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Article ; Online: Improving the Quantification of Colorimetric Signals in Paper-Based Immunosensors with an Open-Source Reader.

Russell, Steven M / Alba-Patiño, Alejandra / Vaquer, Andreu / Clemente, Antonio / de la Rica, Roberto

2022 Volume 22, Issue 5

Abstract: Measuring the colorimetric signals produced by the biospecific accumulation of colorimetric probes and recording the results is a key feature for next-generation paper-based rapid tests. Manual processing of these tests is time-consuming and prone to a ... ...

Abstract	Measuring the colorimetric signals produced by the biospecific accumulation of colorimetric probes and recording the results is a key feature for next-generation paper-based rapid tests. Manual processing of these tests is time-consuming and prone to a loss of accuracy when interpreting faint and patchy signals. Proprietary, closed-source readers and software companies offering automated smartphone-based assay readings have both been criticized for interoperability issues. Here, we introduce a minimal reader prototype composed of open-source hardware and open-source software that has the benefits of automatic assay quantification while avoiding the interoperability issues associated with closed-source readers. An image-processing algorithm was developed to automate the selection of an optimal region of interest and measure the average pixel intensity. When used to quantify signals produced by lateral flow immunoassays for detecting antibodies against SARS-CoV-2, results obtained with the proposed algorithm were comparable to those obtained with a manual method but with the advantage of improving the precision and accuracy when quantifying small spots or faint and patchy signals.
MeSH term(s)	Biosensing Techniques ; COVID-19/diagnosis ; Colorimetry/methods ; Humans ; Immunoassay/methods ; SARS-CoV-2
Language	English
Publishing date	2022-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2052857-7
ISSN	1424-8220 ; 1424-8220
ISSN (online)	1424-8220
ISSN	1424-8220
DOI	10.3390/s22051880
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Nanoparticle Reservoirs for Paper-Only Immunosensors.

Alba-Patiño, Alejandra / Adrover-Jaume, Cristina / Rica, Roberto de la

ACS sensors

2020 Volume 5, Issue 1, Page(s) 147–153

Abstract: Biosensors made entirely of paper are becoming increasingly popular due to their low cost, facile fabrication, and lightweight portability for in-field measurements. However, it is difficult to store nanoparticles in paper substrates without irreversibly ...

Abstract	Biosensors made entirely of paper are becoming increasingly popular due to their low cost, facile fabrication, and lightweight portability for in-field measurements. However, it is difficult to store nanoparticles in paper substrates without irreversibly binding them to the cellulose matrix. This makes it challenging to fabricate biosensors incorporating nanoparticle probes in paper-based reservoirs. Here, we overcome this limitation with a new method for storing protein-decorated nanoparticles on paper substrates that also allows to release them on demand. It consists of spotting nanoparticles onto pieces of filter paper previously modified with polystyrene sulfonate. Gold nanoparticles modified with avidin or antibodies can be easily transferred from the dry reservoir to a receiving wet piece of paper by simply pressing with the finger or a clamp. Paper-based immunosensors incorporating the reservoir enabled the detection of glycoprotein B from human cytomegalovirus in serum with a limit of detection of 0.03 ng mL
MeSH term(s)	Biosensing Techniques/methods ; Humans ; Metal Nanoparticles/chemistry
Language	English
Publishing date	2020-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3694
ISSN (online)	2379-3694
DOI	10.1021/acssensors.9b01937
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Article ; Online: Micro- and nanosensors for detecting blood pathogens and biomarkers at different points of sepsis care.

Alba-Patiño, Alejandra / Vaquer, Andreu / Barón, Enrique / Russell, Steven M / Borges, Marcio / de la Rica, Roberto

Mikrochimica acta

2022 Volume 189, Issue 2, Page(s) 74

Abstract: Severe infections can cause a dysregulated response leading to organ dysfunction known as sepsis. Sepsis can be lethal if not identified and treated right away. This requires measuring biomarkers and pathogens rapidly at the different points where sepsis ...

Abstract	Severe infections can cause a dysregulated response leading to organ dysfunction known as sepsis. Sepsis can be lethal if not identified and treated right away. This requires measuring biomarkers and pathogens rapidly at the different points where sepsis care is provided. Current commercial approaches for sepsis diagnosis are not fast, sensitive, and/or specific enough for meeting this medical challenge. In this article, we review recent advances in the development of diagnostic tools for sepsis management based on micro- and nanostructured materials. We start with a brief introduction to the most popular biomarkers for sepsis diagnosis (lactate, procalcitonin, cytokines, C-reactive protein, and other emerging protein and non-protein biomarkers including miRNAs and cell-based assays) and methods for detecting bacteremia. We then highlight the role of nano- and microstructured materials in developing biosensors for detecting them taking into consideration the particular needs of every point of sepsis care (e.g., ultrafast detection of multiple protein biomarkers for diagnosing in triage, emergency room, ward, and intensive care unit; quantitative detection to de-escalate treatment; ultrasensitive and culture-independent detection of blood pathogens for personalized antimicrobial therapies; robust, portable, and web-connected biomarker tests outside the hospital). We conclude with an overview of the most utilized nano- and microstructured materials used thus far for solving issues related to sepsis diagnosis and point to new challenges for future development.
MeSH term(s)	Bacteria/isolation & purification ; Biomarkers/blood ; Biosensing Techniques/instrumentation ; Cytokines/blood ; Cytokines/chemistry ; Humans ; Nanotechnology ; Sepsis/blood ; Sepsis/diagnosis ; Sepsis/microbiology
Chemical Substances	Biomarkers ; Cytokines
Language	English
Publishing date	2022-01-26
Publishing country	Austria
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	89-9
ISSN	1436-5073 ; 0026-3672
ISSN (online)	1436-5073
ISSN	0026-3672
DOI	10.1007/s00604-022-05171-2
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Article: Multifunctional motion-to-color janus transducers for the rapid detection of sepsis biomarkers in whole blood

Russell, Steven M / Alba-Patiño, Alejandra / Borges, Marcio / de la Rica, Roberto

Biosensors & bioelectronics. 2019 Sept. 01, v. 140

2019

Abstract: Self-propelled particles are revolutionizing sensing applications thanks to a unique motion-based signal generation mechanism in which biorecognition reactions are detected as changes in the velocity of the colloids. Here a new family of self-propelled ... ...

Abstract	Self-propelled particles are revolutionizing sensing applications thanks to a unique motion-based signal generation mechanism in which biorecognition reactions are detected as changes in the velocity of the colloids. Here a new family of self-propelled multifunctional Janus particles is introduced that enables detecting changes in particle motion colorimetrically. The particles consist of an iron oxide core that provides color and magnetism, and a Janus coating that provides biospecific recognition and locomotive properties. In this approach, biomolecular interactions trigger changes in particle motion that are detected as variations in color when spotted on a piece of paper. These variations in color are then read and quantified with a custom-made smartphone app. The high surface area and magnetism of the particles makes them ideal building blocks for developing biosensors because they allow for the rapid capture of a target molecule and the removal of non-specific interactions. Biosensors engineered with the proposed multifunctional particles were able to detect the sepsis biomarker procalcitonin at clinically relevant concentrations within 13 min in whole blood, which is faster than other approaches requiring hour-long incubation steps under controlled conditions to detect the same biomarker in purified serum. The short assay time along with the point-of-need design makes these biosensors suitable for stratifying patients according to their sepsis risk level during triage independently of resource constraints.
Keywords	biomarkers ; biosensors ; blood serum ; coatings ; colloids ; color ; iron oxides ; magnetism ; mobile telephones ; paper ; patients ; rapid methods ; risk ; sepsis (infection) ; surface area
Language	English
Dates of publication	2019-0901
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1011023-9
ISSN	1873-4235 ; 0956-5663
ISSN (online)	1873-4235
ISSN	0956-5663
DOI	10.1016/j.bios.2019.111346
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Multifunctional motion-to-color janus transducers for the rapid detection of sepsis biomarkers in whole blood.

Russell, Steven M / Alba-Patiño, Alejandra / Borges, Marcio / de la Rica, Roberto

Biosensors & bioelectronics

2019 Volume 140, Page(s) 111346

Abstract	Self-propelled particles are revolutionizing sensing applications thanks to a unique motion-based signal generation mechanism in which biorecognition reactions are detected as changes in the velocity of the colloids. Here a new family of self-propelled multifunctional Janus particles is introduced that enables detecting changes in particle motion colorimetrically. The particles consist of an iron oxide core that provides color and magnetism, and a Janus coating that provides biospecific recognition and locomotive properties. In this approach, biomolecular interactions trigger changes in particle motion that are detected as variations in color when spotted on a piece of paper. These variations in color are then read and quantified with a custom-made smartphone app. The high surface area and magnetism of the particles makes them ideal building blocks for developing biosensors because they allow for the rapid capture of a target molecule and the removal of non-specific interactions. Biosensors engineered with the proposed multifunctional particles were able to detect the sepsis biomarker procalcitonin at clinically relevant concentrations within 13 min in whole blood, which is faster than other approaches requiring hour-long incubation steps under controlled conditions to detect the same biomarker in purified serum. The short assay time along with the point-of-need design makes these biosensors suitable for stratifying patients according to their sepsis risk level during triage independently of resource constraints.
MeSH term(s)	Animals ; Biomarkers/blood ; Biosensing Techniques/instrumentation ; Catalase/chemistry ; Colorimetry/instrumentation ; Enzymes, Immobilized/chemistry ; Humans ; Immunoenzyme Techniques/instrumentation ; Magnets/chemistry ; Mice ; Mobile Applications ; Motion ; Procalcitonin/blood ; Sepsis/blood ; Smartphone ; Transducers
Chemical Substances	Biomarkers ; Enzymes, Immobilized ; Procalcitonin ; Catalase (EC 1.11.1.6)
Language	English
Publishing date	2019-05-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1011023-9
ISSN	1873-4235 ; 0956-5663
ISSN (online)	1873-4235
ISSN	0956-5663
DOI	10.1016/j.bios.2019.111346
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Article ; Online: Biosensors for Managing the COVID-19 Cytokine Storm: Challenges Ahead.

Russell, Steven M / Alba-Patiño, Alejandra / Barón, Enrique / Borges, Marcio / Gonzalez-Freire, Marta / de la Rica, Roberto

ACS sensors

2020 Volume 5, Issue 6, Page(s) 1506–1513

Abstract: The global COVID-19 pandemic has oversaturated many intensive care units to the point of collapse, leading to enormous spikes in death counts. Before critical care becomes a necessity, identifying patients who are likely to become critically ill and ... ...

Abstract	The global COVID-19 pandemic has oversaturated many intensive care units to the point of collapse, leading to enormous spikes in death counts. Before critical care becomes a necessity, identifying patients who are likely to become critically ill and providing prompt treatment is a strategy to avoid ICU oversaturation. There is a consensus that a hyperinflammatory syndrome or a "cytokine storm" is responsible for poor outcomes in COVID-19. Measuring cytokine levels at the point of care is required in order to better understand this process. In this Perspective, we summarize the main events behind the cytokine storm in COVID-19 as well as current experimental treatments. We advocate for a new biosensor-enabled paradigm to personalize the management of COVID-19 and stratify patients. Biosensor-guided dosing and timing of immunomodulatory therapies could maximize the benefits of these anti-inflammatory treatments while minimizing deleterious effects. Biosensors will also be essential in order to detect complications such as coinfections and sepsis, which are common in immunosuppressed patients. Finally, we propose the ideal features of these biosensors using some prototypes from the recent literature as examples. Multisensors, lateral flow tests, mobile biosensors, and wearable biosensors are seen as key players for precision medicine in COVID-19.
MeSH term(s)	Betacoronavirus ; Biosensing Techniques/methods ; COVID-19 ; Coronavirus Infections/diagnosis ; Coronavirus Infections/immunology ; Coronavirus Infections/therapy ; Cytokines/analysis ; Cytokines/immunology ; Humans ; Immunomodulation ; Inflammation ; Interleukin-6/analysis ; Interleukin-6/immunology ; Pandemics ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/immunology ; Pneumonia, Viral/therapy ; Precision Medicine ; SARS-CoV-2 ; Sepsis
Chemical Substances	Cytokines ; IL6 protein, human ; Interleukin-6
Keywords	covid19
Language	English
Publishing date	2020-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2379-3694
ISSN (online)	2379-3694
DOI	10.1021/acssensors.0c00979
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Nanoparticle-based mobile biosensors for the rapid detection of sepsis biomarkers in whole blood.

Alba-Patiño, Alejandra / Russell, Steven M / Borges, Marcio / Pazos-Pérez, Nicolás / Álvarez-Puebla, Ramón A / de la Rica, Roberto

Nanoscale advances

2020 Volume 2, Issue 3, Page(s) 1253–1260

Abstract: Detecting small variations in the levels of IL-6 is crucial for the early diagnosis of sepsis. To be useful in clinical decision-making, this requires detecting IL-6 rapidly in whole blood and with portable readers. Here we introduce immunosensors made ... ...

Abstract	Detecting small variations in the levels of IL-6 is crucial for the early diagnosis of sepsis. To be useful in clinical decision-making, this requires detecting IL-6 rapidly in whole blood and with portable readers. Here we introduce immunosensors made of filter paper that use plasmonic nanoprobes to detect IL-6 rapidly in unprocessed blood with an unmodified smartphone. Key aspects of the biosensor fabrication were optimized in order to reduce the assay time without losing sensitivity. This included testing three bioconjugation routes for protein attachment to nanoprobes using gold nanoparticles covered with carboxylate or amine moieties, or polyvinylpyrrolidone (PVP), as starting materials, and using alternating layers of polyelectrolytes to bind the capture antibody to the paper substrate. Smartphone-based signal quantification was achieved with a custom-made app featuring a unique augmented reality guidance system that circumvents the need for smartphone attachments and automates all the steps involved in color quantification. The biosensors were able to detect IL-6 with a limit of detection of 0.1 pg mL
Language	English
Publishing date	2020-01-22
Publishing country	England
Document type	Journal Article
ISSN	2516-0230
ISSN (online)	2516-0230
DOI	10.1039/d0na00026d
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Rapid Detection of

Clemente, Antonio / Alba-Patiño, Alejandra / Rojo-Molinero, Estrella / Russell, Steven M / Borges, Marcio / Oliver, Antonio / de la Rica, Roberto

ACS sensors

2020 Volume 5, Issue 12, Page(s) 3956–3963

Abstract: Respiratory infections caused by multi-drug- ... ...

Abstract	Respiratory infections caused by multi-drug-resistant
MeSH term(s)	Bacteria ; Biofilms ; Humans ; Pseudomonas aeruginosa ; Sensitivity and Specificity ; Sputum
Language	English
Publishing date	2020-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-3694
ISSN (online)	2379-3694
DOI	10.1021/acssensors.0c01618
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Article ; Online: A Robust and User-Friendly Alternative to Densitometry Using Origami Biosensors and Digital Logic.

Russell, Steven M / Alba-Patiño, Alejandra / Borges, Marcio / de la Rica, Roberto

ACS sensors

2018 Volume 3, Issue 9, Page(s) 1712–1718

Abstract: Colorimetric detection with smartphones is ideal for point-of-care measurements because the signal reader is easily available. Densitometric detection schemes enable semiquantitative measurements but require a lightproof box to control photographic ... ...

Abstract	Colorimetric detection with smartphones is ideal for point-of-care measurements because the signal reader is easily available. Densitometric detection schemes enable semiquantitative measurements but require a lightproof box to control photographic conditions and/or extensive data treatment to extract information. Approaches based on pattern recognition are not so sensitive to light artifacts but can only yield a yes/no type of answer when the signal is above or below a certain threshold. Here, we introduce a new method for detecting different concentrations of proteins as well as light artifacts with origami immunosensors and digital logic. The origami design consists of a folded piece of paper with three identical biorecognition sites so that one drop of sample generates three colorimetric signals simultaneously. The three colorimetric signals are then evaluated with an augmented reality app that generates a virtual semaphore that sequentially turns on its green, yellow, and red lights depending on the concentration of analyte. These three Boolean variables pass through "and" and "not" logic gates in a 3-to-8 decoder that enables the semiquantitative detection of proteins and adds a failsafe against erroneous results. The proposed method can detect the model analyte mouse IgG with a limit of detection and sensitivity comparable to densitometry performed under light-controlled conditions. It can also detect the sepsis biomarker procalcitonin at clinically relevant concentrations. With our approach, the detection is performed in real time, and signal processing is not required, which makes it suitable for rapid analyses by nonspecialists at the point of need.
MeSH term(s)	Animals ; Antibodies/immunology ; Biosensing Techniques/methods ; Color ; Colorimetry/methods ; Gold/chemistry ; Humans ; Immunoassay/instrumentation ; Immunoassay/methods ; Immunoglobulin G/analysis ; Immunoglobulin G/immunology ; Limit of Detection ; Logic ; Metal Nanoparticles/chemistry ; Mice ; Nucleic Acid Conformation ; Paper ; Procalcitonin/analysis ; Procalcitonin/immunology ; Smartphone ; Software
Chemical Substances	Antibodies ; Immunoglobulin G ; Procalcitonin ; Gold (7440-57-5)
Language	English
Publishing date	2018-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ISSN	2379-3694
ISSN (online)	2379-3694
DOI	10.1021/acssensors.8b00452
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Immunodetection of Lung IgG and IgM Antibodies against SARS-CoV-2 via Enzymatic Liquefaction of Respiratory Samples from COVID-19 Patients.

Clemente, Antonio / Alba-Patiño, Alejandra / Santopolo, Giulia / Rojo-Molinero, Estrella / Oliver, Antonio / Borges, Marcio / Aranda, María / Del Castillo, Alberto / de la Rica, Roberto

Analytical chemistry

2021 Volume 93, Issue 12, Page(s) 5259–5266

Abstract: Lung-secreted IgG and IgM antibodies are valuable biomarkers for monitoring the local immune response against respiratory infections. These biomarkers are found in lower airway secretions that need to be liquefied prior to analysis. Traditional methods ... ...

Abstract	Lung-secreted IgG and IgM antibodies are valuable biomarkers for monitoring the local immune response against respiratory infections. These biomarkers are found in lower airway secretions that need to be liquefied prior to analysis. Traditional methods for sample liquefaction rely on reducing disulfide bonds, which may damage the structure of the biomarkers and hamper their immunodetection. Here, we propose an alternative enzymatic method that uses O
MeSH term(s)	Antibodies, Viral/immunology ; COVID-19/immunology ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunoglobulin G/immunology ; Immunoglobulin M/immunology ; Limit of Detection ; Lung/immunology ; SARS-CoV-2/immunology
Chemical Substances	Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M
Language	English
Publishing date	2021-03-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.1c00251
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