Detection Of Tumor Biomarkers Research Articles

Click-response-driven high-speed and ultrasensitive electrochemical sensing interface: Addressing its accuracy challenge

For electrochemical sensors, maintaining accuracy while achieving sensitive detection is of paramount importance. The fixation of the signal substance as one of the main steps in the construction process of a sensor has a significant impact on the accuracy. Currently, physical and chemical methods are the primary approaches for the fixation of the signal substance, which have the following issues. The accuracy of a sensor may be affected by the instability resulting from the physical immobilization of the signal substance and the chemical immobilization process is typically time-consuming. To overcome these obstacles, the ultra-sensitive electrochemical sensing interface is constructed by click reaction to achieve accurate and rapid detection of tumor biomarkers. After the formation of immune-sandwich structure in a test tube, a large amount of ethynylferrocene (EFc) molecules in the Zeolitic imidazolate frameworks (ZIF-8) immunoprobe are released under acidic conditions, followed by covalently linking to the substrate within 6 minutes through a click reaction. Under optimal conditions, the electrochemical sensor had an ultralow detection limit of 32.90 fg mL−1 for the model analyte (CEA) with a wide detection range from 100 fg mL−1 to 100 ng mL−1. This work provides a new perspective for designing electrochemical sensors with excellent performance.

Enhancing electrochemical detection through machine learning-driven prediction for canine mammary tumor biomarker with green silver nanoparticles.

This study developed an innovative biosensor strategy for the sensitive and selective detection of canine mammary tumor biomarkers, cancer antigen 15-3 (CA 15-3) and mucin 1 (MUC-1), integrating green silver nanoparticles (GAgNPs) with machine learning (ML) algorithms to achieve high diagnostic accuracy and potential for noninvasive early detection. The GAgNPs-enhanced electrochemical biosensor demonstrated selective detection of CA 15-3 in serum and MUC-1 in tissue homogenates, with limits of detection (LODs) of 0.07 and 0.11 U mL-1, respectively. The nanoscale dimensions of the GAgNPs endowed them with electrochemically active surface areas, facilitating sensitive biomarker detection. Experimental studies targeted CA 15-3 and MUC-1 biomarkers in clinical samples, and the biosensor exhibited ease of use and good selectivity. Furthermore, ML algorithms were employed to analyze the electrochemical data and predict biomarker concentrations, enhancing the diagnostic accuracy. The Random Forest algorithm achieved 98% accuracy in tumor presence prediction, while an Artificial Neural Network attained 76% accuracy in CA 15-3-based tumor grade classification. The integration of ML techniques with the GAgNPs-based biosensor offers a promising approach for noninvasive, accurate, and early detection of canine mammary tumors, potentially revolutionizing veterinary diagnostics. This multilayered strategy, combining eco-friendly nanomaterials, electrochemical sensing, and ML algorithms, holds significant potential for advancing both biomedical research and clinical practice in the field of canine mammary tumor diagnostics.

Dynamically controllable hot spots in DNA-derived hydrogel scaffold SERS substrate for exosome recognition using DNA self-assembly amplification

In the context of surface-enhanced Raman scattering (SERS) applications, an effective active substrate is supposed to exhibit a high enhancement factor, long-term stability, and excellent repeatability, as well as allow target molecules to enter the hot spot area with adequate quantity and affinity. The electromagnetic field in hot spots can be drastically amplified and results in an extraordinary large signal enhancement. However, uncontrolled formation of hot spots has hampered the realization of this intention. Here, we reported an innovative SERS active substrate, named as DNA-derived dynamic hydrogel scaffold (DDHS), which is endowed with the robust electromagnetic enhancement and exceptional target affinity. Based on this integrated microfluidic chip, rationally designed DNA oligonucleotides were introduced to recognize exosome indicator-CD63, which achieved a limit of 2.63 particles μL−1. Taken together, we believed that the proposed strategy would be possible to accelerate SERS applied to trace detection of tumor biomarkers, thus offering a promising route toward screening test and early diagnostic of cancerdiseases.

Multiplexed electrochemical nucleic acid sensor based on visible light-mediated metal-free thiol-yne click reaction for simultaneous detection of different nucleic acid targets

Simultaneous detection of multiple tumor biomarkers with a simple and low-cost assay is crucial for early cancer detection and diagnosis. Herein, we presented a low-cost and simple assay for multiplexed detection of tumor biomarkers using a spatially separated electrodes strategy. The sensor is fabricated based on a metal-free thiol-yne click reaction, which is mediated by visible light, on commercially available indium tin oxide (ITO) electrodes. Four biomarkers, including p53 DNA, Brca2 DNA, K-ras DNA, and MicroRNA-204 RNA, were used as model analytes, and the corresponding oligonucleotide probes were modified on the desired electrode units sequentially with 530 nm irradiation light in the presence of photosensitizer Eosin Y. By this visible light-mediated coupling reaction, oligonucleotide probe densities of up to 9.2 ± 0.7 × 1010 molecules/cm2 were readily obtained on the ITO electrode surface. The proposed multiplexed E-NA sensor could detect four different nucleic acid targets concurrently without crosstalk among adjacent electrodes and was also successfully applied for detecting targets in a 20% fetal calf serum sample. The detection limits for p53 DNA, Brca2 DNA, K-ras DNA, and MicroRNA-204 RNA were 0.72 nM, 0.97 nM, 2.15 nM, and 1.73 nM, respectively. The developed approach not only has a great potential for developing cost-effective biosensors on affordable substrates for nucleic acid target detection, but also be easily extended to detect other targets by modifying the specific oligonucleotide probes anchored on the electrode.

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecular biology technologies developed for the detection of tumor biomarkers. Herein, we summarize the discovery and development of tumor biomarkers, including the history of tumor biomarkers, the conventional and innovative technologies used for biomarker discovery and detection, the classification of tumor biomarkers based on tissue origins, and the application of tumor biomarkers in clinical cancer management. In particular, we highlight the recent advancements in biomarker-based anticancer-targeted therapies which are emerging as breakthroughs and promising cancer therapeutic strategies. We also discuss limitations and challenges that need to be addressed and provide insights and perspectives to turn challenges into opportunities in this field. Collectively, the discovery and application of multiple tumor biomarkers emphasized in this review may provide guidance on improved precision medicine, broaden horizons in future research directions, and expedite the clinical classification of cancer patients according to their molecular biomarkers rather than organs of origin.

A novel split-type photoelectrochemical biosensor based on liposome-induced in situ formation of Bi2S3@BiOI/Ag2S heterojunction for the sensitive detection of CEA

A novel split-type photoelectrochemical (PEC) biosensor was constructed for the sensitive detection of carcinoembryonic antigen (CEA) based on the Ag+-liposome (ALL) signal amplification strategy and Bi2S3@BiOI heterojunction as the substrate material. The split-type sensing mode effectively avoids the complex fixation of biomolecules on the electrode surface and preserves the activity of biomolecules. The sandwich complex was formed between CEA and aptamer-anchored streptavidin-functionalized magnetic beads (SMB-Apt) and ALL-labeled aptamer (ALL-Apt). After the methanol was added, a large amount of Ag+ was released from the liposome. The released Ag+ was transferred to the Bi2S3@BiOI modified electrode surface for incubation and then soaked in Na2S solution to form a narrow band gap photosensitive material Ag2S on the electrode surface. Bi2S3@BiOI/Ag2S ternary heterojunction in situ was formed due to the band gap matching relationship between Ag2S and the Bi2S3@BiOI heterojunction, which effectively expanded the light absorption range and enhanced the photocurrent signal. Under the optimal experimental conditions, the constructed PEC sensing platform exhibited good analytical performance for CEA with a linear range of 0.005 ∼ 50 ng mL−1 and a detection limit of 1.21 pg mL−1. Additionally, the PEC sensor had good selectivity, reproducibility, and stability, which provided a new research idea for the detection of clinical tumor biomarkers.

New Perspectives on the Role of Liquid Biopsy in Bladder Cancer: Applicability to Precision Medicine.

Bladder cancer (BC) is one of the most common tumors in the world. Cystoscopy and tissue biopsy are the standard methods in screening and early diagnosis of suspicious bladder lesions. However, they are invasive procedures that may cause pain and infectious complications. Considering the limitations of both procedures, and the recurrence and resistance to BC treatment, it is necessary to develop a new non-invasive methodology for early diagnosis and multiple evaluations in patients under follow-up for bladder cancer. In recent years, liquid biopsy has proven to be a very useful diagnostic tool for the detection of tumor biomarkers. This non-invasive technique makes it possible to analyze single tumor components released into the peripheral circulation and to monitor tumor progression. Numerous biomarkers are being studied and interesting clinical applications for these in BC are being presented, with promising results in early diagnosis, detection of microscopic disease, and prediction of recurrence and response to treatment.

Sensitive Electrochemical Detection of Carcinoembryonic Antigen Based on Biofunctionalized Nanochannel Modified Carbonaceous Electrode.

The convenient construction of carbon-based electrochemical immunosensors with high performance is highly desirable for the efficient detection of tumor biomarkers. In this work, an electrochemical immunosensor was fabricated by integrating a biofunctionalized mesoporous silica nanochannel film with a carbon-based electrode, which can enable the sensitive determination of carcinoembryonic antigen (CEA) in serum. The commonly used carbonaceous electrode, glassy carbon electrode (GCE), was employed as the supporting electrode and was pre-treated through electrochemical polarization to achieve the stable binding of a vertically ordered mesoporous silica film with amino groups (NH2-VMSF) without the use of any adhesive layer. To fabricate the immunorecognition interface, antibodies were covalently immobilized after the amino groups on the outer surface of NH2-VMSF was derivatized to aldehyde groups. The presence of amino sites within the high-density nanochannels of NH2-VMSF can facilitate the migration of negatively charged redox probes (Fe(CN)63-/4-) to the supporting electrode through electrostatic adsorption, leading to the generation of electrochemical signals. In the presence of CEA, the formation of immunocomplexes on the recognitive interface can reduce the electrochemical signal of Fe(CN)63-/4- on the supporting electrode. Based on this principle, the sensitive electrochemical detection of CEA was achieved. CEA can be determined to range from 0.01 ng mL-1 to 100 ng mL-1 with a limit of detection of 6.3 pg mL-1. The fabricated immunosensor exhibited high selectivity, and the detection of CEA in fetal bovine serum was achieved.

Smartphone-assisted self-powered dual-mode biosensor designed on binary 3D DNA Walkers mediated CRISPR/Cas12a system

Malignant tumors are significant diseases that pose a threat to human life and health. The advancement of highly sensitive and specific methods is of excellent significance. This study proposes a novel detection platform that employs a smartphone-assisted self-powered sensing system with binary 3D DNA Walkers mediated CRISPR/Cas12a system and ultra-thin 2D graphdiyne for ultrasensitive dual-mode detection of breast cancer biomarker microRNA-let-7a. The binary 3D DNA Walkers possess high efficiency in movement and multifunctional characteristics. When combined with the CRISPR/Cas12a system, they can retain the advantages of 3D DNA Walker while releasing a large of trigger strands complementary to CRISPR RNA, thereby greatly enhancing the sensitivity of the sensor. In addition, capacitors are also integrated into the sensing system to further amplify the detection signal, resulting in a 20.7-fold increase in sensitivity of the method. Additionally, the adoption of an electrochemical/colorimetric dual-mode detection strategy significantly enhances the accuracy of the new approach. The newly developed detection method exhibits a linear range of 0.0001–10000 pM with a detection limit of 8.11 aM (S/N = 3). This work offers a reliable portable sensor for sensitive and accurate detection of tumor biomarkers, enabling remote disease sensing and on-site monitoring applications.

A Novel Label-Free Electrochemical Immunosensor for the Detection of Thyroid Transcription Factor 1 Using Ribbon-like Tungsten Disulfide-Reduced Graphene Oxide Nanohybrids and Gold Nanoparticles.

Thyroid transcription factor 1 (TTF1) is an important cancer-related biomarker for clinical diagnosis, especially for carcinomas of lung and thyroid origin. Herein, a novel label-free electrochemical immunosensor was prepared for TTF1 detection based on nanohybrids of ribbon-like tungsten disulfide-reduced graphene oxide (WS2-rGO) and gold nanoparticles (AuNPs). The proposed immunosensor employed H2O2 as the electrochemical probe because of the excellent peroxidase-like activity of ribbon-like WS2-rGO. The introduction of AuNPs not only enhanced the electrocatalytic activity of the immunosensor, but also provided immobilization sites for binding TTF1 antibodies. The electrochemical signals can be greatly amplified due to their excellent electrochemical performance, which realized the sensitive determination of TTF1 with a wide linear range of 0.025-50 ng mL-1 and a lower detection limit of 0.016 ng mL-1 (S/N = 3). Moreover, the immunosensor exhibited high selectivity, good reproducibility, and robust stability, as well as the ability to detect TTF1 in human serum with satisfactory results. These observed properties of the immunosensor enhance its potential practicability in clinical applications. This method can also be used for the detection of other tumor biomarkers by using the corresponding antigen-antibody complex.

Split-type photoelectrochemical immunoassay for sensitive quantification of carcinoembryonic antigen based on target-induced in situ formation of Z-type heterojunction.

Carcinoembryonic antigen (CEA), a vital biomarker, plays a significant role in the early diagnosis and prognostic estimation of malignant tumors. In this study, a split-type photoelectrochemical immunoassay for the sensitive quantification of CEA has been successfully developed based on the target-induced in situ formation of a Z-type heterojunction. First, gold nanoparticle-decorated ZnIn2S4 (AuNPs/ZnIn2S4) composites were synthesized and used for the fabrication of photoelectrodes. Then, the detection antibody labeled with Ag nanoparticles was formed and applied for the biorecognition of CEA and subsequent liberation of Ag+ ions to induce the in situ formation of Ag2S/AuNPs/ZnIn2S4, a Z-type heterojunction, on the photoelectrode. The Z-type Ag2S/AuNPs/ZnIn2S4 heterojunction with effectively promoted separation of photogenerated charge carriers could lead to a markedly enhanced photocurrent response and highly sensitive quantification of CEA. Moreover, the three-dimensional spatial structure of ZnIn2S4 provides abundant active sites for the reaction and exhibits non-enzymatic properties, which are conducive to the further improvement of the analytical performance of CEA. The developed split-type photoelectrochemical immunoassay with good sensitivity, satisfactory selectivity, reliable stability, wide dynamic linear range (0.01-20 ng mL-1), and low detection limit (7.3 pg mL-1) offers valuable insights into the development of novel PEC biosensing models for the detection of tumor biomarkers and holds potential application value in the field of disease diagnosis.

Metabolomics Analysis and Diagnosis of Lung Cancer: Insights from Diverse Sample Types.

Lung cancer is a highly fatal disease that poses a significant global health burden. The absence of characteristic clinical symptoms frequently results in the diagnosis of most patients at advanced stages of lung cancer. Although low-dose computed tomography (LDCT) screening has become increasingly prevalent in clinical practice, its high rate of false positives continues to present a significant challenge. In addition to LDCT screening, tumor biomarker detection represents a critical approach for early diagnosis of lung cancer; unfortunately, no tumor marker with optimal sensitivity and specificity is currently available. Metabolomics has recently emerged as a promising field for developing novel tumor biomarkers. In this paper, we introduce metabolic pathways, instrument platforms, and a wide variety of sample types for lung cancer metabolomics. Specifically, we explore the strengths, limitations, and distinguishing features of various sample types employed in lung cancer metabolomics research. Additionally, we present the latest advances in lung cancer metabolomics research that utilize diverse sample types. We summarize and enumerate research studies that have investigated lung cancer metabolomics using different metabolomic sample types. Finally, we provide a perspective on the future of metabolomics research in lung cancer. Our discussion of the potential of metabolomics in developing new tumor biomarkers may inspire further study and innovation in this dynamic field.

Enhanced NIR-II Fluorescent Lateral Flow Biosensing Platform Based on Supramolecular Host-Guest Self-Assembly for Point-of-Care Testing of Tumor Biomarkers.

Point-of-care detection of tumor biomarkers with high sensitivity remains an enormous challenge in the early diagnosis and mass screening of cancer. Fluorescent lateral flow immunoassay (LFA) is an attractive platform for point-of-care testing due to its inherent advantages. Particularly, a fluorescent probe is crucial to improving the analytical performance of the LFA platform. Herein, we developed an enhanced second near-infrared (NIR-II) LFA (ENIR-II LFA) platform based on supramolecular host-guest self-assembly for detection of the prostate-specific antigen (PSA) as a model analyte. In this platform, depending on the effective supramolecular surface modification strategy, cucurbit[7]uril (CB[7])-covered rare-earth nanoparticles (RENPs) emitting in the NIR-II (1000-1700 nm) window were prepared and employed as an efficient fluorescent probe (RENPs-CB[7]). Benefiting from its superior optical properties, such as low autofluorescence, excellent photostability, enhanced fluorescence intensity, and increased antibody-conjugation efficiency, the ENIR-II LFA platform displayed a wide linear detection range from 0.65 to 120 ng mL-1, and the limit of detection was down to 0.22 ng mL-1 for PSA, which was 18.2 times lower than the clinical cutoff value. Moreover, the testing time was also shortened to 6 min. Compared with the commercial visible fluorescence LFA kit (VIS LFA) and the previously reported NIR-II LFA based on a RENPs-PAA probe, this ENIR-II LFA demonstrated more competitive advantages in analytical sensitivity, detection range, testing time, and production cost. Overall, the ENIR-II LFA platform offers great potential for the highly sensitive, rapid, and convenient detection of tumor biomarkers and is expected to serve as a useful technique in the general population screening of the high-incidence cancer region.

Bimetallic Nanozyme: A Credible Tag for In Situ-Catalyzed Reporter Deposition in the Lateral Flow Immunoassay for Ultrasensitive Cancer Diagnosis.

The lateral flow immunoassay (LFIA) is a sought-after point-of-care testing platform, yet the insufficient sensitivity of the LFIA limits its application in the detection of tumor biomarkers. Here, a colorimetric signal amplification method, bimetallic nanozyme-mediated in situ-catalyzed reporter deposition (BN-ISCRD), was designed for ultrasensitive cancer diagnosis. The bimetallic nanozyme used, palladium@iridium core-shell nanoparticles (Pd@Ir NPs), had ultrahigh enzyme-like activity, which was further explained by the electron transfer of Pd@Ir NPs and the change in the Gibbs free energy during catalysis through density functional theory calculations. With gastric cancer biomarkers pepsinogen I and pepsinogen II as model targets, this assay could achieve a cutoff value of 10 pg/mL, which was 200-fold lower than that without signal enhancement. The assay was applied to correctly identify 8 positive and 28 negative clinical samples. Overall, this BN-ISCRD-based LFIA showed great merits and potential in the application of ultrasensitive disease diagnosis.

Label-Free Homogeneous Electrochemical Aptasensor Based on Size Exclusion/Charge-Selective Permeability of Nanochannel Arrays and 2D Nanorecognitive Probe for Sensitive Detection of Alpha-Fetoprotein.

The labeling-free and immobilization-free homogeneous aptamer sensor offers advantages including simple operation, low cost, and high sensitivity, demonstrating great potential in rapid detection of tumor biomarkers in biological samples. In this work, a labeling-free and immobilization-free homogeneous aptamer sensor was conveniently fabricated by combining size exclusion and charge-selective penetration of a nanochannel-modified electrode and two-dimensional (2D) nanorecognition probe which can realize selective and highly sensitive detection of alpha-fetoprotein (AFP) in serum. Vertically ordered mesoporous silica film (VMSF) with ultra-small, uniform, and vertically aligned nanochannels was easily grown on the simple, low-cost, and disposable indium tin oxide (ITO) electrode. Through π-π interaction and electrostatic force, the AFP aptamer (Apt) and electrochemical probe, tris(bipyridine)ruthenium(II) (Ru(bpy)32+), were coloaded onto graphene oxide (GO) through simple incubation, forming a 2D nanoscale recognition probe (Ru(bpy)32+/Apt@GO). Owing to the size exclusion effect of VMSF towards the 2D nanoscale probe, the electrochemical signal of Ru(bpy)32+/Apt@GO could not be detected. In the presence of AFP, the specific binding of AFP to the aptamer causes the dissociation of the aptamer and Ru(bpy)32+ from GO, resulting in their presence in the solution. The efficient electrostatic enrichment towards Ru(bpy)32+ by negatively charged VMSF allows for high electrochemical signals of free Ru(bpy)32+ in the solution. Linear determination of AFP ranged from 1 pg/mL to 1000 ng/mL and could be obtained with a low limit of detection (LOD, 0.8 pg/mL). The high specificity of the adapter endowed the constructed sensor with high selectivity. The fabricated probe can be applied in direct determination of AFP in serum.

Effects of anthracycline chemotherapy and Kuan-Sin-Yin on the spectral indices of arterial pulse waveforms in breast cancer patients.

The vascular structure and function are potentially useful biomarkers for tumor detection. Treatment with chemotherapeutic agents may impair vascular function and increase the risk of cardiovascular disease. This study aimed to use noninvasive pulse waveform measurements to identify differences in the frequency-domain indices of the pulse waveform in breast-cancer patients following anthracycline chemotherapy between with (Group KSY) and without (Group NKSY) receiving Kuan-Sin-Yin (KSY) treatment.Radial blood pressure waveform (BPW) signals were measured noninvasively for 3 minutes in 31 patients, and the FACT-G, BFI-T, and EORTC QLQ-C30 questionnaires were administered. The following pulse indices were calculated for 10 harmonics: the amplitude proportion and its coefficient of variation, and the phase angle and its standard deviation.The changes in spectral BPW indices were more prominent in Group NKSY than in Group KSY, especially for the decreases in BPW variability indices. Scores on the FACT-G, BFI-T, and EORTC QLQ-C30 questionnaires suggested that the quality of life following chemotherapy was better in Group KSY.The identified decreases in pulse variability indices could be related to the greater impairment of regulatory activities in Group NKSY. The present findings may be meaningful in developing techniques with advantages such as being noninvasive and time-saving to evaluate the blood supply and physiological conditions following chemotherapy or other treatment strategies in cancer patients.

Immunosensor with Enhanced Electrochemiluminescence Signal Using Platinum Nanoparticles Confined within Nanochannels for Highly Sensitive Detection of Carcinoembryonic Antigen.

Rapid, highly sensitive, and accurate detection of tumor biomarkers in serum is of great significance in cancer screening, early diagnosis, and postoperative monitoring. In this study, an electrochemiluminescence (ECL) immunosensing platform was constructed by enhancing the ECL signal through in situ growth of platinum nanoparticles (PtNPs) in a nanochannel array, which can achieve highly sensitive detection of the tumor marker carcinoembryonic antigen (CEA). An inexpensive and readily available indium tin oxide (ITO) glass electrode was used as the supporting electrode, and a layer of amino-functionalized vertically ordered mesoporous silica film (NH2-VMSF) was grown on its surface using an electrochemically assisted self-assembly method (EASA). The amino groups within the nanochannels served as anchoring sites for the one-step electrodeposition of PtNPs, taking advantage of the confinement effect of the ultrasmall nanochannels. After the amino groups on the outer surface of NH2-VMSF were derivatized with aldehyde groups, specific recognition antibodies were covalently immobilized followed by blocking nonspecific binding sites to create an immunorecognition interface. The PtNPs, acting as nanocatalysts, catalyzed the generation of reactive oxygen species (ROS) with hydrogen peroxide (H2O2), significantly enhancing the ECL signal of the luminol. The ECL signal exhibited high stability during continuous electrochemical scanning. When the CEA specifically bound to the immunorecognition interface, the resulting immune complexes restricted the diffusion of the ECL emitters and co-reactants towards the electrode, leading to a reduction in the ECL signal. Based on this immune recognition-induced signal-gating effect, the immunosensor enabled ECL detection of CEA with a linear range of 0.1 pg mL-1 to 1000 ng mL-1 with a low limit of detection (LOD, 0.03 pg mL-1). The constructed immunosensor demonstrated excellent selectivity and can achieve CEA detection in serum.

A highly sensitive electrochemical magneto-genosensing assay for the specific detection of a single nucleotide variation in the KRAS oncogene in human plasma

Liquid biopsy is a non-invasive and efficient technique for the detection of tumor biomarkers in biological fluids, which currently represents a new frontier in theranostics and precision medicine. Among mutations of the KRAS oncogene, p.G12D single nucleotide variation in the KRAS gene plays a central role in the early diagnosis and therapeutic treatment of colorectal cancer. In this context, we developed a highly sensitive magneto-genosensing assay based on PNA capture probes immobilized on magnetic microbeads. To detect the mutation of the KRAS oncogene, two capture probe sequences recognizing wild-type and p.G12D tumor DNA were used in association with a DNA signaling probe allowing for electrochemical detection using an enzyme conjugate. The assay conditions were optimized using a 32 full-factorial design, obtaining an outstanding specificity, evidenced by a remarkably lower (>95%) signal of the singly-mismatched- compared to that of fully-complementary-DNA. Ultra-high sensitivity was achieved in 10-fold diluted human plasma reaching detection limits of 818 fM for the p.G12D and 1.8 pM for the wild-type targets. The genosensing assay was tested on genomic tumor DNA samples provided by IRCCS-Regina Elena National Cancer Institute and finally integrated into a smart portable multichannel potentiostat capable of performing up to four simultaneous acquisitions. The developed magneto-genosensing assay demonstrated portability, simplicity, and high sensitivity, showing good potential as theranostic tool for personalized medicine in oncology.

Deep learning-based detection and identification of brain tumor biomarkers in quantitative MR-images

The infiltrative nature of malignant gliomas results in active tumor spreading into the peritumoral edema, which is not visible in conventional magnetic resonance imaging (cMRI) even after contrast injection. MR relaxometry (qMRI) measures relaxation rates dependent on tissue properties and can offer additional contrast mechanisms to highlight the non-enhancing infiltrative tumor. To investigate if qMRI data provides additional information compared to cMRI sequences when considering deep learning-based brain tumor detection and segmentation, preoperative conventional (T1w per- and post-contrast, T2w and FLAIR) and quantitative (pre- and post-contrast R1, R2 and proton density) MR data was obtained from 23 patients with typical radiological findings suggestive of a high-grade glioma. 2D deep learning models were trained on transversal slices (n = 528) for tumor detection and segmentation using either cMRI or qMRI. Moreover, trends in quantitative R1 and R2 rates of regions identified as relevant for tumor detection by model explainability methods were qualitatively analyzed. Tumor detection and segmentation performance for models trained with a combination of qMRI pre- and post-contrast was the highest (detection Matthews correlation coefficient (MCC) = 0.72, segmentation dice similarity coefficient (DSC) = 0.90), however, the difference compared to cMRI was not statistically significant. Overall analysis of the relevant regions identified using model explainability showed no differences between models trained on cMRI or qMRI. When looking at the individual cases, relaxation rates of brain regions outside the annotation and identified as relevant for tumor detection exhibited changes after contrast injection similar to region inside the annotation in the majority of cases. In conclusion, models trained on qMRI data obtained similar detection and segmentation performance to those trained on cMRI data, with the advantage of quantitatively measuring brain tissue properties within a similar scan time. When considering individual patients, the analysis of relaxation rates of regions identified by model explainability suggests the presence of infiltrative tumor outside the cMRI-based tumor annotation.

Applying thermodynamics as an applicable approach to cancer diagnosis, evaluation, and therapy: A review

Numerous researchers and scientists are trying to develop novel methods and technologies to treat cancers more efficiently and quickly. One of the most important steps to treat cancers efficiently is to diagnose them at their early stage and for this purpose, diverse selective and sensitive biosensors have been developed which operate based on the affinity of electrode-analyte interactions that can be interpreted and modified by thermodynamics to fabricate the best method with the highest sensitivity for the early detection of cancers. Another crucial step for effective cancer therapy is to determine the cancer stage which can be done by evaluating entropy generation or by employing nanoparticles with thermodynamic-based mechanisms for tumor imaging, biomarker detection, and tumor detection. As the last step, thermodynamics can be applied effectively as an applicable approach for treating diverse cancers, either by employing a photothermal-thermodynamic combination technique or thermosensitive hydrogel-based drug delivery systems. This study, by providing recent achievements and discussing the challenges of the thermodynamic applications in cancer diagnosis, tumor progression evaluation, and cancer therapy is dedicated to be an inspirational study for further investigation, optimization, and progression of the thermodynamic applications in biomedical purposes. Moreover, researchers can implement further works with higher efficacy in this field by understanding thermodynamic applications and backgrounds.