Search results for: biomarker detection

Authors: G. Eom, H. Kim, A. Hwang, T. Kang, B. Kim

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Telomerase activity is overexpressed in over 85% of human cancers while suppressed in normal somatic cells. Telomerase has been attracted as a universal cancer biomarker. Therefore, the development of effective telomerase activity detection methods is urgently demanded in cancer diagnosis and therapy. Herein, we report a nanogap-rich Au nanowire (NW) surface-enhanced Raman scattering (SERS) sensor for detection of human telomerase activity. The nanogap-rich Au NW SERS sensors were prepared simply by uniformly depositing nanoparticles (NPs) on single-crystalline Au NWs. We measured SERS spectra of methylene blue (MB) from 60 different nanogap-rich Au NWs and obtained the relative standard deviation (RSD) of 4.80%, confirming the superb reproducibility of nanogap-rich Au NW SERS sensors. The nanogap-rich Au NW SERS sensors enable us to detect telomerase activity in 0.2 cancer cells/mL. Furthermore, telomerase activity is detectable in 7 different cancer cell lines whereas undetectable in normal cell lines, which suggest the potential applicability of nanogap-rich Au NW SERS sensor in cancer diagnosis. We expect that the present nanogap-rich Au NW SERS sensor can be useful in biomedical applications including a diverse biomarker sensing.

Keywords: cancer biomarker, nanowires, surface-enhanced Raman scattering, telomerase

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Authors: Ki-Yeo Kim

Abstract:

Trends in genetics are transforming in order to identify differential coexpressions of correlated gene expression rather than the significant individual gene. Moreover, it is known that a combined biomarker pattern improves the discrimination of a specific cancer. The identification of the combined biomarker is also necessary for the early detection of invasive oral squamous cell carcinoma (OSCC). To identify the combined biomarker that could improve the discrimination of OSCC, we explored an appropriate number of genes in a combined gene set in order to attain the highest level of accuracy. After detecting a significant gene set, including the pre-defined number of genes, a combined expression was identified using the weights of genes in a gene set. We used the Principal Component Analysis (PCA) for the weight calculation. In this process, we used three public microarray datasets. One dataset was used for identifying the combined biomarker, and the other two datasets were used for validation. The discrimination accuracy was measured by the out-of-bag (OOB) error. There was no relation between the significance and the discrimination accuracy in each individual gene. The identified gene set included both significant and insignificant genes. One of the most significant gene sets in the classification of normal and OSCC included MMP1, SOCS3 and ACOX1. Furthermore, in the case of oral dysplasia and OSCC discrimination, two combined biomarkers were identified. The combined genomic expression achieved better performance in the discrimination of different conditions than in a single significant gene. Therefore, it could be expected that accurate diagnosis for cancer could be possible with a combined biomarker.

Keywords: oral squamous cell carcinoma, combined biomarker, microarray dataset, correlated genes

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Authors: Tania Vasquez Mata, Luis A. Herrera, Cristian Arriaga Canon

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Background: Locally advanced breast cancer of the luminal B phenotype, poses challenges due to its variable response to neoadjuvant chemotherapy. A predictive biomarker is needed to identify patients who will not respond to treatment, allowing for alternative therapies. This study aims to validate the use of the lncRNA GATA3-AS1, as a predictive biomarker using RNA in situ hybridization. Research aim: The aim of this study is to determine if GATA3-AS1 can serve as a biomarker for resistance to neoadjuvant chemotherapy in patients with locally advanced luminal B breast cancer. Methodology: The study utilizes RNA in situ hybridization with predesigned probes for GATA3-AS1 on Formalin-Fixed Paraffin-Embedded tissue sections. The samples underwent pretreatment and protease treatment to enable probe penetration. Chromogenic detection and signal evaluation were performed using specific criteria. Findings: Patients who did not respond to neoadjuvant chemotherapy showed a 3+ score for GATA3-AS1, while those who had a complete response had a 1+ score. Theoretical importance: This study demonstrates the potential clinical utility of GATA3-AS1 as a biomarker for resistance to neoadjuvant chemotherapy. Identifying non-responders early on can help avoid unnecessary treatment and explore alternative therapy options. Data collection and analysis procedures: Tissue samples from patients with locally advanced luminal B breast cancer were collected and processed using RNA in situ hybridization. Signal evaluation was conducted under a microscope, and scoring was based on specific criteria. Questions addressed: Can GATA3-AS1 serve as a predictive biomarker for neoadjuvant chemotherapy response in locally advanced luminal B breast cancer? Conclusion: The lncRNA GATA3-AS1 can be used as a biomarker for resistance to neoadjuvant chemotherapy in patients with locally advanced luminal B breast cancer. Its identification through RNA in situ hybridization of tissue obtained from the initial biopsy can aid in treatment decision-making.

Keywords: biomarkers, breast neoplasms, genetics, neoadjuvant therapy, tumor

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Authors: Ji Su Kim, Bo Ram Choi, Ju Yeon Cho, Hyukjin Lee

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Epidermal growth factor receptor (EGFR) 19 deletion mutation gene is over-expressed in carcinoma patient. EGFR 19 deletion mutation is known as typical biomarker of non-small cell lung cancer (NSCLC), which one section in the coding exon 19 of EGFR is deleted. Therefore, there have been many attempts over the years to detect EGFR 19 deletion mutation for replacing conventional diagnostic method such as PCR and tissue biopsy. We developed a simple and facile detection platform based on Rolling Circle Amplification (RCA), which provides highly amplified products in isothermal amplification of the ligated DNA template. Limit of detection (~50 nM) and a faster detection time (~30 min) could be achieved by introducing RCA.

Keywords: EGFR19, cancer, diagnosis, rolling circle amplification (RCA), hydrogel

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Authors: Ying Li, Rui Hu, Shizhen Chen, Xin Zhou, Yunhuang Yang

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Prostate cancer is one of the leading causes of cancer-related death among men. Prostate-specific antigen (PSA), a specific product of prostatic epithelial cells, is an important indicator of prostate cancer. Though PSA is not a specific serum biomarker for the screening of prostate cancer, it is recognized as an indicator for prostate cancer recurrence and response to therapy for patient’s post-prostatectomy. Since radical prostatectomy eliminates the source of PSA production, serum PSA levels fall below 50 pg/mL, and may be below the detection limit of clinical immunoassays (current clinical immunoassay lower limit of detection is around 10 pg/mL). Many clinical studies have shown that intervention at low PSA levels was able to improve patient outcomes significantly. Therefore, ultra-sensitive and precise assays that can accurately quantify extremely low levels of PSA (below 1-10 pg/mL) will facilitate the assessment of patients for the possibility of early adjuvant or salvage treatment. Currently, the commercially available ultra-sensitive ELISA kit (not used clinically) can only reach a detection limit of 3-10 pg/mL. Other platforms developed by different research groups could achieve a detection limit as low as 0.33 pg/mL, but they relied on sophisticated instruments to get the final readout. Herein we report a microfluidic platform for point-of-care (POC) detection of PSA with a detection limit of 0.5 pg/mL and without the assistance of any equipment. This platform is based on a previously reported volumetric-bar-chart chip (V-Chip), which applies platinum nanoparticles (PtNPs) as the ELISA probe to convert the biomarker concentration to the volume of oxygen gas that further pushes the red ink to form a visualized bar-chart. The length of each bar is used to quantify the biomarker concentration of each sample. We devised a long reading channel V-Chip (LV-Chip) in this work to achieve a wide detection window. In addition, LV-Chip employed a unique enzyme-free ELISA probe that enriched PtNPs significantly and owned 500-fold enhanced catalytic ability over that of previous V-Chip, resulting in a significantly improved detection limit. LV-Chip is able to complete a PSA assay for five samples in 20 min. The device was applied to detect PSA in 50 patient serum samples, and the on-chip results demonstrated good correlation with conventional immunoassay. In addition, the PSA levels in finger-prick whole blood samples from healthy volunteers were successfully measured on the device. This completely stand-alone LV-Chip platform enables convenient POC testing for patient follow-up in the physician’s office and is also useful in resource-constrained settings.

Keywords: point-of-care detection, microfluidics, PSA, ultra-sensitive

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Authors: Yalda Zarnegarnia, Shari Messinger

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Receiver operating characteristic (ROC) curves have been widely used in medical research to illustrate the performance of the biomarker in correctly distinguishing the diseased and non-diseased groups. Correlated biomarker data arises in study designs that include subjects that contain same genetic or environmental factors. The information about correlation might help to identify family members at increased risk of disease development, and may lead to initiating treatment to slow or stop the progression to disease. Approaches appropriate to a case-control design matched by family identification, must be able to accommodate both the correlation inherent in the design in correctly estimating the biomarker’s ability to differentiate between cases and controls, as well as to handle estimation from a matched case control design. This talk will review some developed methods for ROC curve estimation in settings with correlated data from case control design and will discuss the limitations of current methods for analyzing correlated familial paired data. An alternative approach using Conditional ROC curves will be demonstrated, to provide appropriate ROC curves for correlated paired data. The proposed approach will use the information about the correlation among biomarker values, producing conditional ROC curves that evaluate the ability of a biomarker to discriminate between diseased and non-diseased subjects in a familial paired design.

Keywords: biomarker, correlation, familial paired design, ROC curve

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Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

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MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

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Authors: Hwang Ahreum, Kang Taejoon, Kim Bongsoo

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Nanosensors for high sensitive detection of diseases have been widely studied to improve the quality of life. Here, we suggest robust nano-plasmonic diagnostic sensor using cysteine tagged protein G (Cys3-protein G) and ultraflat, ultraclean and single-crystalline Au nanoplates. Protein G formed on an ultraflat Au surface provides ideal background for dense and uniform immobilization of antibodies. The Au is highly stable in diverse biochemical environment and can immobilize antibodies easily through Au-S bonding, having been widely used for various biosensing applications. Especially, atomically smooth single-crystalline Au nanomaterials synthesized using chemical vapor transport (CVT) method are very suitable to fabricate reproducible sensitive sensors. As the C-reactive protein (CRP) is a nonspecific biomarker of inflammation and infection, it can be used as a predictive or prognostic marker for various cardiovascular diseases. Cys3-protein G immobilized uniformly on the Au nanoplate enable CRP antibody (anti-CRP) to be ordered in a correct orientation, making their binding capacity be maximized for CRP detection. Immobilization condition for the Cys3-protein G and anti-CRP on the Au nanoplate is optimized visually by AFM analysis. Au nanoparticle - Au nanoplate (NPs-on-Au nanoplate) assembly fabricated from sandwich immunoassay for CRP can reduce zero-signal extremely caused by nonspecific bindings, providing a distinct surface-enhanced Raman scattering (SERS) enhancement still in 10-18 M of CRP concentration. Moreover, the NP-on-Au nanoplate sensor shows an excellent selectivity against non-target proteins with high concentration. In addition, comparing with control experiments employing a Au film fabricated by e-beam assisted deposition and linker molecule, we validate clearly contribution of the Au nanoplate for the attomolar sensitive detection of CRP. We expect that the devised platform employing the complex of single-crystalline Au nanoplates and Cys3-protein G can be applied for detection of many other cancer biomarkers.

Keywords: Au nanoplate, biomarker, diagnostic sensor, protein G, SERS

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Authors: Lucia Salvioni, Pietro Giorgio Lovaglio, Valerio Leoni, Miriam Colombo, Luisa Fiandra

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The involvement of plasmatic surfactant protein-D (SP-D) in pulmonary diseases has been long investigated, and over the last two years, more interest has been directed to determine its role as a marker of COVID-19. In this direction, several studies aimed to correlate pulmonary surfactant proteins with the clinical manifestations of the virus indicated SP-D as a prognostic biomarker of COVID-19 pneumonia severity. The present work has performed a retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio (Lombardia, Italy) with the aim to assess differences in the hematic SP-D concentrations among COVID-19 patients and healthy donors and the role of SP-D as a prognostic marker of severity and/or of mortality risk. The obtained results showed a significant difference in the mean of log SP-D levels between COVID-19 patients and healthy donors, so as between dead and survived patients. SP-D values were significantly higher for both hospitalized COVID-19 and dead patients, with threshold values of 150 and 250 ng/mL, respectively. SP-D levels at admission and increasing differences among follow-up and admission values resulted in the strongest significant risk factors of mortality. Therefore, this study demonstrated the role of SP-D as a predictive marker of SARS-CoV-2 infection and its outcome. A significant correlation of SP-D with patient mortality indicated that it is also a prognostic factor in terms of mortality, and its early detection should be considered to design adequate preventive treatments for COVID-19 patients.

Keywords: SARS-CoV-2 infection, COVID-19, surfactant protein-D (SP-D), mortality, biomarker

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Authors: Supannika Klangphukhiew, Roongnapa Srichana, Rina Patramanon

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Cortisol has been used as a well-known commercial stress biomarker. A homeostasis response to psychological stress is indicated by an increased level of cortisol produced in hypothalamus-pituitary-adrenal (HPA) axis. Chronic psychological stress contributing to the high level of cortisol relates to several health problems. In this study, the cortisol biosensor was fabricated that mimicked the natural receptors. The artificial antibodies were prepared using molecular imprinted polymer technique that can imitate the performance of natural anti-cortisol antibody with high stability. Cortisol-molecular imprinted polymer (cortisol-MIP) was obtained using the multi-step swelling and polymerization protocol with cortisol as a target molecule combining methacrylic acid:acrylamide (2:1) with bisacryloyl-1,2-dihydroxy-1,2-ethylenediamine and ethylenedioxy-N-methylamphetamine as cross-linkers. Cortisol-MIP was integrated to the sensor. It was coated on the disposable screen-printed carbon electrode (SPCE) for portable electrochemical analysis. The physical properties of Cortisol-MIP were characterized by means of electron microscope techniques. The binding characteristics were evaluated via covalent patterns changing in FTIR spectra which were related to voltammetry response. The performance of cortisol-MIP modified SPCE was investigated in terms of detection range, high selectivity with a detection limit of 1.28 ng/ml. The disposable cortisol biosensor represented an application of MIP technique to recognize steroids according to their structures with feasibility and cost-effectiveness that can be developed to use in point-of-care.

Keywords: stress biomarker, cortisol, molecular imprinted polymer, screen-printed carbon electrode

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Authors: Shveta Bathla, Preeti Rawat, Sudarshan Kumar, Rubina Baithalu, Jogender Singh Rana, Tushar Kumar Mohanty, Ashok Kumar Mohanty

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Pregnancy is a complex process which includes series of events such as fertilization, formation of blastocyst, implantation of embryo, placental formation and development of fetus. The success of these events depends on various interactions which are synchronized by endocrine interaction between a receptive dam and competent embryo. These interactions lead to change in expression of hormones and proteins. But till date no protein biomarker is available which can be used to detect successful completion of these events. We employed quantitative proteomics approach to develop putative serological biomarker which has diagnostic applicability for early detection of pregnancy in cows. For this study, sera were collected from control (non-pregnant, n=6) and pregnant animals on successive days of pregnancy (7, 19, 45, n=6). The sera were subjected to depletion for removal of albumin using Norgen depletion kit. The tryptic peptides were labeled with iTRAQ. The peptides were pooled and fractionated using bRPLC over 80 min gradient. Then 12 fractions were injected to nLC for identification and quantitation in DDA mode using ESI. Identification using Mascot search revealed 2056 proteins out of which 352 proteins were differentially expressed. Twenty proteins were upregulated and twelve proteins were down-regulated with fold change > 1.5 and < 0.6 respectively (p < 0.05). The gene ontology studies of DEPs using Panther software revealed that majority of proteins are actively involved in catalytic activities, binding and enzyme regulatory activities. The DEP'S such as NF2, MAPK, GRIPI, UGT1A1, PARP, CD68 were further subjected to pathway analysis using KEGG and Cytoscape plugin Cluego that showed involvement of proteins in successful implantation, maintenance of pluripotency, regulation of luteal function, differentiation of endometrial macrophages, protection from oxidative stress and developmental pathways such as Hippo. Further efforts are continuing for targeted proteomics, western blot to validate potential biomarkers and development of diagnostic kit for early pregnancy diagnosis in cows.

Keywords: bRPLC, Cluego, ESI, iTRAQ, KEGG, Panther

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Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

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Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

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Authors: Marija Knez, James C.R. Stangoulis, Manja Zec, Zoran Pavlovic, Jasmina D. Martacic, Mirjana Gurinovic, Maria Glibetic

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Background: Zinc is an essential micronutrient for humans with important physiological functions. A sensitive and specific biomarker for assessing Zn status is still needed. Objective: The major aim of this study was to examine if the changes in the content of plasma phospholipid LA, DGLA and LA: DGLA ratio can be used to efficiently predict the dietary Zn intake and plasma Zn status of humans. Methods: The study was performed on apparently healthy human volunteers. The dietary Zn intake was assessed using 24h recall questionnaires. Plasma phospholipid fatty acid analysis was done by gas chromatography and plasma analysis of minerals by atomic absorption spectrometry. Biochemical, anthropometrical and hematological parameters were assessed. Results: No significant relationship was found between the dietary and plasma zinc status (r=0.07; p=0.6). There is a statistically significant correlation between DGLA and plasma Zn (r=0.39, p=0.00). No relationship was observed between the linoleic acid and plasma Zn, while there was a significant negative correlation between LA: DGLA ratio and plasma Zn status (r=-0.35, p=0.01). Similarly, there were statistically significant difference in DGLA status (p=0.004) and LA: DGLA ratio (p=0.042) between the Zn formed groups. Conclusions: This study is an initial step in evaluating LA: DGLA ratio as a biomarker of Zn status in humans. The results are encouraging as they show that concentration of DGLA is decreased and LA: DGLA ratio increased in people with lower dietary Zn intake. However, additional studies are needed to fully examine the sensitivity of this biomarker.

Keywords: dietary Zn intake Zinc, fatty acid composition, LA: DGLA, healthy population, plasma Zn status, Zn biomarker

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Authors: M. G. R. S. Perera, B. S. Weerakoon, L. P. G. Sherminie, M. L. Jayatilake, R. D. Jayasinghe, W. Huang

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The aim of this study was to measure and evaluate the Longitudinal Relaxation Times (T1) in bone marrow of an Acute Myeloid Leukaemia (AML) patient in order to explore the potential for a prognostic biomarker using Magnetic Resonance Imaging (MRI) which will be a non-invasive prognostic approach to AML. MR image data were collected in the DICOM format and MATLAB Simulink software was used in the image processing and data analysis. For quantitative MRI data analysis, Region of Interests (ROI) on multiple image slices were drawn encompassing vertebral bodies of L3, L4, and L5. T1 was evaluated using the T1 maps obtained. The estimated bone marrow mean value of T1 was 790.1 (ms) at 3T. However, the reported T1 value of healthy subjects is significantly (946.0 ms) higher than the present finding. This suggests that the T1 for bone marrow can be considered as a potential prognostic biomarker for AML patients.

Keywords: acute myeloid leukaemia, longitudinal relaxation time, magnetic resonance imaging, prognostic biomarker.

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Authors: Mohamed Hrouda

Abstract:

The Principal Component Analysis (PCA) was performed on a dataset comprising 41 biomarker concentrations from twenty-three core source rocks samples and seven oil samples from different location, with the objective of establishing the major sources of variance within the steranes, tricyclic terpanes, hopanes, and triaromatic steroid. This type of analysis can be used as an aid when deciding which molecular biomarker maturity, source facies or depositional environment parameters should be plotted, because the principal component loadings plots tend to extract the biomarker variables related to maturity, source facies or depositional environment controls. Facies characterization of the source rock samples separate the Silurian and Devonian source rock samples into three groups. Maturity evaluation of source rock samples based on biomarker and aromatic hydrocarbon distributions indicates that not all the samples are strongly affected by maturity, the Upper Devonian samples from wells located in the northern part of the basin are immature, whereas the other samples which have been selected from the Lower Silurian are mature and have reached the main stage of the oil window, the Lower Silurian source rock strata revealed a trend of increasing maturity towards the south and southwestern part of Ghadames Basin. Most of the facies-based parameters employed in this project using biomarker distributions clearly separate the oil samples into three groups. Group I contain oil samples from wells within Al-Wafa oil field Located in the south western part of the basin, Group II contains oil samples collected from Al-Hamada oil field complex in the south and the third group contains oil samples collected from oil fields located in the north

Keywords: Ghadamis basin, geochemistry, silurian, devonian

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Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman

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Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.

Keywords: stem cells, leukemia, biomarkers, flow cytometry

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Authors: Soledad Carinelli, Iñigo Fernández, José Luis González-Mora, Pedro A. Salazar-Carballo

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Mastitis is the most relevant inflammatory disease in cattle, affecting the animal health and causing important economic losses on dairy farms. This disease takes place in the mammary gland or udder when some opportunistic microorganisms, such as Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium bovis, etc., invade the teat canal. According to the severity of the inflammation, mastitis can be classified as sub-clinical, clinical and chronic. Standard methods for mastitis detection include counts of somatic cells, cell culture, electrical conductivity of the milk, and California test (evaluation of “gel-like” matrix consistency after cell lysed with detergents). However, these assays present some limitations for accurate detection of subclinical mastitis. Currently, haptoglobin, an acute phase protein, has been proposed as novel and effective biomarker for mastitis detection. In this work, an electrochemical biosensor based on polydopamine-modified magnetic nanoparticles (MNPs@pDA) for haptoglobin detection is reported. Thus, MNPs@pDA has been synthesized by our group and functionalized with hemoglobin due to its high affinity to haptoglobin protein. The protein was labeled with specific antibodies modified with alkaline phosphatase enzyme for its electrochemical detection using an electroactive substrate (1-naphthyl phosphate) by differential pulse voltammetry. After the optimization of assay parameters, the haptoglobin determination was evaluated in milk. The strategy presented in this work shows a wide range of detection, achieving a limit of detection of 43 ng/mL. The accuracy of the strategy was determined by recovery assays, being of 84 and 94.5% for two Hp levels around the cut off value. Milk real samples were tested and the prediction capacity of the electrochemical biosensor was compared with a Haptoglobin commercial ELISA kit. The performance of the assay has demonstrated this strategy is an excellent and real alternative as screen method for sub-clinical bovine mastitis detection.

Keywords: bovine mastitis, haptoglobin, electrochemistry, magnetic nanoparticles, polydopamine

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Authors: Jae-Jeong Kim, Ki-Ro Kim, Hyoung-Kyu Song

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In this paper, we propose an efficient signal detector that switches M parameter of QRD-M detection scheme is proposed for MIMO-OFDM system. The proposed detection scheme calculates the threshold by 1-norm condition number and then switches M parameter of QRD-M detection scheme according to channel information. If channel condition is bad, the parameter M is set to high value to increase the accuracy of detection. If channel condition is good, the parameter M is set to low value to reduce complexity of detection. Therefore, the proposed detection scheme has better trade off between BER performance and complexity than the conventional detection scheme. The simulation result shows that the complexity of proposed detection scheme is lower than QRD-M detection scheme with similar BER performance.

Keywords: MIMO-OFDM, QRD-M, channel condition, BER

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Authors: Jae-Hyun Ro, Yong-Jun Kim, Chang-Bin Ha, Hyoung-Kyu Song

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In multiple input multiple output-orthogonal frequency division multiplexing (MIMO-OFDM) systems, many detection schemes have been developed to improve the error performance and to reduce the complexity. Maximum likelihood (ML) detection has optimal error performance but it has very high complexity. Thus, this paper proposes reduced complexity of ML detection combined with decision feedback equalizer (DFE). The error performance of the proposed detection scheme is higher than the conventional DFE. But the complexity of the proposed scheme is lower than the conventional ML detection.

Keywords: detection, DFE, MIMO-OFDM, ML

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Authors: Marwa I. Shabayek, Ola A. Said, Hanan A. Attaia, Heba A. Awida

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Bladder carcinoma is an important worldwide health problem. Both cystoscopy and urine cytology used in detecting bladder cancer suffer from drawbacks where cystoscopy is an invasive method and urine cytology shows low sensitivity in low grade tumors. This study validates easier and less time-consuming techniques to evaluate the value of combined use of angiogenin and clusterin in comparison and combination with voided urine cytology in the detection of bladder cancer patients. This study includes malignant (bladder cancer patients, n= 50), benign (n=20), and healthy (n=20) groups. The studied groups were subjected to cystoscopic examination, detection of bilharzial antibodies, urine cytology, and estimation of urinary angiogenin and clusterin by ELISA. The overall sensitivity and specifcity were 66% and 75% for angiogenin, 70% and 82.5% for clusterin and 46% and 80% for voided urine cytology. Combined sensitivity of angiogenin and clusterin with urine cytology increased from 82 to 88%.

Keywords: angiogenin, bladder cancer, clusterin, cytology

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Authors: Josselyn Mata Calidonio, Arianna I. Maddox, Kimberly Hamad-Schifferli

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Rapid diagnostics are critical infectious disease tools that are designed to detect a known biomarker using antibodies specific to that biomarker. However, a way to detect unknown viruses has not yet been achieved in a paper test format. We describe here a route to make an adaptable paper immunoassay that can detect an unknown biomarker, demonstrating it on SARS-CoV-2 variants. The immunoassay repurposes cross-reactive antibodies raised against the alpha variant. Gold nanoparticles of two different colors conjugated to two different antibodies create a colorimetric signal, and machine learning of the resulting colorimetric pattern is used to train the assay to discriminate between variants of alpha and Omicron BA.5. By using principal component analysis, the colorimetric test patterns can pick up and discriminate an unknown that it has not encountered before, Omicron BA.1. The test has an accuracy of 100% and a potential calculated discriminatory power of 900. We show that it can be used adaptively and that it can be used to pick up emerging variants without the need to raise new antibodies.

Keywords: adaptive immunoassay, detecting unknown viruses, gold nanoparticles, paper immunoassay, repurposing antibodies

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Authors: M. Salvador, J. C. Martinez-Garcia, A. Moyano, M. C. Blanco-Lopez, M. Rivas

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Biosensors play a crucial role in the detection of molecules nowadays due to their advantages of user-friendliness, high selectivity, the analysis in real time and in-situ applications. Among them, Lateral Flow Immunoassays (LFIAs) are presented among technologies for point-of-care bioassays with outstanding characteristics such as affordability, portability and low-cost. They have been widely used for the detection of a vast range of biomarkers, which do not only include proteins but also nucleic acids and even whole cells. Although the LFIA has traditionally been a positive/negative test, tremendous efforts are being done to add to the method the quantifying capability based on the combination of suitable labels and a proper sensor. One of the most successful approaches involves the use of magnetic sensors for detection of magnetic labels. Bringing together the required characteristics mentioned before, our research group has developed a biosensor to detect biomolecules. Superparamagnetic nanoparticles (SPNPs) together with LFIAs play the fundamental roles. SPMNPs are detected by their interaction with a high-frequency current flowing on a printed micro track. By means of the instant and proportional variation of the impedance of this track provoked by the presence of the SPNPs, quantitative and rapid measurement of the number of particles can be obtained. This way of detection requires no external magnetic field application, which reduces the device complexity. On the other hand, the major limitations of LFIAs are that they are only qualitative or semiquantitative when traditional gold or latex nanoparticles are used as color labels. Moreover, the necessity of always-constant ambient conditions to get reproducible results, the exclusive detection of the nanoparticles on the surface of the membrane, and the short durability of the signal are drawbacks that can be advantageously overcome with the design of magnetically labeled LFIAs. The approach followed was to coat the SPIONs with a specific monoclonal antibody which targets the protein under consideration by chemical bonds. Then, a sandwich-type immunoassay was prepared by printing onto the nitrocellulose membrane strip a second antibody against a different epitope of the protein (test line) and an IgG antibody (control line). When the sample flows along the strip, the SPION-labeled proteins are immobilized at the test line, which provides magnetic signal as described before. Preliminary results using this practical combination for the detection and quantification of the Prostatic-Specific Antigen (PSA) shows the validity and consistency of the technique in the clinical range, where a PSA level of 4.0 ng/mL is the established upper normal limit. Moreover, a LOD of 0.25 ng/mL was calculated with a confident level of 3 according to the IUPAC Gold Book definition. Its versatility has also been proved with the detection of other biomolecules such as troponin I (cardiac injury biomarker) or histamine.

Keywords: biosensor, lateral flow immunoassays, point-of-care devices, superparamagnetic nanoparticles

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Authors: Lixin Pei, Zhilong Huang, Wenzhe Gang

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Organic geochemistry of source rocks and oils in the Nanpu Sag, Bohai Bay basin was studied on the basis of the results of Rock-Eval and biomarker. The possible source rocks consist of the third member (Es₃) and the first member (Es₁) of Shahejie formation and the third member of Dongying Formation (Ed₃) in the Nanpu Sag. The Es₃, Es₁, and Ed₃ source rock intervals in the Nanpu Sag all have high organic-matter richness and are at hydrocarbon generating stage, which are regarded as effective source rocks. The three possible source rock intervals have different biomarker associations and can be differentiated by gammacerane/αβ C₃₀ hopane, ETR ([C₂₈+C₂₉]/ [C₂₈+C₂₉+Ts]), C₂₇ diasterane/sterane and C₂₇/C₂₉ steranes, which suggests they deposited in different environments. Based on the oil-source rock correlation, the shallow oils mainly originated from the Es₃ and Es₁ source rocks in the Nanpu Sag. Through hydrocarbon generation and expulsion history of the source rocks, trap development history and accumulation history, the shallow oils mainly originated from paleo-reservoirs in the Es₃ and Es₁ during the period of Neotectonism, and the residual paleo-reservoirs in the Es₃ and Es₁ would be the focus targets in the Nanpu Sag; Bohai Bay Basin.

Keywords: source rock, biomarker association, Nanpu Sag, Bohai Bay Basin

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Authors: Suveen Kumar

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Oral cancer (OC) is the sixth most death causing cancer in world which includes tumour of lips, floor of the mouth, tongue, palate, cheeks, sinuses, throat, etc. Conventionally, the techniques used for OC detection are toluidine blue staining, biopsy, liquid-based cytology, visual attachments, etc., however these are limited by their highly invasive nature, low sensitivity, time consumption, sophisticated instrument handling, sample processing and high cost. Therefore, we developed biosensing chips for non-invasive detection of OC via CYFRA-21-1 biomarker. CYFRA-21-1 (molecular weight: 40 kDa) is secreted in saliva of OC patients which is a non-invasive biological fluid with a cut-off value of 3.8 ng mL-1, above which the subjects will be suffering from oral cancer. Therefore, in first work, 3-aminopropyl triethoxy silane (APTES) functionalized zirconia (ZrO2) nanoparticles (APTES/nZrO2) were used to successfully detect CYFRA-21-1 in a linear detection range (LDR) of 2-16 ng mL-1 with sensitivity of 2.2 µA mL ng-1. Successively, APTES/nZrO2-RGO was employed to prevent agglomeration of ZrO2 by providing high surface area reduced graphene oxide (RGO) support and much wider LDR (2-22 ng mL-1) was obtained with remarkable limit of detection (LOD) as 0.12 ng mL-1. Further, APTES/nY2O3/ITO platform was used for oral cancer bioseneor development. The developed biosensor (BSA/anti-CYFRA-21-1/APTES/nY2O3/ITO) have wider LDR (0.01-50 ng mL-1) with remarkable limit of detection (LOD) as 0.01 ng mL-1. To improve the sensitivity of the biosensing platform, nanocomposite of yattria stabilized nanostructured zirconia-reduced graphene oxide (nYZR) based biosensor has been developed. The developed biosensing chip having ability to detect CYFRA-21-1 biomolecules in the range of 0.01-50 ng mL-1, LOD of 7.2 pg mL-1 with sensitivity of 200 µA mL ng-1. Further, the applicability of the fabricated biosensing chips were also checked through real sample (saliva) analysis of OC patients and the obtained results showed good correlation with the standard protein detection enzyme linked immunosorbent assay (ELISA) technique.

Keywords: non-invasive, oral cancer, nanomaterials, biosensor, biochip

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Authors: Yishu Gong, Liangliang Yang, Jianyu Zhang, Zhengyu Chen, Sihong He, Xusheng Zhang, Wei Zhang

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide and is characterized by cognitive decline and behavioral changes. People living with Alzheimer’s disease often find it hard to complete routine tasks. However, there are limited objective assessments that aim to quantify the difficulty of certain tasks for AD patients compared to non-AD people. In this study, we propose to use speech emotion recognition (SER), especially the frustration level, as a potential biomarker for quantifying the difficulty patients experience when describing a picture. We build an SER model using data from the IEMOCAP dataset and apply the model to the DementiaBank data to detect the AD/non-AD group difference and perform longitudinal analysis to track the AD disease progression. Our results show that the frustration level detected from the SER model can possibly be used as a cost-effective tool for objective tracking of AD progression in addition to the Mini-Mental State Examination (MMSE) score.

Keywords: Alzheimer’s disease, speech emotion recognition, longitudinal biomarker, machine learning

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Authors: Wei Li, Tuo Yang

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In order to satisfy the real-time and accurate requirements of cigarette smoke detection in complex scenes, a cigarette smoke detection technology based on the combination of deep learning and color features was proposed. Firstly, based on the color features of cigarette smoke, the suspicious cigarette smoke area in the image is extracted. Secondly, combined with the efficiency of cigarette smoke detection and the problem of network overfitting, a network model for cigarette smoke detection was designed according to YOLOV3 algorithm to reduce the false detection rate. The experimental results show that the method is feasible and effective, and the accuracy of cigarette smoke detection is up to 99.13%, which satisfies the requirements of real-time cigarette smoke detection in complex scenes.

Keywords: deep learning, computer vision, cigarette smoke detection, YOLOV3, color feature extraction

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Authors: Doaa Hashad, Amany Elbanna, Abeer Ibrahim, Gihan Khedr

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Background: H19 is one of the long non coding RNAs (LncRNA) that is related to the progression of many diseases including cancers. This work was carried out to study the level of the long non-coding RNA; H119, in plasma of patients with gastric cancer (GC) and to assess its significance in their clinical management. Methods: A total of sixty-two participants were enrolled in the present study. The first group included thirty-two GC patients, while the second group was formed of thirty age and sex matched healthy volunteers serving as a control group. Plasma samples were used to assess H19 gene expression using real time quantitative PCR technique. Results: H19 expression was up-regulated in GC patients with positive correlation to TNM cancer stages. Conclusions: Up-regulation of H19 is closely associated with gastric cancer and correlates well with tumor staging. Convenient, efficient quantification of H19 in plasma using real time PCR technique implements its role as a potential noninvasive prognostic biomarker in gastric cancer, that predicts patient’s outcome and most importantly as a novel target in gastric cancer treatment with better performance achieved on using both CEA and H19 simultaneously.

Keywords: biomarker, gastric, cancer, LncRNA

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Authors: Nessrine Jebari, Elisabeth Dufour-Gergam, Mehdi Ammar

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This work outlines the development and characterization of a microfluidic immunosensor, designed for real-time monitoring of proinflammatory pathologies, within the domain of biomedical diagnostics. The key focus of this research is the microfabrication protocol developed in a cleanroom environment, emphasizing the intricate processes employed in the fabrication of this sophisticated biosensor. The principal contribution of this project is grounded in the application of COMSOL Multiphysics for detailed three-dimensional simulations, which are instrumental in the development of a patch-like device designed for non-invasive monitoring of biomarkers in sweat. The device integrates a distinctive combination of magnetofluidic manipulation and capacitive sensing approaches, thereby enhancing the standard in biomarker detection and quantification. A pivotal aspect of our device is its use of biomarker-tagged magnetic nanoparticles (MNPs), significantly enhancing sensitivity and multifunctionality. The immunosensor comprises two main units: the primary unit, featuring an array of serial microcoils for optimal MNP trapping and microfluidic mixing, and the secondary unit, a layered structure with a planar microcoil and two copper electrodes. This configuration forms a capacitor integral to the capacitive sensing capabilities of the device, allowing for precise quantification of biomarker-tagged MNPs. The microfabrication process, executed in a controlled cleanroom environment, involved the precise layering and structuring of microcoils and electrodes, along with the integration of a microfluidic platform. This meticulous process ensures high reproducibility and accuracy, critical for a reliable diagnostic tool. Experimental results exhibit the immunosensor's promoting sensing capabilities, with a sensitivity range of 60% to 75% at 70% MNP occupancy in the detection zone. This performance underscores the device's potential in overcoming the limitations of surface biochemical functionalization, a challenge in conventional biosensors. Beyond monitoring proinflammatory pathologies, the immunosensor's versatility extends to detecting a wide range of pathogens, including bacteria. Its compatibility with complementary screening techniques allows for the identification of multiple biomarkers, enhancing its utility in both clinical and research settings. Conclusion: In conclusion, the development of this microfluidic immunosensor marks a significant result in biomedical engineering and diagnostic technology. The microfabrication process, executed in a cleanroom environment, is crucial to the device's distinctive design and its multifunctional attributes. This technology not only progresses the realm of biomedical diagnostics but also paves the way for further exploration and development within the discipline. Its applications extend from early disease detection to the monitoring of treatment effectiveness.

Keywords: COMSOL multiphysics 3D simulation, microfluidic immunosensor, magnetofluidic manipulation, magnetic nanoparticle trapping, laboratory-on-patch technology

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Authors: Jeonghun Lee

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In this study, we investigated the relationship between stress and thyroid dysfunction in such patients who underwent thyroidectomy. This study included 101 patients who underwent thyroidectomy from January 2015 to June 2020 and experienced hypothyroidism. The included patients had good drug compliance with the same dosage of levothyroxine (LT4). The male-to-female ratio was 1:4.6, and the mean age was 45.4 years at surgery and 50.2 years at stressful events. Eighteen patients underwent lobectomies and, of these, 12 did not take LT4. The mean follow-up period was 49(8-93) months. Statistical analyses were performed using the paired t-test, Wilcoxon signed-rank test, and McNemer test using PROC MIXED with SAS 9.4. Forty-five patients (44.6%) had hypothyroidism with thyroid-stimulating hormone (TSH) >10 μIU/mL. There was distress in 81 patients and eustress in 10 patients. TSH levels increased during a mean 5.8 months (min 1, max 12) in 24 patients who specified the date of their life events. Even though each patient took the same dose of LT4, when the patients were under stress, both the free T4 and T3 decreased and TSH increased, regardless of whether the patient experienced distress or eustress (P <0.001). While adjusting for the effect of the free T4 and T3, TSH increased significantly in the patients after stress (P <0.001). For patients with thyroid cancer who are simultaneously experiencing life events, TSH may be used as a stress biomarker to enable the implementation of appropriate treatment and counseling strategies.

Keywords: endocrine, thyroid, thyroid function, biomarker, stress

Procedia PDF Downloads 46

Authors: N. Othman, J. Ujang, M. N. Ismail, R. Noordin, B. H. Lim

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Amoebiasis is caused by the Entamoeba histolytica and still endemic in many parts of the tropical region, worldwide. Currently, there is no available vaccine against amoebiasis. Hence, there is an urgent need to develop a vaccine. The excretory secretory antigen (ESA) of E. histolytica is a suitable biomarker for the vaccine candidate since it can modulate the host immune response. Hence, the objective of this study is to identify the proteome of the ESA towards finding suitable biomarker for the vaccine candidate. The non-gel based and gel-based proteomics analyses were performed to identify proteins. Two kinds of mass spectrometry with different ionization systems were utilized i.e. LC-MS/MS (ESI) and MALDI-TOF/TOF. Then, the functional proteins classification analysis was performed using PANTHER software. Combination of the LC -MS/MS for the non-gel based and MALDI-TOF/TOF for the gel-based approaches identified a total of 273 proteins from the ESA. Both systems identified 29 similar proteins whereby 239 and 5 more proteins were identified by LC-MS/MS and MALDI-TOF/TOF, respectively. Functional classification analysis showed the majority of proteins involved in the metabolic process (24%), primary metabolic process (19%) and protein metabolic process (10%). Thus, this study has revealed the proteome the E. histolytica ESA and the identified proteins merit further investigations as a vaccine candidate.

Keywords: E. histolytica, ESA, proteomics, biomarker

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