Early sepsis diagnosis via protein and miRNA biomarkers using a novel point-of-care photonic biosensor

Fabri-Faja, Nuria; Calvo-Lozano, Olalla; Dey, Priyanka; Terborg, Roland A.; Estévez, M.‐Carmen; Belushkin, Alexander; Yesilköy, Filiz; Duempelmann, Luc; Altug, Hatice; Pruneri, Valerio; Lechuga, Laura M.

doi:10.1016/j.aca.2019.05.038

Cited by 82 publications

(56 citation statements)

References 27 publications

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“…Coupling of this technique with enzyme-linked immunosorbent assay (ELISA) has been achieved [128], demonstrating the feasibility of this approach. Optics comprised of interferometric biosensors coupled with immunoassay have been constructed, using antibodies to CRP and IL-6 which are linked directly to the sensor chip, thereby removing the requirement of a second, labelled antibody [129]. Although the concept in this study was to provide multiplex measurement of CRP and IL-6, the results suggested that there was some degree of cross reactivity and the authors concede that the use of a second antibody and reverting to the more traditional sandwich antibody format may be necessary.…”

Section: Point-of-care Testing (Poct) For Sepsismentioning

confidence: 99%

Biomarkers for Point-of-Care Diagnosis of Sepsis

2020

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Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In 2017, almost 50 million cases of sepsis were recorded worldwide and 11 million sepsis-related deaths were reported. Therefore, sepsis is the focus of intense research to better understand the complexities of sepsis response, particularly the twin underlying concepts of an initial hyper-immune response and a counter-immunological state of immunosuppression triggered by an invading pathogen. Diagnosis of sepsis remains a significant challenge. Prompt diagnosis is essential so that treatment can be instigated as early as possible to ensure the best outcome, as delay in treatment is associated with higher mortality. In order to address this diagnostic problem, use of a panel of biomarkers has been proposed as, due to the complexity of the sepsis response, no single marker is sufficient. This review provides background on the current understanding of sepsis in terms of its epidemiology, the evolution of the definition of sepsis, pathobiology and diagnosis and management. Candidate biomarkers of interest and how current and developing point-of-care testing approaches could be used to measure such biomarkers is discussed.

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Section: Point-of-care Testing (Poct) For Sepsismentioning

confidence: 99%

Biomarkers for Point-of-Care Diagnosis of Sepsis

2020

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“…Among precursors of modern biosensor technologies are such diagnostic platforms as quantitative and semi-quantitative test systems for identifying specific antigens [9] and antibodies [10] as well as gene amplification products [11][12][13][14] based on latex agglutination and lateral flow immunoassay (LFIA). In the past decades, these tools have been successfully used to diagnose and identify molecular markers of infection, and they have not lost their biomedical significance today [10,11,13,15] (Figure 1).…”

Section: Lateral Flow Immunoassay (Lfia) As Simplified Formats Of Modmentioning

confidence: 99%

“…It is interesting that the evolution of sensory technologies developed in parallel with the emergence of diagnostic platforms for the lateral flow immunoassay (LFIA), which in our time are considered as simplified formats of modern biosensors [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…The emergence and use of biosensors based on integrative constructive strategies has enabled these devices in recent decades to be widely used in various fields of science, medicine, pharmacology, biological and food safety, and environmental protection. This biotechnological breakthrough was the result of the development and creation of powerful and sensitive analytical tools that use biological molecular elements as sensors [11,13,18].…”

Section: Introduction To Biosensor Technologiesmentioning

confidence: 99%

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Label-Free Biosensors for Laboratory-Based Diagnostics of Infections: Current Achievements and New Trends

et al. 2020

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Infections pose a serious global public health problem and are a major cause of premature mortality worldwide. One of the most challenging objectives faced by modern medicine is timely and accurate laboratory-based diagnostics of infectious diseases. Being a key factor of timely initiation and success of treatment, it may potentially provide reduction in incidence of a disease, as well as prevent outbreak and spread of dangerous epidemics. The traditional methods of laboratory-based diagnostics of infectious diseases are quite time- and labor-consuming, require expensive equipment and qualified personnel, which restricts their use in case of limited resources. Over the past six decades, diagnostic technologies based on lateral flow immunoassay (LFIA) have been and remain true alternatives to modern laboratory analyzers and have been successfully used to quickly detect molecular ligands in biosubstrates to diagnose many infectious diseases and septic conditions. These devices are considered as simplified formats of modern biosensors. Recent advances in the development of label-free biosensor technologies have made them promising diagnostic tools that combine rapid pathogen indication, simplicity, user-friendliness, operational efficiency, accuracy, and cost effectiveness, with a trend towards creation of portable platforms. These qualities exceed the generally accepted standards of microbiological and immunological diagnostics and open up a broad range of applications of these analytical systems in clinical practice immediately at the site of medical care (point-of-care concept, POC). A great variety of modern nanoarchitectonics of biosensors are based on the use of a broad range of analytical and constructive strategies and identification of various regulatory and functional molecular markers associated with infectious bacterial pathogens. Resolution of the existing biosensing issues will provide rapid development of diagnostic biotechnologies.

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“…For example, interferometric SPR can achieve LODs of Δn ≈ 10 −8 , but this sensitivity is only achieved over 5 × 10 −5 RIU, unless advanced designs are used that are costly, cumbersome, and not suitable for POC applications 7 . An alternative and intrinsically simpler approach is to exploit the phase sensitivity of goldnanohole arrays 9 , which have shown LODs on the order of 10 −4 RIU with a detection limit for proteins in tens of µg mL −1 range 10 . The goal of our work, which is targeted at POC applications, is to maintain simplicity while improving both the sensitivity and the dynamic range.…”

Section: Introductionmentioning

confidence: 99%

Common-path interferometric label-free protein sensing with resonant dielectric nanostructures

et al. 2020

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Research toward photonic biosensors for point-of-care applications and personalized medicine is driven by the need for high-sensitivity, low-cost, and reliable technology. Among the most sensitive modalities, interferometry offers particularly high performance, but typically lacks the required operational simplicity and robustness. Here, we introduce a common-path interferometric sensor based on guided-mode resonances to combine high performance with inherent stability. The sensor exploits the simultaneous excitation of two orthogonally polarized modes, and detects the relative phase change caused by biomolecular binding on the sensor surface. The wide dynamic range of the sensor, which is essential for fabrication and angle tolerance, as well as versatility, is controlled by integrating multiple, tuned structures in the field of view. This approach circumvents the trade-off between sensitivity and dynamic range, typical of other phase-sensitive modalities, without increasing complexity. Our sensor enables the challenging label-free detection of procalcitonin, a small protein (13 kDa) and biomarker for infection, at the clinically relevant concentration of 1 pg mL −1 , with a signal-to-noise ratio of 35. This result indicates the utility for an exemplary application in antibiotic guidance, and opens possibilities for detecting further clinically or environmentally relevant small molecules with an intrinsically simple and robust sensing modality.

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Early sepsis diagnosis via protein and miRNA biomarkers using a novel point-of-care photonic biosensor

Cited by 82 publications

References 27 publications

Biomarkers for Point-of-Care Diagnosis of Sepsis

Biomarkers for Point-of-Care Diagnosis of Sepsis

Label-Free Biosensors for Laboratory-Based Diagnostics of Infections: Current Achievements and New Trends

Common-path interferometric label-free protein sensing with resonant dielectric nanostructures

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