scholarly journals A Portable Microfluidic System for Point-of-Care Detection of Multiple Protein Biomarkers

Micromachines ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 347
Author(s):  
Nan Li ◽  
Minjie Shen ◽  
Youchun Xu

Protein biomarkers are indicators of many diseases and are commonly used for disease diagnosis and prognosis prediction in the clinic. The urgent need for point-of-care (POC) detection of protein biomarkers has promoted the development of automated and fully sealed immunoassay platforms. In this study, a portable microfluidic system was established for the POC detection of multiple protein biomarkers by combining a protein microarray for a multiplex immunoassay and a microfluidic cassette for reagent storage and liquid manipulation. The entire procedure for the immunoassay was automatically conducted, which included the antibody–antigen reaction, washing and detection. Alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carcinoma antigen 125 (CA125) were simultaneously detected in this system within 40 min with limits of detection of 0.303 ng/mL, 1.870 ng/mL, and 18.617 U/mL, respectively. Five clinical samples were collected and tested, and the results show good correlations compared to those measured by the commercial instrument in the hospital. The immunoassay cassette system can function as a versatile platform for the rapid and sensitive multiplexed detection of biomarkers; therefore, it has great potential for POC diagnostics.

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Ziad J. Sahab ◽  
Suzan M. Semaan ◽  
Qing-Xiang Amy Sang

Biomarkers are biomolecules that serve as indicators of biological and pathological processes, or physiological and pharmacological responses to a drug treatment. Because of the high abundance of albumin and heterogeneity of plasma lipoproteins and glycoproteins, biomarkers are difficult to identify in human serum. Due to the clinical significance the identification of disease biomarkers in serum holds great promise for personalized medicine, especially for disease diagnosis and prognosis. This review summarizes some common and emerging proteomics techniques utilized in the separation of serum samples and identification of disease signatures. The practical application of each protein separation or identification technique is analyzed using specific examples. Biomarkers of cancers of prostate, breast, ovary, and lung in human serum have been reviewed, as well as those of heart disease, arthritis, asthma, and cystic fibrosis. Despite the advancement of technology few biomarkers have been approved by the Food and Drug Administration for disease diagnosis and prognosis due to the complexity of structure and function of protein biomarkers and lack of high sensitivity, specificity, and reproducibility for those putative biomarkers. The combination of different types of technologies and statistical analysis may provide more effective methods to identify and validate new disease biomarkers in blood.


2015 ◽  
Vol 112 (32) ◽  
pp. E4354-E4363 ◽  
Author(s):  
Fatih Inci ◽  
Chiara Filippini ◽  
Murat Baday ◽  
Mehmet Ozgun Ozen ◽  
Semih Calamak ◽  
...  

Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients’ homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE2RD), which addresses all these impediments on a single platform. The NE2RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE2RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE2RD’s broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients’ homes.


2019 ◽  
Vol 21 (1) ◽  
pp. 134 ◽  
Author(s):  
Wei Xu ◽  
Daniel Wang ◽  
Derek Li ◽  
Chung Chiun Liu

Detection of biomarkers has raised much interest recently due to the need for disease diagnosis and personalized medicine in future point-of-care systems. Among various biomarkers, antibodies are an important type of detection target due to their potential for indicating disease progression stage and the efficiency of therapeutic antibody drug treatment. In this review, electrochemical and optical detection of antibodies are discussed. Specifically, creating a non-label and reagent-free sensing platform and construction of an anti-fouling electrochemical surface for electrochemical detection are suggested. For optical transduction, a rapid and programmable platform for antibody detection using a DNA-based beacon is suggested as well as the use of bioluminescence resonance energy transfer (BRET) switch for low cost antibody detection. These sensing strategies have demonstrated their potential for resolving current challenges in antibody detection such as high selectivity, low operation cost, simple detection procedures, rapid detection, and low-fouling detection. This review provides a general update for recent developments in antibody detection strategies and potential solutions for future clinical point-of-care systems.


2021 ◽  
Author(s):  
Pei-Heng Lin ◽  
Bor-Ran Li

Abstract Since polymerase chain reaction (PCR) has become a vital tool for disease diagnosis, the development of precise applied PCR technologies in point-of care testing (POCT) has become more significant. The microfluidic-based PCR platform offers a great opportunity for on-site diagnosis efficiency, and the system is aimed at user-friendly access. Herein, we demonstrate a microfluidic system with simple operation that provides reliable nucleic acid results from 18 uniform droplets via LAMP qPCR detection. By using only micropipette regulation, users are able to control the nanoliter scale of the droplets in this valve-free and pump-free microfluidic (MF) chip. Based on the oil enclosure method and impermeable fabrication, we successfully preserved the reagent inside the microfluidic system, which significantly reduced the fluid loss and condensation. The relative standard deviation (RSD) of the fluorescence intensity between the droplets and during the heating process was <5% and 2.0%, respectively. Additionally, for different nucleic acid detection methods, the MF-LAMP chip in this study showed good applicability to both genome detection and gene expression analysis.


Biosensors ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 296
Author(s):  
Özgecan Erdem ◽  
Ismail Eş ◽  
Garbis Atam Akceoglu ◽  
Yeşeren Saylan ◽  
Fatih Inci

Chronic diseases (CDs) are noncommunicable illnesses with long-term symptoms accounting for ~70% of all deaths worldwide. For the diagnosis and prognosis of CDs, accurate biomarker detection is essential. Currently, the detection of CD-associated biomarkers is employed through complex platforms with certain limitations in their applicability and performance. There is hence unmet need to present innovative strategies that are applicable to the point-of-care (PoC) settings, and also, provide the precise detection of biomarkers. On the other hand, especially at PoC settings, microneedle (MN) technology, which comprises micron-size needles arranged on a miniature patch, has risen as a revolutionary approach in biosensing strategies, opening novel horizons to improve the existing PoC devices. Various MN-based platforms have been manufactured for distinctive purposes employing several techniques and materials. The development of MN-based biosensors for real-time monitoring of CD-associated biomarkers has garnered huge attention in recent years. Herein, we summarize basic concepts of MNs, including microfabrication techniques, design parameters, and their mechanism of action as a biosensing platform for CD diagnosis. Moreover, recent advances in the use of MNs for CD diagnosis are introduced and finally relevant clinical trials carried out using MNs as biosensing devices are highlighted. This review aims to address the potential use of MNs in CD diagnosis.


2008 ◽  
Vol 1106 ◽  
Author(s):  
Manish Bothara ◽  
Ravi K Reddy ◽  
Thomas Barrett ◽  
John Carruthers ◽  
Shalini Prasad

AbstractThe objective of this research is to develop a “point-of-care” device for early disease diagnosis through protein biomarker characterization. Here we present label-free, high sensitivity detection of proteins with the use of electrical immunoassays that we call Nanomonitors. The basis of the detection principle lies in the formation of an electrical double layer and its perturbations caused by proteins trapped in a nanoporous alumina membrane over a microelectrode array platform. High sensitivity and rapid detection of two inflammatory biomarkers, C-reactive protein (CRP) and Myeloperoxidase (MPO) in pure and clinical samples through label-free electrical detection were achieved. The performance metrics achieved by this device makes it suitable as a “lab-on-a-chip” device for protein biomarker profiling and hence early disease diagnosis.


2019 ◽  
Vol 19 (6) ◽  
pp. 387-394 ◽  
Author(s):  
Li Xu ◽  
Long-Fei Wu ◽  
Fei-Yan Deng

Exosomes are 30-120nm long endocytic membrane-derived vesicles, which are secreted by various types of cells and stably present in body fluids, such as plasma, urine, saliva and breast milk. Exosomes participate in intercellular communication. Recently accumulative studies have suggested that exosomes may serve as novel biomarkers for disease diagnosis and prognosis. Herein, we reviewed the biological features of exosomes, technologies for exosome isolation and identification, as well as progress in exosomal biomarker identification, highlighting the relevance of exosome to human diseases and significance and great potential in translational medicine.


Author(s):  
Seyed Ali Tabatabaei ◽  
Mohammad Zabetian Targhi

Isolation of microparticles and biological cells on microfluidic chips has received considerable attention due to their applications in numerous areas such as medical and engineering fields. Microparticles separation is of great importance in bioassays due to the need for smaller sample and device size and lower manufacturing costs. In this study, we first explain the concepts of separation and microfluidic science along with their applications in the medical sciences, and then, a conceptual design of a novel inertial microfluidic system is proposed and analyzed. The PDMS spiral microfluidic device was fabricated, and its effects on the separation of particles with sizes similar to biological particles were experimentally analyzed. This separation technique can be used to separate cancer cells from the normal ones in the blood samples. These components required for testing were selected, assembled, and finally, a very affordable microfluidic kit was provided. Different experiments were designed, and the results were analyzed using appropriate software and methods. Separator system tests with polydisperse hollow glass particles (diameter 2–20 µm), and monodisperse Polystyrene particles (diameter 5 & 15 µm), and the results exhibit an acceptable chip performance with 86% of efficiency for both monodisperse particles and polydisperse particles. The microchannel collects particles with an average diameter of 15.8, 9.4, and 5.9 μm at the proposed reservoirs. This chip can be integrated into a more extensive point-of-care diagnostic system to test blood samples.


Diagnosis ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Gian Luca Salvagno ◽  
Gianluca Gianfilippi ◽  
Damiano Bragantini ◽  
Brandon M. Henry ◽  
Giuseppe Lippi

Abstract Objectives Novel point-of-care antigen assays present a promising opportunity for rapid screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The purpose of this study was the clinical assessment of the new Roche SARS-CoV-2 Rapid Antigen Test. Methods The clinical performance of Roche SARS-CoV-2 Rapid Antigen Test was evaluated vs. a reverse transcription polymerase chain reaction (RT-PCR) laboratory-based assay (Seegene AllplexTM2019-nCoV) in nasopharyngeal swabs collected from a series of consecutive patients referred for SARS-CoV-2 diagnostics to the Pederzoli Hospital (Peschiera del Garda, Verona, Italy) over a 2-week period. Results The final study population consisted of 321 consecutive patients (mean age, 46 years and IQR, 32–56 years; 181 women, 56.4%), with 149/321 (46.4%) positive for SARS-CoV-2 RNA via the Seegene AllplexTM2019-nCoV Assay, and 109/321 (34.0%) positive with Roche SARS-CoV-2 Rapid Antigen Test, respectively. The overall accuracy of Roche SARS-CoV-2 Rapid Antigen Test compared to molecular testing was 86.9%, with 72.5% sensitivity and 99.4% specificity. Progressive decline in performance was observed as cycle threshold (Ct) values of different SARS-CoV-2 gene targets increased. The sensitivity was found to range between 97–100% in clinical samples with Ct values <25, between 50–81% in those with Ct values between 25 and <30, but low as 12–18% in samples with Ct values between 30 and <37. Conclusions The clinical performance of Roche SARS-CoV-2 Rapid Antigen Test is excellent in nasopharyngeal swabs with Ct values <25, which makes it a reliable screening test in patients with high viral load. However, mass community screening would require the use of more sensitive techniques.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shan Wei ◽  
Esther Kohl ◽  
Alexandre Djandji ◽  
Stephanie Morgan ◽  
Susan Whittier ◽  
...  

AbstractThe COVID-19 pandemic has resulted in an urgent need for a rapid, point of care diagnostic testing that could be rapidly scaled on a worldwide level. We developed and tested a highly sensitive and robust assay based on reverse transcription loop mediated isothermal amplification (RT-LAMP) that uses readily available reagents and a simple heat block using contrived spike-in and actual clinical samples. RT-LAMP testing on RNA-spiked samples showed a limit of detection (LoD) of 2.5 copies/μl of viral transport media. RT-LAMP testing directly on clinical nasopharyngeal swab samples in viral transport media had an 85% positive percentage agreement (PPA) (17/20), and 100% negative percentage agreement (NPV) and delivered results in 30 min. Our optimized RT-LAMP based testing method is a scalable system that is sufficiently sensitive and robust to test for SARS-CoV-2 directly on clinical nasopharyngeal swab samples in viral transport media in 30 min at the point of care without the need for specialized or proprietary equipment or reagents. This cost-effective and efficient one-step testing method can be readily available for COVID-19 testing world-wide, especially in resource poor settings.


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