-
Science Advances Oct 2021Actinium-based therapies could revolutionize cancer medicine but remain tantalizing due to the difficulties in studying and limited knowledge of Ac chemistry. Current...
Actinium-based therapies could revolutionize cancer medicine but remain tantalizing due to the difficulties in studying and limited knowledge of Ac chemistry. Current efforts focus on small synthetic chelators, limiting radioisotope complexation and purification efficiencies. Here, we demonstrate a straightforward strategy to purify medically relevant radiometals, actinium(III) and yttrium(III), and probe their chemistry, using the recently discovered protein, lanmodulin. The stoichiometry, solution behavior, and formation constant of the Ac-lanmodulin complex and its Y/Y/La analogs were experimentally determined, representing the first actinium-protein and strongest actinide(III)-protein complex (sub-picomolar ) to be characterized. Lanmodulin’s unparalleled properties enable the facile purification recovery of radiometals, even in the presence of >10 equivalents of competing ions and at ultratrace levels: down to 2 femtograms Y and 40 attograms Ac. The lanmodulin-based approach charts a new course to study elusive isotopes and develop versatile chelating platforms for medical radiometals, both for high-value separations and potential in vivo applications.
PubMed: 34669462
DOI: 10.1126/sciadv.abk0273 -
Nano Letters Sep 2023Molecular-level spectroscopy is crucial for sensing and imaging applications, yet detecting and quantifying minuscule quantities of chemicals remain a challenge,...
Molecular-level spectroscopy is crucial for sensing and imaging applications, yet detecting and quantifying minuscule quantities of chemicals remain a challenge, especially when they surface adsorb in low numbers. Here, we introduce a photothermal spectroscopic technique that enables the high selectivity sensing of adsorbates with an attogram detection limit. Our approach utilizes the Seebeck effect in a microfabricated nanoscale thermocouple junction, incorporated into the apex of a microcantilever. We observe minimal thermal mass exhibited by the sensor, which maintains exceptional thermal insulation. The temperature variation driving the thermoelectric junction arises from the nonradiative decay of molecular adsorbates' vibrational states on the tip. We demonstrate the detection of photothermal spectra of physisorbed trinitrotoluene (TNT) and dimethyl methylphosphonate (DMMP) molecules, as well as representative polymers, with an estimated mass of 10 g.
PubMed: 37579260
DOI: 10.1021/acs.nanolett.3c01710 -
IScience Feb 2023The inherent properties of 2D materials-light mass, high out-of-plane flexibility, and large surface area-promise great potential for precise and accurate nanomechanical...
The inherent properties of 2D materials-light mass, high out-of-plane flexibility, and large surface area-promise great potential for precise and accurate nanomechanical mass sensing, but their application is often hampered by surface contamination. Here we demonstrate a tri-layer graphene nanomechanical resonant mass sensor with sub-attogram resolution at room temperature, fabricated by a bottom-up process. We found that Joule-heating is effective in cleaning the graphene membrane surface, which results in a large improvement in the stability of the resonance frequency. We characterized the sensor by depositing Cr metal using a stencil mask and found a mass-resolution that is sufficient to weigh very small particles, like large proteins and protein complexes, with potential applications in the fields of nanobiology and medicine.
PubMed: 36718371
DOI: 10.1016/j.isci.2023.105958 -
Analytical Chemistry Mar 2023Although thermal ionization mass spectrometry (TIMS) has been employed for the high-precision analysis of isotope ratios, direct quantification of artificial...
Direct Quantification of Attogram Levels of Strontium-90 in Microscale Biosamples Using Isotope Dilution-Thermal Ionization Mass Spectrometry Assisted by Quadrupole Energy Filtering.
Although thermal ionization mass spectrometry (TIMS) has been employed for the high-precision analysis of isotope ratios, direct quantification of artificial mono-nuclide in the environment is difficult by even using isotope dilution (ID) due to the coexistence of the great magnitude of natural stable nuclides or isobars. In traditional TIMS and ID-TIMS, a sufficient amount of stable Sr doped on a filament is required to realize a stable and adequate ion-beam intensity (i.e., thermally ionized beams). However, the background noise (BGN) at / 90, detected by an electron multiplier, disturbs Sr analysis at low concentration levels due to peak tailing of a significant Sr ion beam dependent on the Sr-doping amount. Here, TIMS assisted by quadruple energy filtering was successfully employed for the direct quantification of attogram levels of an artificial monoisotopic radionuclide strontium-90 (Sr) in microscale biosamples. Direct quantification was achieved by integrating the ID quantification of natural Sr and simultaneous Sr/Sr isotope ratio analysis. Additionally, the measurement amount calculated by the combination of the ID and intercalibration was corrected for the net result amount of Sr by subtracting dark noise and the detected amount derived from the survived Sr, which are equivalent with the BGN intensity at / 90. Background correction revealed that the detection limits were in the range of 6.15 × 10-3.90 × 10 ag (0.31-1.95 μBq), depending on the concentration of natural Sr in a 1 μL sample, and the quantification of 0.98 ag (5.0 μBq) of Sr in 0-300 mg/L of natural Sr was successful. This method could analyze small sample quantities (1 μL), and the quantitative results were verified against authorized radiometric analysis techniques. Furthermore, the amount of Sr in actual teeth was successfully quantified. This method will be a powerful tool for measuring Sr in the measurement of micro-samples, which are required to assess and understand the degree of internal radiation exposure.
PubMed: 36906855
DOI: 10.1021/acs.analchem.2c04844 -
Microsystems & Nanoengineering 2022The use of nanoparticles has been growing in various industrial fields, and concerns about their effects on health and the environment have been increasing. Hence,...
The use of nanoparticles has been growing in various industrial fields, and concerns about their effects on health and the environment have been increasing. Hence, characterization techniques for nanoparticles are essential. Here, we present a silicon dioxide microfabricated suspended microchannel resonator (SMR) to measure the mass and concentration of nanoparticles in a liquid as they flow. We measured the mass detection limits of the device using laser Doppler vibrometry. This limit reached a minimum of 377 ag that correspond to a 34 nm diameter gold nanoparticle or a 243 nm diameter polystyrene particle, when sampled every 30 ms. We compared the fundamental limits of the measured data with an ideal noiseless measurement of the SMR. Finally, we measured the buoyant mass of gold nanoparticles in real-time as they flowed through the SMR.
PubMed: 36051745
DOI: 10.1038/s41378-022-00425-8 -
Frontiers in Molecular Biosciences 2022Thrips cause considerable economic losses to a wide range of food, feed, and forest crops. They also transmit several plant viruses. Being cryptic, it is often difficult...
Thrips cause considerable economic losses to a wide range of food, feed, and forest crops. They also transmit several plant viruses. Being cryptic, it is often difficult to distinguish thrips species in crops and large consignments by conventional methods. Melon thrips ( Karny, Thysanoptera: Thripidae) is an invasive insect pest of vegetables, legumes, and ornamentals besides being vector to several viruses. It poses a threat to domestic and international plant biosecurity and can invade and establish in new areas. Here, we report a polymerase spiral reaction (PSR)-based isothermal assay for rapid, sensitive, specific, low-cost, and on-site detection of . To the best of our knowledge, this is the first application of PSR in the identification of any insect species. A primer pair designed based on 3'-polymorphism of mtCOIII region can specifically identify without any cross-reactivity with predominant thrips species. The assay uses crude lysate of a single thrips saving time and reagents involved in nucleic acid extraction. The presence of is visualized by the appearance of bright fluorescence under ultraviolet light or a change in reaction color thus avoiding gel electrophoresis steps. The entire process can be completed in 70 min on-site using only an ordinary water bath. The assay is sensitive to detecting as little as 50 attograms of template. The assay was validated with known thrips specimens and found to be efficient in diagnosing under natural conditions. The described method will be useful for non-expert personnel to detect an early infestation, accidental introduction to a new area, restrict the spread of diseases and formulate appropriate management strategies.
PubMed: 35586189
DOI: 10.3389/fmolb.2022.853339 -
Langmuir : the ACS Journal of Surfaces... Jan 2021Bacterial endotoxin detection is an essential safety requisite in biomedical, food, and pharmaceutical industries. Endotoxin in a sufficient concentration on entering...
Bacterial endotoxin detection is an essential safety requisite in biomedical, food, and pharmaceutical industries. Endotoxin in a sufficient concentration on entering the human bloodstream causes detrimental effects such as septic shock, which can lead to death. Hence, the sensitive and selective detection of endotoxin also known as lipopolysaccharide (LPS) is of paramount importance. Herein, a layer-by-layer (LBL) assembly of gold-chitosan nanocomposite (CGNC)-poly(acrylic acid) (PAA)-polymyxin B (PmB) on gold (Au) electrode is employed for the sensitive and selective detection of endotoxin. The surface electric charge studies using dynamic contact mode electrostatic force microscopy (DC-EFM) revealed the successful formation of each layer on the Au electrode. The polycationic PmB is a specific bioreceptor of LPS, which binds with high affinity to the anionic groups of the carbohydrate portions of LPS molecules and facilitates the selective electrochemical detection. This surface modification method presented a sensitive and selective detection of endotoxin down to the attogram level.
PubMed: 33356305
DOI: 10.1021/acs.langmuir.0c02852 -
Scientific Reports Jul 2021In the present article, we developed a highly sensitive label-free electrochemical immunosensor based on NiFe-layered double hydroxides (LDH)/reduced graphene oxide...
In the present article, we developed a highly sensitive label-free electrochemical immunosensor based on NiFe-layered double hydroxides (LDH)/reduced graphene oxide (rGO)/gold nanoparticles modified glassy carbon electrode for the determination of receptor tyrosine kinase-like orphan receptor (ROR)-1. In this electrochemical immunoassay platform, NiFe-LDH/rGO was used due to great electron mobility, high specific surface area and flexible structures, while Au nanoparticles were prepared and coated on the modified electrodes to improve the detection sensitivity and ROR1 antibody immobilizing (ROR1Ab). The modification procedure was approved by using cyclic voltammetry and differential pulse voltammetry based on the response of peak current to the step by step modifications. Under optimum conditions, the experimental results showed that the immunosensor revealed a sensitive response to ROR1 in the range of 0.01-1 pg mL, and with a lower limit of quantification of 10 attogram/mL (10 ag mL). Furthermore, the designed immunosensor was applied for the analysis of ROR1 in several serum samples of chronic lymphocytic leukemia suffering patients with acceptable results, and it also exhibited good selectivity, reproducibility and stability.
Topics: Biomarkers; Biosensing Techniques; Electrochemical Techniques; Female; Ferric Compounds; Gold; Graphite; Humans; Hydroxides; Immunoassay; Leukemia, Lymphocytic, Chronic, B-Cell; Limit of Detection; Male; Metal Nanoparticles; Nanocomposites; Nickel; Receptor Tyrosine Kinase-like Orphan Receptors; Reproducibility of Results
PubMed: 34290319
DOI: 10.1038/s41598-021-94380-5 -
Frontiers in Cellular and Infection... 2023Periprosthetic joint infection (PJI) can be diagnosed to characterize the microorganisms constituting a biofilm, which is an essential procedure for proper treatment....
Periprosthetic joint infection (PJI) can be diagnosed to characterize the microorganisms constituting a biofilm, which is an essential procedure for proper treatment. The gold standard method for detecting and identifying the causative microorganism is culture of microorganisms from patients-derived sample.; however, this method takes a long time and has low sensitivity. To compensate for these limitations, identification methods based on real-time PCR (RT-PCR) have been widely used. However, RT-PCR also has limitations, including low sensitivity and the requirement of a standard curve for quantification. Therefore, to prevent significant proliferation of pathogenic bacteria, it is important to detect a limited number of infectious bacteria during early stages of PJI. In the present study, we developed droplet digital PCR-based detection of bacterial pathogens in PJI. And we evaluated the analytical performance of the assay using a model plasmid, based on the 16S ribosomal DNA sequence of target bacteria commonly found in PJI. We also prepared genomic DNA extracted from , , and to test whether ddPCR provides better sensitivity and quantification of the target sequences. ddPCR detected 400 attograms of target DNA, which was more than 10 times less than that detected by real-time PCR using synthesized plasmid. In addition, ddPCR detected target regions from genomic DNA of 50 femtograms for , 70 femtograms for , and 90 femtograms for . The results indicate that ddPCR has the potential to decrease the microbial detection limit and provide precise detection, signifying its effectiveness for early PJI.
Topics: Humans; Escherichia coli; Staphylococcus aureus; Plasmids; Bacteria; Arthritis, Infectious; Real-Time Polymerase Chain Reaction; DNA, Ribosomal
PubMed: 38029245
DOI: 10.3389/fcimb.2023.1301446 -
ACS Sensors Apr 2020As the use of nanoparticles is expanding in many industrial sectors, pharmaceuticals, cosmetics among others, flow-through characterization techniques are often required...
As the use of nanoparticles is expanding in many industrial sectors, pharmaceuticals, cosmetics among others, flow-through characterization techniques are often required for in-line metrology. Among the parameters of interest, the concentration and mass of nanoparticles can be informative for yield, aggregates formation or even compliance with regulation. The Suspended Nanochannel Resonator (SNR) can offer mass resolution down to the attogram scale precision in a flow-through format. However, since the readout has been based on the optical lever, operating more than a single resonator at a time has been challenging. Here we present a new architecture of SNR devices with piezoresistive sensors that allows simultaneous readout from multiple resonators. To enable this architecture, we push the limits of nanofabrication to create implanted piezoresistors of nanoscale thickness (∼100 nm) and implement an algorithm for designing SNRs with dimensions optimized for maintaining attogram scale precision. Using 8-in. processing technology, we fabricate parallel array SNR devices which contain ten resonators. While maintaining a precision similar to that of the optical lever, we demonstrate a throughput of 40 000 particles per hour-an order of magnitude improvement over a single device with an analogous flow rate. Finally, we show the capability of the SNR array device for measuring polydisperse solutions of gold particles ranging from 20 to 80 nm in diameter. We envision that SNR array devices will open up new possibilities for nanoscale metrology by measuring not only synthetic but also biological nanoparticles such as exosomes and viruses.
Topics: Gold; Microfluidic Analytical Techniques; Nanoparticles
PubMed: 32233476
DOI: 10.1021/acssensors.0c00394