Sensitive Detection Research Articles

Abstract PO5-05-13: Clinical utility of whole body low dose computed tomography for detecting bone metastasis in breast cancer patients: A cross sectional study

Abstract Clinical utility of Whole Body Low Dose CT scan for detecting bone metastasis in Breast cancer patients: A cross sectional study Background: Skeletal scintigraphy (Bone scan) is the imaging of choice to detect bone metastasis in locally advanced and metastatic breast cancer patients. Nuclear medicine facilities are however limited in their availability. As an alternative diagnostic modality to bone scan, we studied the diagnostic capability of Whole-Body Low Dose CT (WBLDCT) scan for detection of bone metastasis in these patients. Materials and Method: This cross-sectional study was conducted from November 2021 to May 2023 at a tertiary healthcare center in India with an aim to study the clinical applicability of whole-body low dose computed tomography scan for detecting bone metastasis in patients with breast cancer. Breast cancer patients with primary tumor measuring 5cm or more, pathologically proven axillary lymph node metastasis, Stage III/IV disease, symptoms attributable to metastasis and suspected disease recurrence were included. All patients underwent WBLDCT and Bone scan within a period of about 2 weeks. WBLDCT was done during the same time as conventional dose CT scan was being done as part of metastatic workup. WBLDCT acquisition protocol was set in CT scan machine by modulating the technical parameters like Care dose 4D-automated, Care kV semi, rotation time & noise index. The image analysis was performed by Radiologist and Nuclear medicine experts in a blinded fashion. Data was recorded in MS Excel sheet. Sensitivity, specificity, positive and negative predicative value, and concordance rates were calculated using SPSS software ver 25.0. Agreement amongst WBLDCT and Bone scan was calculated using Inter-rater agreement. p value < 0.05 was taken as significant. Results: 110 patients were enrolled in this study. The mean age of participants was 48.5 years and three fourth had stage III disease at presentation. Estrogen receptor positive disease was seen in 43.64% participants while 30% were triple negative. Her2neu positive disease was seen in 27.27% patients. Bone scan couldn’t be done in 03 patients who deferred treatment (these had no bone metastasis on WBLDCT). Both bone scan and WBLDCT detected bone metastasis in 19 patients. Bone scan picked up additional metastasis in three patients which were missed on WBLDCT. WBLDCT detected bone metastasis additionally in three patients which were not detected on Bone scan. Multiple lesions were most seen in vertebrae in 38.5% and 28.6% on bone scan and WBLDCT respectively. The sensitivity and specificity of WBLDCT for detection of bone metastasis was 86.36% and 96.47% respectively. The concordance rate between Bone scan and WBLDCT scan was 94.39% with an Inter-rater Kappa(k) quotient for agreement of 0.828 (p< 0.0001). Conclusion: WBLDCT scan has comparable diagnostic capability to skeletal scintigraphy in detecting bone metastasis in breast cancer and may be a useful alternative specially in resource limited settings. Table 1: Sensitivity, specificity, positive predictive value and negative predictive value of WBLDCT for detection of metastasis Variables Values Sensitivity (95% CI) 86.36% Specificity (95% CI) 96.47% AUC (95% CI) 0.91 Positive Predictive Value (95% CI) 86.36% Negative Predictive Value (95% CI) 96.47% Diagnostic accuracy 94.39% Inter-rater agreement (kappa) 0.828 Citation Format: Lipton Mitra, Suhani Suhani, Ankur Goyal, Rakesh Kumar, Mohit Joshi, Hemanga Bhattacharjee, Haresh KP, Raju Sharma, Rajinder Parshad. Clinical utility of whole body low dose computed tomography for detecting bone metastasis in breast cancer patients: A cross sectional study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-13.

Enhancement of Upconversion Luminescence through Three-Dimensional Design of Plasma Ti3O5-Coupled Structural Domain-Limiting Effects.

Upconversion luminescence plays a crucial role in various technological applications, and among the various valence states of lanthanide elements, Ln3+ has the highest stability. The 4f orbitals of these elements are in a fully empty, semifull, or full state. This special 4f electron configuration allows them to exhibit rich discrete energy levels. However, the 4f-4f transition of Ln3+ rare earth ions itself is prohibited, resulting in a lower luminescence efficiency. This limitation greatly hinders the practical application of upconversion luminescence. In this study, we report nanostructured luminescence-enhanced substrate platforms with both semiconductive local surface plasmons and spatially confined domain effects on a single defect semiconductor substrate. By coupling NaYF4:Yb-Er nanoparticle emitters to the surface of Ti3O5 NC-arrays plasmonic nanostructures, an ultrabright luminescence with a 32-fold increase in green emission and a 40-fold increase in red emission was achieved. Furthermore, the fluorescence resonance energy transfer characteristics observed in the R6G/NaYF4/Ti3O5 NC-array composite film enable accurate detection of fluorescent molecules. The results provide an innovative and intelligent approach to enhance the upconversion luminescence intensity of rare-doped nanoparticles and develop highly sensitive molecular detection systems based on the above luminescence enhancement.

Hydrogel-Coated SERS Microneedles for Drug Monitoring in Dermal Interstitial Fluid.

In vivo drug monitoring is crucial for evaluating the effectiveness and safety of drug treatment. Blood sampling and analysis is the current gold standard but needs professional skills and cannot meet the requirements of point-of-care testing. Dermal interstitial fluid (ISF) showed great potential to replace blood for in vivo drug monitoring; however, the detection was challenging, and the drug distribution behavior in ISF was still unclear until now. In this study, we proposed surface-enhanced Raman spectroscopy (SERS) microneedles (MNs) for the painless and real-time analysis of drugs in ISF after intravenous injection. Using methylene blue (MB) and mitoxantrone (MTO) as model drugs, the innovative core-satellite structured Au@Ag SERS substrate, hydrogel coating over the MNs, rendered sensitive and quantitative drug detection in ISF of mice within 10 min. Based on this technique, the pharmacokinetics of the two drugs in ISF was investigated and compared with those in blood, where the drugs were analyzed via liquid chromatography-mass spectrometry. It was found that the MB concentration in ISF and blood was comparable, whereas the concentration of MTO in ISF was 2-3 orders of magnitude lower than in blood. This work proposed an efficient tool for ISF drug monitoring. More importantly, it experimentally proved that the penetration ratio of blood to ISF was drug-dependent, providing insightful information into the potential of ISF as a blood alternative for in vivo drug detection.

Prussian Blue Analogues-Derived Molecularly Imprinted Nanozyme Array for Septicemia Detection.

Septicemia, a severe bacterial infection, poses significant risks to human health. Early detection of septicemia by tracking specific biomarkers is crucial for a timely intervention. Herein, we developed a molecularly imprinted (MI) TiO2-Fe-CeO2 nanozyme array derived from Ce[Fe(CN)6] Prussian blue analogues (PBA), specifically targeting valine, leucine, and isoleucine, as potential indicators of septicemia. The synthesized nanozyme arrays were thoroughly characterized using various analytical techniques, including Fourier transform infrared spectroscopy, X-ray diffraction, field-emission scanning electron microscope, and energy-dispersive X-ray. The results confirmed their desirable physical and chemical properties, indicating their suitability for the oxidation of 3,3',5,5'-tetramethylbenzidine serving as a colorimetric probe in the presence of a persulfate oxidizing agent, further highlighting the potential of these arrays for sensitive and accurate detection applications. The MITiO2 shell selectively captures valine, leucine, and isoleucine, partially blocking the cavities for substrate access and thereby hindering the catalyzed TMB chromogenic reaction. The nanozyme array demonstrated excellent performance with linear detection ranges of 5 μM to 1 mM, 10-450 μM, and 10-450 μM for valine, leucine, and isoleucine, respectively. Notably, the corresponding limit of detection values were 0.69, 1.46, and 2.76 μM, respectively. The colorimetric assay exhibited outstanding selectivity, reproducibility, and performance in the detection of analytes in blood samples, including C-reactive protein at a concentration of 61 mg/L, procalcitonin at 870 ng/dL, and the presence of Pseudomonas aeruginosa bacteria. The utilization of Ce[Fe(CN)6]-derived MITiO2-Fe-CeO2 nanozyme arrays holds considerable potential in the field of septicemia detection. This approach offers a sensitive and specific method for early diagnosis and intervention, thereby contributing to improved patient outcomes.

Abstract PO2-13-08: Cell-free orphan noncoding RNAs and AI enable early detection of invasive breast cancer and ductal carcinoma in-situ

Abstract Background Earlier detection of breast cancer through mammography screening has reduced disease-specific mortality; however, confounding issues such as technical challenges, breast density, and tumor size can result in false negatives and ultimately later stage diagnosis. Next generation liquid biopsy has the potential to complement mammography and enable earlier detection for more women. We have previously demonstrated high sensitivity and specificity for early detection of invasive breast cancer (IBC) by utilizing a novel category of cancer-associated small RNAs, termed orphan noncoding RNAs (oncRNAs), through a liquid biopsy platform. Here, we further improve the ability to detect breast cancer in a larger, multi-source cohort through an AI-driven approach and demonstrate potential for detection of ductal carcinoma in-situ (DCIS). Methods We utilized The Cancer Genome Atlas (TCGA) small RNA-seq database to discover a library of 20,538 oncRNAs, through a female-specific analysis, that were significantly enriched among 1,103 breast tumors compared to 349 normal tissue samples spanning multiple tissue sites. The diagnostic performance of these oncRNAs were assessed in an independent cohort of archived serum samples from 663 female individuals, sourced from Indivumed (Hamburg, Germany), Proteogenex (Inglewood, CA), and MT Group (Los Angeles, CA), including 279 breast cancer patients of various stages (221 IBC and 58 DCIS; mean age: 57.0 ± 13.8 years; ever-smoker: 25.8%) and 304 age-matched controls (mean age: 58.5 ± 13.9 years; ever-smoker: 23.4%) without breast cancer. All samples were collected between 2010–2022 at time of diagnosis for breast cancer patients. We sequenced the small RNA content of these samples at an average depth of 25.28 ± 9.37 million 50-bp single-end reads. We detected 18,025 (87.8%) unique breast cancer-specific oncRNA species within at least one sample from the study cohort. We then trained a generative AI model using 5-fold cross-validation to predict cancer status for all samples. Results Our oncRNA-based model achieved an overall AUC of 0.95 (95% CI, 0.93–0.97) for prediction of IBC versus cancer-free controls with a sensitivity of 0.87 (0.82–0.91) at 90% specificity. We observed high sensitivities, also at 90% specificity, across all tumor stages and tumor sizes (Table 1). Sensitivities for the earliest stage and smallest tumor size were 0.87 (0.78–0.93) and 0.81 (0.61–0.93) for Stage I (n=83) and T1a–b ( >1mm to ≤10mm; n=26), respectively. Additionally, in a small single-source cohort, we also saw high model accuracy and sensitivity for DCIS, which we aim to confirm in additional cohorts. While our overall cancer cohort primarily consisted of individuals with luminal breast cancer, our model had high sensitivities across all breast cancer subtypes at 0.90 (0.84–0.94), 0.73 (0.59–0.85), and 0.86 (0.42–1.0) for luminal (n=181), HER2 positive (n=49), and triple negative (n=7), respectively. Conclusions We further demonstrate the potential utility of oncRNAs as a blood-based biomarker using an AI algorithm for sensitive and accurate early detection of breast cancer in a large cohort. Additionally, we have shown that this oncRNA-based assay performs well in detecting small, early-stage invasive breast tumors, with potential to detect precursors of breast cancer. Table 1: Model sensitivity in breast cancer by tumor stage and size For each tumor stage and size, as defined by the AJCC 7th Edition breast cancer staging system, sensitivity and 95% Pearson-Clopper confidence intervals (CI) are reported at 90% specificity for the number of samples (N). Citation Format: Noura Tbeileh, Taylor Cavazos, Mehran Karimzadeh, Jeffrey Wang, Alice Huang, Dung Ngoc Lam, Seda Kilinc, Jieyang Wang, Xuan Zhao, Andy Pohl, Helen Li, Lisa Fish, Kimberly Chau, Marra Francis, Lee Schwartzberg, Patrick Arensdorf, Hani Goodarzi, Fereydoun Hormozdiari, Babak Alipanahi. Cell-free orphan noncoding RNAs and AI enable early detection of invasive breast cancer and ductal carcinoma in-situ [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-13-08.

Abstract PS06-06: Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer

Abstract Background: The detection of ctDNA in patients with early-stage breast cancer after completion of adjuvant therapy is associated with a high risk of recurrence. Current clinical guidelines do not recommend routine screening for metastatic disease unless there are clinical signs and symptoms in patients who completed adjuvant therapy. However, ctDNA may serve as an early biomarker of recurrence which may allow effective identification of patients with asymptomatic distant metastases or molecular relapse only, who could benefit from early treatment intervention. Herein, we utilized a tissue-free, multiomic assay for the sensitive and specific detection of MRD in patients with early-stage breast cancer. Methods: Plasma samples were collected from patients with stage I-III breast cancer who were enrolled in the SUCCESS-A phase 3 clinical trial (NCT02181101) between 2006 and 2007. All patients received adjuvant chemotherapy +/- endocrine therapy and/or anti-HER2 therapy. Samples were collected approximately two years after completion of adjuvant chemotherapy, and plasma samples selected for analysis were from patients without evidence of disease recurrence prior to sample collection. Presence of MRD was assessed using Guardant Reveal powered by Infinity, which evaluates the epigenomic signals associated with cancer versus normal DNA for the detection of ctDNA. Samples with the presence of ctDNA are characterized for somatic alterations with common sources of interference such as clonal hematopoiesis excluded. An analytically validated bioinformatics pipeline was used for the detection of breast cancer ctDNA. Samples were analyzed blinded to the clinical data. Median survival times were estimated using the Kaplan-Meier method and hazard ratios were calculated based on univariable cox regression models. Results: A total of 311 plasma samples from 311 patients were evaluable. ctDNA was detected in 34% (13/38) of patients who subsequently developed distant recurrence and in none (0/7) of the patients who had local or contralateral breast cancer recurrence. ctDNA was detected in 60% (9/15) of samples that were collected within one year before recurrence. In the ctDNA detected samples from patients who had disease recurrence, the median time from sample collection to recurrence was 7.9 months (range, 1.4-28.6 months). ctDNA was detected in 6 patients who did not have a documented disease recurrence, resulting in a specificity of 97.7% (260/266). In the overall cohort, ctDNA detection was prognostic for recurrence-free survival (RFS; HR 11.0, 95% CI 2.28-53.6; p< 0.0001), distant recurrence-free survival (D-RFS; HR 13.7, 95% CI 2.52-74.9; p< 0.0001), and overall survival (OS; HR 17.4, 95% CI 1.33-227; p< 0.0001). Conclusion: Detection of ctDNA after adjuvant chemotherapy was highly prognostic and demonstrated high specificity in an early-stage breast cancer cohort. Larger, prospective studies are needed to confirm the prognostic value of ctDNA in the post-treatment setting and assess the clinical utility of MRD detection in this population. Citation Format: Wolfgang Janni, Thomas Friedl, Brigitte Rack, Peter A. Fasching, Andreas Hartkopf, Hans Tesch, Ralf Lorenz, Georg Heinrich, Jens-Uwe Blohmer, Tanja Fehm, Volkmar Müller, Andreas Schneeweiss, Matthias Beckmann, Matthias Ruebner, Nadia Harbeck, Klaus Pantel, Derek Dustin, Mingyang Cai. Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS06-06.

An Unconventional Immunosensor for Biomolecule Detection via Nonspecific Gold Nanoparticle-Antibody Interactions.

Immunogold, that is, gold nanoparticles (AuNPs) conjugated with biomolecules such as antibodies and peptides, have been widely used to construct sandwiched immunosensors for biodetection. Two main challenges in these immunoassays are difficulties in finding and validating a suitable antibody, and the nonspecific interaction between the substrate and immunogold, which lowers the detection sensitivity and even causes false results. To avoid these issues, we took advantage of the nonspecific interaction between AuNPs and capture antibodies and proposed a new sensing mechanism. That is, after the capture of analyte targets by the capture antibodies on the substrate, AuNPs of certain chemical functionality would preferably bind to the free capture antibodies. Consequently, the amount of deposited AuNPs will inversely depend on the concentration of the analytes. As a proof-of-concept, we designed a mass-based sensor where anti-IgG antibodies were coated on a quartz crystal microbalance substrate. After IgG was introduced, tannic acid-capped AuNPs were applied to bind with the free anti-IgG antibody molecules. A frequency change (Δf) of the quartz substrate was induced by the increased mass loading. To further amplify the loading mass, an Ag enhancer solution was added, and Ag growth was catalyzed by the bound AuNPs. The Δf response showed a concentration-dependent decrease when increasing IgG concentration with a detection limit of 2.6 ng/mL. This method relies on the nonspecific interaction between AuNPs and anti-IgG antibodies to realize sensitive detection of IgG and eliminates the use of detection antibodies. The concept is an alternative to many existing immunoassay technologies.

Portable and Flexible Hydrogel Sensor for On-Site Atrazine Assay on Agricultural Products.

There is growing attention focused toward the problems of ecological sustainability and food safety raised from the abuse of herbicides, which underscores the need for the development of a portable and reliable sensor for simple, rapid, and user-friendly on-site analysis of herbicide residues. Herein, a novel multifunctional hydrogel composite is explored to serve as a portable and flexible sensor for the facile and efficient analysis of atrazine (ATZ) residues. The hydrogel electrode is fabricated by doping graphite-phase carbon nitride (g-C3N4) into the aramid nanofiber reinforced poly(vinyl alcohol) hydrogel via a simple solution-casting procedure. Benefiting from the excellent electroactivity and large specific surface area of the solid nanoscale component, the prepared hydrogel sensor is capable of simple, rapid, and sensitive detection of ATZ with a detection limit down to 0.002 ng/mL and per test time less than 1 min. After combination with a smartphone-controlled portable electrochemical analyzer, the flexible sensor exhibited satisfactory analytical performance for the ATZ assay. We further demonstrated the applications of the sensor in the evaluation of the ATZ residues in real water and soil samples as well as the user-friendly on-site point-of-need detection of ATZ residues on various agricultural products. We envision that this flexible and portable sensor will open a new avenue on the development of next-generation analytical tools for herbicide monitoring in the environment and agricultural products.

Abstract PO2-15-02: Personalized circulating tumor DNA (ctDNA) monitoring can early identify disease progression and predict prognosis in patients with breast cancer undergoing neoadjuvant therapy

Abstract Background: Circulating tumor DNA (ctDNA) analysis offers a non-invasive method to assess tumor burden during treatment. Although some data have been reported on the use of ctDNA in neoadjuvant therapy (NAT) for breast cancer (BC), there is a lack of data on neoadjuvant efficacy and prognosis in China specifically using tumor-informed personalized ctDNA monitoring panel. Methods: We performed personalized ctDNA analyses at different time of NAT (before, during, and after) in 19 patients with Stage IIA-IIIB BC. WES was conducted on tumor tissues, and single nucleotide variants (SNVs) (20-40) were selected for each patient to ensure accurate and sensitive detection of individual ctDNA(Shanghai OrigiMed Co., Ltd.). Results: A total of 19 BC patients, 6 HER2-negative and 13 HER2-positive, were enrolled at the Breast Center, Fourth Hospital of Hebei Medical University (China) from June 2022 to May 2023. The median age of the patients was 53 (min-max: 28-64) years old. Through WES, it was discovered that 78.5% (3377/4303) of the mutated genes were unique to each patient. Additionally, 96.1% (637/663) of the selected tumor-informed SNVs were VUS variants. These findings suggest that tumor-informed ctDNA monitoring is more effective than panel-based ctDNA monitoring in BC. Among the patients, 84% (16/19) completed baseline blood collection, 63% (12/19) completed blood collection after NAT and 42% (8/12) patients completed blood collection after the surgery. The baseline positivity rate was 100%, and the baseline ctDNA variant allele frequency was significantly associated with T stage and N stage (both p < 0.01). This suggests that designing a panel based on puncture samples is feasible for ctDNA analysis. The detection of ctDNA before surgery after NAT correlated with the postoperative ctDNA status. Patients with persistently negative ctDNA during NAT were associated with pathologic complete response (pCR), although the difference was not statistically significant due to the small sample size (n=7). In 84% of patients, dynamic changes in ctDNA aligned with imaging findings, indicating a correlation between ctDNA and disease progression. A 56-year-old patient with HER2-negative stage IIIC BC had persistent ctDNA positivity during NAT. Imaging evaluation showed disease progression, with ctDNA allele frequency increasing 18 days before detection on imaging. After surgical tumor removal, the pathology assessment revealed a change in HER2 status from negative to positive. The patient received adjuvant chemotherapy combined with HER2-targeted therapy, resulting in a transition from positive to negative ctDNA status. The disease has remained stable for nearly 9 months. A 29-year-old patient with HER2-positive stage IIIA BC underwent NAT for 8 cycles. Due to drug intolerance, the treatment was interrupted multiple times during the first 4 cycles, and ctDNA remained positive. After modifying the treatment regimen in the 5th cycle, ctDNA became negative until the patient underwent surgery. The postoperative pathology evaluation revealed a pCR. Conclusions: Personalized ctDNA monitoring is more effective than panel-based ctDNA (a predefined set of cancer-associated genes) monitoring in BC. The status of ctDNA before and after surgery following NAT may be correlated, suggesting that patients with positive ctDNA before surgery may benefit from intensive therapy. More importantly, dynamic changes in ctDNA closely align with radiological findings, enabling early detection of disease progression and guiding treatment modifications. Citation Format: Yunjiang Liu, Chao Shi, Xiangmei Zhang, Xiaofei Ren, Shang Wu, Yaxian Wang, Yue Che, Zanmei Xu, Fei Pang. Personalized circulating tumor DNA (ctDNA) monitoring can early identify disease progression and predict prognosis in patients with breast cancer undergoing neoadjuvant therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-15-02.

Ultra-highly sensitive dual gases detection based on photoacoustic spectroscopy by exploiting a long-wave, high-power, wide-tunable, single-longitudinal-mode solid-state laser.

Photoacoustic spectroscopy (PAS) as a highly sensitive and selective trace gas detection technique has extremely broad application in many fields. However, the laser sources currently used in PAS limit the sensing performance. Compared to diode laser and quantum cascade laser, the solid-state laser has the merits of high optical power, excellent beam quality, and wide tuning range. Here we present a long-wave, high-power, wide-tunable, single-longitudinal-mode solid-state laser used as light source in a PAS sensor for trace gas detection. The self-built solid-state laser had an emission wavelength of ~2 μm with Tm:YAP crystal as the gain material, with an excellent wavelength and optical power stability as well as a high beam quality. The wide wavelength tuning range of 9.44 nm covers the absorption spectra of water and ammonia, with a maximum optical power of ~130 mW, allowing dual gas detection with a single laser source. The solid-state laser was used as light source in three different photoacoustic detection techniques: standard PAS with microphone, and external- and intra-cavity quartz-enhanced photoacoustic spectroscopy (QEPAS), proving that solid-state laser is an attractive excitation source in photoacoustic spectroscopy.

The layer-by-layer assembled ERGO+/ERGO− multilayer modified electrode for sensitive detection of dopamine

Graphene materials represented by graphene oxide (GO) have been widely regarded as functional coatings or films to modify surface of the electrode for detecting dopamine molecules. However, interfacial material properties for detection sensitivity, film stability, and applicability to electrodes are still highly desired. Herein, we first present a screen-printing carbon electrode (SPCE) coated with an electrochemically reduced layer-by-layer (LbL) assembled multilayer driven by an electrostatic interaction between positively charged polyethyleneimine-modified GO with amine groups (ERGO+) and negatively charged carboxyl-functionalized GO (ERGO−), which is briefly described as (ERGO+/ERGO−)n/SPCE. Firstly, without using conventional glassy carbon and gold electrodes, SPCE was tried to make coatings adapt to more flexible and unstable electrodes, simultaneously guaranteeing higher detection performance. Secondly, although a variety of electrochemical sensors such as GO−/SPCE and ERGO−/SPCE were obtained through the drop-casting technique, as-prepared (ERGO+/ERGO−)n/SPCE showed much higher electrocatalytic activities with enhanced peak current signals and reduced charge transfer resistance. Finally, excellent electrochemical properties and sensing performances of the (ERGO+/ERGO−)n/SPCE sensor for detection of dopamine were demonstrated, especially having a linear range of 1 μM to 1000 μM. Meanwhile, the detection limit is as low as 0.39 μM and S/N is equal to 3. The present work offers a potential direction to develop GO modified electrodes for sensitive biomolecular detection.

Enhancing the O2 sensitivity of [Ru(bpy)3]2+ dye by incorporating SnO2 and Ni:SnO2

Oxygen (O2)-sensitive probes encapsulated in a polymeric matrix have gas sensitivity improved by adding different metal oxide semiconductors (MOSs) to the composition. In this research, O2-sensitive tris(2,2′-bipyridyl) ruthenium(II) chloride ([Ru(bpy)3]Cl2) was chosen as a fluorophore, and SnO2 and Ni:SnO2 additives were used to enhance the oxygen sensitivity of the dye. While preparing sensing agents as a form of thin film and nanofiber, dye and MOSs powders were immobilized into the polymethylmethacrylate (PMMA) matrix in close proximity to each other. The oxygen-induced intensity measurements, decay time kinetics, and kinetic response were investigated for each of the sensing slides in the concentration range of 0–100% [O2]. Signal decreases in the emission-based intensity values of all MOSs-doped [Ru(bpy)3]2+-based complexes were monitored. Compared with free form, Ni:SnO2-doped [Ru(bpy)3]2+-based nanofiber agents exhibited a 4.03-fold increase in signal change (I0/I) ratio. The nanofiber structure, which allows the sensor slide to have a higher surface/volume ratio, allows O2 gas to penetrate more effectively. This can lead to greater interaction of the gas within the sensor matrix, resulting in more sensitive detection. Higher Stern Volmer (Ksv) values, greater O2 -induced sensing capabilities, more linear spectral measurements over larger concentration ranges, and faster response and recovery times show that MOSs-doped [Ru(bpy)3]2+-based sensing agents make promising candidates as oxygen probes.

Enhancing the photoelectric performance of TiO2-based heterojunction using the hydrothermal decomposition of MIL-125 strategy for sensitive detection of Bisphenol A

Due to its outstanding conductive properties, TiO2-based heterojunctions have extensive applications in the field of photoelectrochemical sensors. However, due to surface energy and van der Waals forces, TiO2 tends to aggregate and presents an uneven distribution, which reduces the overall performance of these heterostructures. To overcome these challenges and achieve a uniform distribution of TiO2 within the heterojunction, the characteristic of gradual decomposition of the metal-organic framework MIL-125 under hydrothermal conditions was employed. This process gradually generates TiO2 particles that slowly participate in the construction of the heterojunction. By combining the exceptional light absorption properties and appropriate bandgap widths of CdS and CdIn2S4, a uniformly distributed flower-globular ternary heterojunction CdS/CdIn2S4/TiO2-FG was successfully synthesized. In comparison to the disordered heterojunction CdS/CdIn2S4/TiO2-DO, CdS/CdIn2S4/TiO2-FG exhibits enhanced visible light absorption properties and photoelectric conversion efficiency. Taking Bisphenol A (BPA) as a model, a signal-off photoelectrochemical (PEC) aptasensor based on the CdS/CdIn2S4/TiO2-FG was established and exhibited a high sensitive detection for BPA with a linear response range from 10−1 to 107 pM, as well as an ultralow detection limit of 0.015 pM, revealing vivid selectivity, stability, and reproducibility. Therefore, this study offers an efficient and straightforward approach for the preparation of TiO2-based heterojunctions with superior photoelectric activity.

A remote-controlled portable workstation for highly sensitive and real-time chemiluminescent detection of cadmium

The prevention of pollution requires real-time monitoring of cadmium (Cd2+) concentration in the food, as it has a dramatic impact on poultry and can pose a threat to human health. Here, we fabricate a portable workstation integrating a microfluidic chip that facilitates real-time monitoring of Cd2+ levels in real samples by utilizing the Luminol-KMnO4 chemiluminescence (CL) system. Interestingly, Cd2+ can significantly enhance the CL signal, resulting in sensitive detection of Cd2+ in the range of 0–0.18 mg/L with the limit of detection (LOD) of 0.207 μg/L. Furthermore, a remote-controlled unit is integrated into the portable workstation to form a remote-controlled portable workstation (RCPW) performing automated point-of-care testing (POCT) of Cd2+. The as-prepared strategy allows remote control of RCPW to avoid long-distance transportation of samples to achieve real-time target monitoring. Consequently, this system furnishes RCPW for monitoring Cd2+ levels in real samples, thereby holding potential for applications in preventing food pollution.

Snowflake Cu2S@ZIF-67: A Novel Heterostructure Substrate for Enhanced Adsorption and Sensitive Detection in SERS

Snowflake Cu2S@ZIF-67: A Novel Heterostructure Substrate for Enhanced Adsorption and Sensitive Detection in SERS

Sensitive detection of kanamycin based on ECL resonance energy transfer between iridium complex doped SiO2 nanospheres and Au nanoparticles decorated TiVC MXene

Herein, a novel sandwich electrochemiluminescence (ECL) aptasensor was developed based on the resonance energy transfer (RET) with iridium complex doped silicate nanoparticles (SiO2@Ir) as energy donor and gold nanoparticles modified TiVC MXene (AuNPs@TiVC) as energy acceptor. Strong anodic ECL signal of SiO2@Ir was obtained through both co-reactant pathway and annihilation pathway. Electrochemical results showed that SiO2@Ir has good electron transfer rate and large specific surface area to immobilize more aptamers. AuNPs@TiVC apparently quenched the ECL signal of SiO2@Ir due to the ECL resonance energy transfer between them. In the presence of kanamycin (KAN), a sandwich type sensor was formed with the aptamer probes as connecters between the donor and the acceptor, resulting in the decrease of ECL intensity. Under the optimal condition, KAN could be sensitively detected in the range of 0.1 pg/mL to 10 ng/mL with a low detection limit of 24.5 fg/mL. The proposed ECL system exhibited satisfactory analytical performance, which can realize the detection of various biological molecules by adopting suitable aptamer.

Proteolytic reaction-based versatile electrochemical biosensor chip for simple and quantitative point-of-care testing

Electrochemical protease biosensors are well-suited for simple and quantitative point-of-care testing. However, there has been limited development of versatile chip formats similar to lateral-flow and glucose test strips for electrochemical proteases biosensors. This paper presents a versatile electrochemical biosensor chip for the wash-free and sensitive detection of proteases. The chip comprises (i) a reaction well, (ii) micropatterned electrodes on a glass substrate, and (iii) target protease-dependent filter paper. All (bio)chemicals required for the proteolytic reaction and signal amplification were predried on filter paper, which was then placed inside the reaction well. Upon injecting the sample solution into the reaction well, most of the dried (bio)chemicals dissolved rapidly. Wash-free and sensitive protease detection was achieved using electrochemical-enzymatic (EN) redox cycling of a redox-active species (4-amino-1-naphthol, AN) liberated from a peptide substrate through a rapid proteolytic reaction. The EN redox cycling involves a working electrode, AN, glucose dehydrogenase, and glucose. To enhance dissolvability and stability, (bio)chemicals were dried using a surfactant and stabilizer and stored at 4 °C with vacuum sealing. To minimize the effect of background variation among the different samples, a high concentration of glucose (200mM) was used, and the difference between the two charge values obtained before and after the incubation period was measured. The biosensor chips successfully detected three proteases: thrombin, leucine aminopeptidase (LAP), and 3CL protease from coronavirus SARS-CoV-2 (Mpro). The detection limits of thrombin in artificial serum, Mpro in artificial saliva, and LAP in human serum were approximately 100, 100pg/mL, and 8U/L, respectively.

Sensitive detection of exosomes by an electrochemical aptasensor based on double nucleic acid amplifications

Exosomes are extracellular vesicles secreted by mammalian cells and recognized as a powerful non-invasive cancer marker because they carry the cellular components specific to parent cells. The development of a convenient, rapid and sensitive exosome detection method is very important for the early diagnosis of cancer. In this study, an electrochemical biosensor based on two signal amplification methods, primer exchange reaction (PER) and rolling circle amplification (RCA), was developed for the high sensitive detection of exosomes. First, exosomes were specifically captured by CD63 aptamer and DNA strands (T) were released through a chain replacement reaction. Then the T strands initiated the PER reaction, producing a large number of short strands of DNA (P). Afterwards, RCA reaction was carried out on the electrode surface. Finally, a large amount of horseradish peroxidase (HRP) was bound to the electrode surface to catalyze o-phenylenediamine (OPD) oxidation, and the reduction current signal was obtained to realize the quantitative detection of exosomes. Under the optimal experimental conditions, there was a good linear relationship between DPV signal and the logarithm of exosome concentration in the range of 88 ∼ 8.8 × 106 particle/μL with a low limit of detection of 22 particle/μL. This strategy could realize sensitive detection of exosomes and provide a new strategy for the detection of other tumor markers.

Porphyrin-based covalent organic framework as oxidase mimic for highly sensitive colorimetric detection of pesticides.

A covalent organic framework-based strategy was designedfor label-free colorimetric detection of pesticides. Covalent organic framework-based nanoenzyme with excellent oxidase-like catalytic activity was synthesized. Unlike other artificial enzymes, porphyrin-based covalent organic framework (p-COF) as the oxidase mimic showed highly catalytic chromogenic activity and good affinity toward TMB without the presence of H2O2, which can be used as substitute for peroxidase mimics and H2O2 system in the colorimetric reaction. Based on the fact that the pesticide-aptamer complex can inhibit the oxidase activity of p-COF and reduced the absorbance at 650nm in UV-Vis spectrum, a label-free and facile colorimetric detection of pesticides was designed and fabricated. Under the optimized conditions, the COF-based colorimetric probe for pesticide detection displayed high sensitivity and selectivity. Taking fipronil for example the limit of detection was 2.7ng/mL and the linear range was 5-500,000ng/mL. The strategy was successfully applied to the detection of pesticides with good recovery , which was in accordance with that of HPLC-MS/MS. The COF-based colorimetric detection was free of complicated modification H2O2, which guaranteed the accuracy and reliability of measurements. The COF-based sensing strategy is a potential candidate for the sensitive detection of pesticides of interests.

ECL cytosensor for sensitive and label-free detection of circulating tumor cells based on hierarchical flower-like gold microstructures

The development of sensitive and efficient cell sensing strategies to detect circulating tumor cells (CTCs) in peripheral blood is crucial for the early diagnosis and prognostic assessment of cancer clinical treatment. Herein, an array of hierarchical flower-like gold microstructures (HFGMs) with anisotropic nanotips was synthesized by a simple electrodeposition method and used as a capture substrate to construct an ECL cytosensor based on the specific recognition of target cells by aptamers. The complex topography of the HFGMs array not only catalyzed the enhancement of ECL signals, but also induced the cells to generate more filopodia, improving the capture efficiency and shortening the capture time. The effect of topographic roughness on cell growth and adhesion propensity was also investigated, while the cell capture efficiency was proposed to be an important indicator affecting the accuracy of the ECL cytosensor. In addition, the capture of cells on the electrode surface increased the steric hindrance, which caused ECL signal changes in the Ru(bpy)32+ and TPrA system, realizing the quantitative detection of MCF-7 cells. The detection range of the sensor was from 102 to 106 cells mL−1 and the detection limit was 18 cells mL−1. The proposed detection method avoids the process of separation, labeling and counting, which has great potential for sensitive detection in clinical applications.