation to clinical settings.

Frequency-Selective Rotation of Two-Particle Nanoactuators for Rapid and Sensitive Detection of Biomolecules

“…The need for pervasive healthcare drives the field of in vitro diagnostics toward point-of-care solutions to detect biomolecules. − The technological requirements are very demanding, since point-of-care testing needs to be as reliable and quantitative as testing in a centralized laboratory and at the same time a faster response is required (in the order of a few minutes) in a cost-effective, portable, and integrated detection platform that operates on a small sample volume …”

Frequency-Selective Rotation of Two-Particle Nanoactuators for Rapid and Sensitive Detection of Biomolecules

“…The need for pervasive healthcare drives the field of in vitro diagnostics toward point-of-care solutions to detect biomolecules. − The technological requirements are very demanding, since point-of-care testing needs to be as reliable and quantitative as testing in a centralized laboratory and at the same time a faster response is required (in the order of a few minutes) in a cost-effective, portable, and integrated detection platform that operates on a small sample volume …”

A Digital–Analog Microfluidic Platform for Patient-Centric Multiplexed Biomarker Diagnostics of Ultralow Volume Samples

“…Previously, microfluidic approaches generally relied on off-chip hematocyte removal or integrated on-chip separation approaches, , which complicated chip design and assay implementation. Here we show that cell separation − is not necessary, in turn simplifying the assay and enabling multiplexed biomarker detection from an ultralow volume whole blood sample.…”

3D Porous Sol–Gel Matrix Incorporated Microdevice for Effective Large Volume Cell Sample Pretreatment

“…Sol–gel is a chemically inert and porous stable substance, with which it is easy to modify a surface. Several groups have synthesized the sol–gel to tightly “pack” a microchannel and act as “glue”, and used the resultant sol–gel monolith to extract nucleic acids from biological samples on a microchip. − A sol–gel material was also reported to be safe for biomolecule immobilization . In this study, we demonstrated that a sol–gel matrix could be used for immunoaffinity reactions and as a pathogen sample pretreatment device.…”

Frequency-Selective Rotation of Two-Particle Nanoactuators for Rapid and Sensitive Detection of Biomolecules

“…The need for pervasive healthcare drives the field of in vitro diagnostics toward point-of-care solutions to detect biomolecules. − The technological requirements are very demanding, since point-of-care testing needs to be as reliable and quantitative as testing in a centralized laboratory and at the same time a faster response is required (in the order of a few minutes) in a cost-effective, portable, and integrated detection platform that operates on a small sample volume …”

A Digital–Analog Microfluidic Platform for Patient-Centric Multiplexed Biomarker Diagnostics of Ultralow Volume Samples

“…Previously, microfluidic approaches generally relied on off-chip hematocyte removal or integrated on-chip separation approaches, , which complicated chip design and assay implementation. Here we show that cell separation − is not necessary, in turn simplifying the assay and enabling multiplexed biomarker detection from an ultralow volume whole blood sample.…”

3D Porous Sol–Gel Matrix Incorporated Microdevice for Effective Large Volume Cell Sample Pretreatment

“…Sol–gel is a chemically inert and porous stable substance, with which it is easy to modify a surface. Several groups have synthesized the sol–gel to tightly “pack” a microchannel and act as “glue”, and used the resultant sol–gel monolith to extract nucleic acids from biological samples on a microchip. − A sol–gel material was also reported to be safe for biomolecule immobilization . In this study, we demonstrated that a sol–gel matrix could be used for immunoaffinity reactions and as a pathogen sample pretreatment device.…”

Frequency-Selective Rotation of Two-Particle Nanoactuators for Rapid and Sensitive Detection of Biomolecules

“…The need for pervasive healthcare drives the field of in vitro diagnostics toward point-of-care solutions to detect biomolecules. − The technological requirements are very demanding, since point-of-care testing needs to be as reliable and quantitative as testing in a centralized laboratory and at the same time a faster response is required (in the order of a few minutes) in a cost-effective, portable, and integrated detection platform that operates on a small sample volume …”

A Digital–Analog Microfluidic Platform for Patient-Centric Multiplexed Biomarker Diagnostics of Ultralow Volume Samples

“…Previously, microfluidic approaches generally relied on off-chip hematocyte removal or integrated on-chip separation approaches, , which complicated chip design and assay implementation. Here we show that cell separation − is not necessary, in turn simplifying the assay and enabling multiplexed biomarker detection from an ultralow volume whole blood sample.…”

3D Porous Sol–Gel Matrix Incorporated Microdevice for Effective Large Volume Cell Sample Pretreatment

“…Sol–gel is a chemically inert and porous stable substance, with which it is easy to modify a surface. Several groups have synthesized the sol–gel to tightly “pack” a microchannel and act as “glue”, and used the resultant sol–gel monolith to extract nucleic acids from biological samples on a microchip. − A sol–gel material was also reported to be safe for biomolecule immobilization . In this study, we demonstrated that a sol–gel matrix could be used for immunoaffinity reactions and as a pathogen sample pretreatment device.…”