Biochemistry, Genetics and Molecular Biology Molecular Biology

Advanced biosensing and bioanalysis techniques

Description

This cluster of papers focuses on the use of DNA as a versatile tool for creating nanoscale shapes, self-assembled structures, and functional biomolecular devices. It explores applications in biosensors, aptamers, nanoparticle-based bio-barcode detection, electrochemistry, and cancer diagnostics.

Keywords

DNA nanotechnology; self-assembly; biosensors; aptamers; nanoparticles; electrochemistry; molecular machines; nanoscale shapes; biomolecular interactions; cancer diagnostics

Research Article| February 01 1956 A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid K. Burton K. Burton 1Medical Research Council, … Research Article| February 01 1956 A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid K. Burton K. Burton 1Medical Research Council, Cell Metabolism Research Unit, Department of Biochemistry, University of Oxford Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd © 1956 CAMBRIDGE UNIVERSITY PRESS1956 Biochem J (1956) 62 (2): 315–323. https://doi.org/10.1042/bj0620315 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation K. Burton; A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 1 February 1956; 62 (2): 315–323. doi: https://doi.org/10.1042/bj0620315 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1956 CAMBRIDGE UNIVERSITY PRESS1956 Article PDF first page preview Close Modal You do not currently have access to this content.
ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTNew Strategies for Fluorescent Probe Design in Medical Diagnostic ImagingHisataka Kobayashi*†, Mikako Ogawa†, Raphael Alford†, Peter L. Choyke†, and Yasuteru Urano‡View Author Information Molecular Imaging Program, Center … ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTNew Strategies for Fluorescent Probe Design in Medical Diagnostic ImagingHisataka Kobayashi*†, Mikako Ogawa†, Raphael Alford†, Peter L. Choyke†, and Yasuteru Urano‡View Author Information Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1088, and Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan* To whom correspondence should be addressed. Phone: 301-451-4220. Fax: 301-402-3191. E-mail: [email protected]†National Institutes of Health.‡The University of Tokyo.Cite this: Chem. Rev. 2010, 110, 5, 2620–2640Publication Date (Web):December 15, 2009Publication History Received2 August 2009Published online15 December 2009Published inissue 12 May 2010https://doi.org/10.1021/cr900263jCopyright © 2009 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views30703Altmetric-Citations1749LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (4 MB) Get e-AlertsSUBJECTS:Biological imaging,Fluorescence,Imaging probes,Peptides and proteins,Probes Get e-Alerts
Multiplexed detection of oligonucleotide targets has been performed with gold nanoparticle probes labeled with oligonucleotides and Raman-active dyes. The gold nanoparticles facilitate the formation of a silver coating that acts … Multiplexed detection of oligonucleotide targets has been performed with gold nanoparticle probes labeled with oligonucleotides and Raman-active dyes. The gold nanoparticles facilitate the formation of a silver coating that acts as a surface-enhanced Raman scattering promoter for the dye-labeled particles that have been captured by target molecules and an underlying chip in microarray format. The strategy provides the high-sensitivity and high-selectivity attributes of gray-scale scanometric detection but adds multiplexing and ratioing capabilities because a very large number of probes can be designed based on the concept of using a Raman tag as a narrow-band spectroscopic fingerprint. Six dissimilar DNA targets with six Raman-labeled nanoparticle probes were distinguished, as well as two RNA targets with single nucleotide polymorphisms. The current unoptimized detection limit of this method is 20 femtomolar.
Nanorobots Deliver DNA aptamers are short strands that have high binding affinity for a target protein that can be used as triggers for releasing cargo from delivery vehicles. Douglas et … Nanorobots Deliver DNA aptamers are short strands that have high binding affinity for a target protein that can be used as triggers for releasing cargo from delivery vehicles. Douglas et al. (p. 831 ) used this strategy to design DNA origami “nanorobots”—complex shaped structures created by manipulating a long DNA strand through binding with shorter “staple” strands—that could deliver payloads such as gold nanoparticles or fluorescently labeled antibody fragments. These nanorobots were designed to open in response to specific cell-surface proteins, releasing molecules that triggered cell signaling.
Selective colorimetric polynucleotide detection based on Au nanoparticle probes which align in a "tail-to-tail" fashion onto a target polynucleotide is described. In this new nanoparticle-based detection system, Au particles (∼13 … Selective colorimetric polynucleotide detection based on Au nanoparticle probes which align in a "tail-to-tail" fashion onto a target polynucleotide is described. In this new nanoparticle-based detection system, Au particles (∼13 nm diameter), which are capped with 3'- and 5'-(alkanethiol)oligonucleotides, are used to complex a 24-base polynucleotide target. Hybridization of the target with the probes results in the formation of an extended polymeric Au nanoparticle/polynucleotide aggregate, which triggers a red to purple color change in solution. The color change is due to a red shift in the surface plasmon resonance of the Au nanoparticles. The aggregates exhibit characteristic, exceptionally sharp "melting transitions" (monitored at 260 or 700 nm), which allows one to distinguish target sequences that contain one base end mismatches, deletions, or an insertion from the fully complementary target. When test solutions are spotted onto a C18 reverse-phase thin-layer chromatography plate, color differentiation is enhanced and a permanent record of the test is obtained, thereby providing a better method for distinguishing the aforementioned target sequences. Significantly, one-pot colorimetric detection of the target in the presence of four strands with single base imperfections can be accomplished with this new probe system.
A highly selective, colorimetric polynucleotide detection method based on mercaptoalkyloligonucleotide-modified gold nanoparticle probes is reported. Introduction of a single-stranded target oligonucleotide (30 bases) into a solution containing the appropriate probes … A highly selective, colorimetric polynucleotide detection method based on mercaptoalkyloligonucleotide-modified gold nanoparticle probes is reported. Introduction of a single-stranded target oligonucleotide (30 bases) into a solution containing the appropriate probes resulted in the formation of a polymeric network of nanoparticles with a concomitant red-to-pinkish/purple color change. Hybridization was facilitated by freezing and thawing of the solutions, and the denaturation of these hybrid materials showed transition temperatures over a narrow range that allowed differentiation of a variety of imperfect targets. Transfer of the hybridization mixture to a reverse-phase silica plate resulted in a blue color upon drying that could be detected visually. The unoptimized system can detect about 10 femtomoles of an oligonucleotide.
ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTFunctional Nucleic Acid SensorsJuewen Liu, Zehui Cao, and Yi Lu*View Author Information Department of Chemistry, University of Illinois at Urbana—Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801* … ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTFunctional Nucleic Acid SensorsJuewen Liu, Zehui Cao, and Yi Lu*View Author Information Department of Chemistry, University of Illinois at Urbana—Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801* To whom correspondence should be addressed: Telephone: 217-333-2619. E-mail: [email protected]Cite this: Chem. Rev. 2009, 109, 5, 1948–1998Publication Date (Web):March 20, 2009Publication History Received10 January 2008Published online20 March 2009Published inissue 13 May 2009https://pubs.acs.org/doi/10.1021/cr030183ihttps://doi.org/10.1021/cr030183ireview-articleACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views34075Altmetric-Citations1929LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Fluorescence,Genetics,Metal nanoparticles,Peptides and proteins,Sensors Get e-Alerts
The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology … The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome. Progress towards cheaper and more compact DNA sequencing devices is limited by a number of factors, including the need for imaging technology. A new DNA sequencing technology that does away with optical readout, instead gathering sequence data by directly sensing hydrogen ions produced by template-directed DNA synthesis, offers a route to low cost and scalable sequencing on a massively parallel semiconductor-sensing device or ion chip. The reactions are performed using all natural nucleotides, and the individual ion-sensitive chips are disposable and inexpensive. The system has been used to sequence three bacterial genomes and a human genome: that of Gordon Moore of Moore's law fame.
Nanomaterials, such as metal or semiconductor nanoparticles and nanorods, exhibit similar dimensions to those of biomolecules, such as proteins (enzymes, antigens, antibodies) or DNA. The integration of nanoparticles, which exhibit … Nanomaterials, such as metal or semiconductor nanoparticles and nanorods, exhibit similar dimensions to those of biomolecules, such as proteins (enzymes, antigens, antibodies) or DNA. The integration of nanoparticles, which exhibit unique electronic, photonic, and catalytic properties, with biomaterials, which display unique recognition, catalytic, and inhibition properties, yields novel hybrid nanobiomaterials of synergetic properties and functions. This review describes recent advances in the synthesis of biomolecule-nanoparticle/nanorod hybrid systems and the application of such assemblies in the generation of 2D and 3D ordered structures in solutions and on surfaces. Particular emphasis is directed to the use of biomolecule-nanoparticle (metallic or semiconductive) assemblies for bioanalytical applications and for the fabrication of bioelectronic devices.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNanostructures in BiodiagnosticsNathaniel L. Rosi and Chad A. MirkinView Author Information Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113 Cite this: Chem. Rev. 2005, … ADVERTISEMENT RETURN TO ISSUEPREVArticleNanostructures in BiodiagnosticsNathaniel L. Rosi and Chad A. MirkinView Author Information Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113 Cite this: Chem. Rev. 2005, 105, 4, 1547–1562Publication Date (Web):March 23, 2005Publication History Received23 November 2004Published online23 March 2005Published inissue 1 April 2005https://pubs.acs.org/doi/10.1021/cr030067fhttps://doi.org/10.1021/cr030067fresearch-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views34466Altmetric-Citations4159LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Assays,Biopolymers,Genetics,Metal nanoparticles,Nanoparticles Get e-Alerts
We have developed a novel method, termed loop-mediated isothermal amplification (LAMP), that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions. This method employs a DNA polymerase and … We have developed a novel method, termed loop-mediated isothermal amplification (LAMP), that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions. This method employs a DNA polymerase and a set of four specially designed primers that recognize a total of six distinct sequences on the target DNA. An inner primer containing sequences of the sense and antisense strands of the target DNA initiates LAMP. The following strand displacement DNA synthesis primed by an outer primer releases a single-stranded DNA. This serves as template for DNA synthesis primed by the second inner and outer primers that hybridize to the other end of the target, which produces a stem-loop DNA structure. In subsequent LAMP cycling one inner primer hybridizes to the loop on the product and initiates displacement DNA synthesis, yielding the original stem-loop DNA and a new stem-loop DNA with a stem twice as long. The cycling reaction continues with accumulation of 10(9) copies of target in less than an hour. The final products are stem-loop DNAs with several inverted repeats of the target and cauliflower-like structures with multiple loops formed by annealing between alternately inverted repeats of the target in the same strand. Because LAMP recognizes the target by six distinct sequences initially and by four distinct sequences afterwards, it is expected to amplify the target sequence with high selectivity.
Antibodies, the most popular class of molecules providing molecular recognition needs for a wide range of applications, have been around for more than three decades. As a result, antibodies have … Antibodies, the most popular class of molecules providing molecular recognition needs for a wide range of applications, have been around for more than three decades. As a result, antibodies have made substantial contributions toward the advancement of diagnostic assays and have become indispensable in most diagnostic tests that are used routinely in clinics today. The development of the systematic evolution of ligands by exponential enrichment (SELEX) process, however, made possible the isolation of oligonucleotide sequences with the capacity to recognize virtually any class of target molecules with high affinity and specificity. These oligonucleotide sequences, referred to as "aptamers", are beginning to emerge as a class of molecules that rival antibodies in both therapeutic and diagnostic applications. Aptamers are different from antibodies, yet they mimic properties of antibodies in a variety of diagnostic formats. The demand for diagnostic assays to assist in the management of existing and emerging diseases is increasing, and aptamers could potentially fulfill molecular recognition needs in those assays. Compared with the bellwether antibody technology, aptamer research is still in its infancy, but it is progressing at a fast pace. The potential of aptamers may be realized in the near future in the form of aptamer-based diagnostic products in the market. In such products, aptamers may play a key role either in conjunction with, or in place of, antibodies. It is also likely that existing diagnostic formats may change according to the need to better harness the unique properties of aptamers.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSurface Plasmon Resonance Sensors for Detection of Chemical and Biological SpeciesJiří HomolaView Author Information Institute of Photonics and Electronics ASCR, Chaberská 57, 182 51 Prague 8, Czech … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSurface Plasmon Resonance Sensors for Detection of Chemical and Biological SpeciesJiří HomolaView Author Information Institute of Photonics and Electronics ASCR, Chaberská 57, 182 51 Prague 8, Czech Republic Cite this: Chem. Rev. 2008, 108, 2, 462–493Publication Date (Web):January 30, 2008Publication History Received31 May 2007Published online30 January 2008Published inissue 1 February 2008https://pubs.acs.org/doi/10.1021/cr068107dhttps://doi.org/10.1021/cr068107dresearch-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views32405Altmetric-Citations3416LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Biopolymers,Immunology,Peptides and proteins,Sensors,Surface plasmon resonance Get e-Alerts
Gold colloids have fascinated scientists for over a century and are now heavily utilized in chemistry, biology, engineering, and medicine. Today these materials can be synthesized reproducibly, modified with seemingly … Gold colloids have fascinated scientists for over a century and are now heavily utilized in chemistry, biology, engineering, and medicine. Today these materials can be synthesized reproducibly, modified with seemingly limitless chemical functional groups, and, in certain cases, characterized with atomic-level precision. This Review highlights recent advances in the synthesis, bioconjugation, and cellular uses of gold nanoconjugates. There are now many examples of highly sensitive and selective assays based upon gold nanoconjugates. In recent years, focus has turned to therapeutic possibilities for such materials. Structures which behave as gene-regulating agents, drug carriers, imaging agents, and photoresponsive therapeutics have been developed and studied in the context of cells and many debilitating diseases. These structures are not simply chosen as alternatives to molecule-based systems, but rather for their new physical and chemical properties, which confer substantive advantages in cellular and medical applications.
We present single-molecule, real-time sequencing data obtained from a DNA polymerase performing uninterrupted template-directed synthesis using four distinguishable fluorescently labeled deoxyribonucleoside triphosphates (dNTPs). We detected the temporal order of their … We present single-molecule, real-time sequencing data obtained from a DNA polymerase performing uninterrupted template-directed synthesis using four distinguishable fluorescently labeled deoxyribonucleoside triphosphates (dNTPs). We detected the temporal order of their enzymatic incorporation into a growing DNA strand with zero-mode waveguide nanostructure arrays, which provide optical observation volume confinement and enable parallel, simultaneous detection of thousands of single-molecule sequencing reactions. Conjugation of fluorophores to the terminal phosphate moiety of the dNTPs allows continuous observation of DNA synthesis over thousands of bases without steric hindrance. The data report directly on polymerase dynamics, revealing distinct polymerization states and pause sites corresponding to DNA secondary structure. Sequence data were aligned with the known reference sequence to assay biophysical parameters of polymerization for each template position. Consensus sequences were generated from the single-molecule reads at 15-fold coverage, showing a median accuracy of 99.3%, with no systematic error beyond fluorophore-dependent error rates.
Array technologies have made it straightforward to monitor simultaneously the expression pattern of thousands of genes. The challenge now is to interpret such massive data sets. The first step is … Array technologies have made it straightforward to monitor simultaneously the expression pattern of thousands of genes. The challenge now is to interpret such massive data sets. The first step is to extract the fundamental patterns of gene expression inherent in the data. This paper describes the application of self-organizing maps, a type of mathematical cluster analysis that is particularly well suited for recognizing and classifying features in complex, multidimensional data. The method has been implemented in a publicly available computer package, genecluster , that performs the analytical calculations and provides easy data visualization. To illustrate the value of such analysis, the approach is applied to hematopoietic differentiation in four well studied models (HL-60, U937, Jurkat, and NB4 cells). Expression patterns of some 6,000 human genes were assayed, and an online database was created. genecluster was used to organize the genes into biologically relevant clusters that suggest novel hypotheses about hematopoietic differentiation—for example, highlighting certain genes and pathways involved in “differentiation therapy” used in the treatment of acute promyelocytic leukemia.
Based on fundamental chemistry, biotechnology and materials science have developed over the past three decades into today's powerful disciplines which allow the engineering of advanced technical devices and the industrial … Based on fundamental chemistry, biotechnology and materials science have developed over the past three decades into today's powerful disciplines which allow the engineering of advanced technical devices and the industrial production of active substances for pharmaceutical and biomedical applications. This review is focused on current approaches emerging at the intersection of materials research, nanosciences, and molecular biotechnology. This novel and highly interdisciplinary field of chemistry is closely associated with both the physical and chemical properties of organic and inorganic nanoparticles, as well as to the various aspects of molecular cloning, recombinant DNA and protein technology, and immunology. Evolutionary optimized biomolecules such as nucleic acids, proteins, and supramolecular complexes of these components, are utilized in the production of nanostructured and mesoscopic architectures from organic and inorganic materials. The highly developed instruments and techniques of today's materials research are used for basic and applied studies of fundamental biological processes.
Solid-phase chemistry, photolabile protecting groups, and photolithography have been combined to achieve light-directed, spatially addressable parallel chemical synthesis to yield a highly diverse set of chemical products. Binary masking, one … Solid-phase chemistry, photolabile protecting groups, and photolithography have been combined to achieve light-directed, spatially addressable parallel chemical synthesis to yield a highly diverse set of chemical products. Binary masking, one of many possible combinatorial synthesis strategies, yields 2 n compounds in n chemical steps. An array of 1024 peptides was synthesized in ten steps, and its interaction with a monoclonal antibody was assayed by epifluorescence microscopy. High-density arrays formed by light-directed synthesis are potentially rich sources of chemical diversity for discovering new ligands that bind to biological receptors and for elucidating principles governing molecular interactions. The generality of this approach is illustrated by the light-directed synthesis of a dinucleotide. Spatially directed synthesis of complex compounds could also be used for microfabrication of devices.
Fluorometric hybridization in microdilution wells was developed to determine genetic relatedness among microorganisms. Total chromosomal deoxyribonucleic acid (DNA) for hybridization reactions was labeled with photoreactive biotin (photobiotin). The biotinylated DNA … Fluorometric hybridization in microdilution wells was developed to determine genetic relatedness among microorganisms. Total chromosomal deoxyribonucleic acid (DNA) for hybridization reactions was labeled with photoreactive biotin (photobiotin). The biotinylated DNA was hybridized with single-stranded unlabeled DNAs which had been immobilized on the surfaces of microdilution wells. After hybridization, biotinylated DNA was quantitatively detected with beta-D-galactosidase and a fluorogenic substrate, 4-methylumbelliferyl-beta-D-galactopyranoside. Homology values obtained with this fluorometric direct binding method were compared with values obtained with two membrane filter methods, one in which photobiotin labeling was used and one in which radioisotope labeling was used. The results showed that the fluorometric direct binding method in which microdilution wells are used could be an alternative to radioisotope and membrane filter hybridization methods.
A method for analyzing combinatorial DNA arrays using oligonucleotide-modified gold nanoparticle probes and a conventional flatbed scanner is described here. Labeling oligonucleotide targets with nanoparticle rather than fluorophore probes substantially … A method for analyzing combinatorial DNA arrays using oligonucleotide-modified gold nanoparticle probes and a conventional flatbed scanner is described here. Labeling oligonucleotide targets with nanoparticle rather than fluorophore probes substantially alters the melting profiles of the targets from an array substrate. This difference permits the discrimination of an oligonucleotide sequence from targets with single nucleotide mismatches with a selectivity that is over three times that observed for fluorophore-labeled targets. In addition, when coupled with a signal amplification method based on nanoparticle-promoted reduction of silver(I), the sensitivity of this scanometric array detection system exceeds that of the analogous fluorophore system by two orders of magnitude.
ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTLuminescent Chemodosimeters for BioimagingYuming Yang†, Qiang Zhao‡, Wei Feng†, and Fuyou Li*†View Author Information† Department of Chemistry and State Key Laboratory of Molecular Engineering of Polymers and … ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTLuminescent Chemodosimeters for BioimagingYuming Yang†, Qiang Zhao‡, Wei Feng†, and Fuyou Li*†View Author Information† Department of Chemistry and State Key Laboratory of Molecular Engineering of Polymers and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, P. R. China‡ Key Laboratory for Organic Electronics and Information Displays (KLOEID) and Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210046, P. R. China.*Fax: 86-21-55664621. Tel.: 86-21-55664185. E-mail: [email protected]Cite this: Chem. Rev. 2013, 113, 1, 192–270Publication Date (Web):June 18, 2012Publication History Received27 October 2011Published online18 June 2012Published inissue 9 January 2013https://pubs.acs.org/doi/10.1021/cr2004103https://doi.org/10.1021/cr2004103review-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views31453Altmetric-Citations2087LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Fluorescence,Fluorescence detection,Ions,Luminescence,Mercury Get e-Alerts
Abstract Leukemia, a prevalent form of cancer in both children and adults, remains a significant healthcare challenge despite advancements in understanding its molecular biology and treatment strategies. Early detection is … Abstract Leukemia, a prevalent form of cancer in both children and adults, remains a significant healthcare challenge despite advancements in understanding its molecular biology and treatment strategies. Early detection is paramount for improving patient outcomes, and conventional diagnostic methods often fall short in sensitivity or specificity. Nanosensors are miniature devices capable of detecting various physical or chemical characteristics at the nanoscale. Their unique properties, including vast surface area and high electrical conductivity, make them ideal for developing highly sensitive biosensors for cancer biomarker detection. By integrating nanomaterials as transducers or amplifiers within biosensor systems, researchers are creating novel tools for the early detection of leukemia‐related biomarkers in blood samples. These biosensors hold immense promise for noninvasive and real‐time monitoring of cancer progression, enabling prompt intervention and personalized treatment strategies. The review delves into the different types of nanomaterials used for constructing nanosensors for leukemia monitoring, including liposomes, polymeric nanoparticles and inorganic nanoparticles. It explores the advantages and disadvantages of each type of nanomaterial for this application. Additionally, the review discusses the design principles and fabrication methods used to create nanosensors, highlighting the challenges and opportunities associated with this technology.
Abstract Tumor‐derived biomarkers can precisely reflect cell types, offering major potential for early detection and therapy. An engineered platform capable of distinguishing various biomarkers for cancer type identification and autonomous … Abstract Tumor‐derived biomarkers can precisely reflect cell types, offering major potential for early detection and therapy. An engineered platform capable of distinguishing various biomarkers for cancer type identification and autonomous responsive therapeutics is urgently needed. Herein, a “one stop” production line with logic gated composite for tumor cell identification, related biomarker imaging, and subsequent gene therapy is proposed. The designed composite can specifically target cancer cells through incorporated aptamers, which endows it with identification preference for cancer cells with overexpressed membrane protein receptors. Internalized materials collapse in the acidic lysosome milieu, releasing the functioning DNA strands. Endogenous miR‐210 then can initiate cascade reactions with released strands, resulting in the liberation of therapeutic antisense oligonucleotides (ASO). The strategy is to construct a platform for cancer therapy based on second‐order AND Boolean logic operation for multiple cancer biomarkers (Mucin 1 (MUC1), Protein tyrosine kinase 7 (PTK7), and miR‐210) identification and succeeding therapy toward identified cells. Through the logic operation, produced fluorescent signals can disclose the types of biomarkers being recognized, while nano‐material endocytosis, subsequent miRNA imaging, and endogenous miRNA‐triggered gene therapy can all be performed concurrently. This “one stop” multifunctional production line demonstrates excellent sensitivity and accuracy, and presents promising prospects in the early diagnosis of tumors and precision medicine.
Abstract Herein, a stepwise central‐coordination strategy to engineer corrole‐based electrochemiluminescence (ECL), achieving enhanced ECL with low triggering potentials and efficient emission in aqueous media, is reported. Aluminum insertion and axial … Abstract Herein, a stepwise central‐coordination strategy to engineer corrole‐based electrochemiluminescence (ECL), achieving enhanced ECL with low triggering potentials and efficient emission in aqueous media, is reported. Aluminum insertion and axial pyridine coordination of free‐base meso ‐tris(pentafluorophenyl)corrole ( TPFC ) generate mono‐pyridine Al(III) TPFC ( Al‐TPFC ), which exhibits improved redox reversibility, reduced oxidation potentials, and a 24‐fold ECL enhancement with dual‐peak emission. Controlled conversion to bis‐pyridine Al(III) TPFC ( Al‐TPFC‐PY ) enables emission redshift and intensity modulation. Theoretical calculations identify ligand‐based locally excited states as the emission origin, emphasizing the crucial role of Al(III) in luminescence enhancement. Bovine serum albumin‐functionalized Al‐TPFC nanoparticles exhibit over 40‐fold higher ECL intensity in aqueous solution compared to TPFC nanoparticles, with further improvement achieved through tetraphenylethylene incorporation to suppress π–π stacking. This study establishes a coordination‐modulated ECL platform using ring‐contracted porphyrins, advancing both fundamental understanding and practical applications of ECL in functional π‐systems.
Hydrophobic interactions are one of the fundamental driving forces of self‐assembly in living systems. It remains challenging to harness hydrophobicity to have a controllable and programmable assembly of DNA nanostructures. … Hydrophobic interactions are one of the fundamental driving forces of self‐assembly in living systems. It remains challenging to harness hydrophobicity to have a controllable and programmable assembly of DNA nanostructures. On the other hand, there is also a need to explore orthogonal hierarchical assembly strategies to be used as an additional toolset along with the traditional Watson‐Crick base pairing to achieve complex superstructures. In this work, we rationally design and synthesize a series of low molecular weight hydrophobic molecules that are conjugated to single‐stranded DNA strands. By incorporating these modified DNA strands into the precisely defined locations of DNA tiles and origami nanostructures, we achieve controlled hierarchical assembly driven by hydrophobic interaction. We demonstrate a versatile hydrophobicity‐guided higher‐order assembly strategy by employing strategically engineered DNA nanostructures of increasing complexity, ranging from simple DNA tiles to complex origami structures, functionalized with these small hydrophobic molecules as programmable building blocks.
Hydrophobic interactions are one of the fundamental driving forces of self-assembly in living systems. It remains challenging to harness hydrophobicity to have a controllable and programmable assembly of DNA nanostructures. … Hydrophobic interactions are one of the fundamental driving forces of self-assembly in living systems. It remains challenging to harness hydrophobicity to have a controllable and programmable assembly of DNA nanostructures. On the other hand, there is also a need to explore orthogonal hierarchical assembly strategies to be used as an additional toolset along with the traditional Watson-Crick base pairing to achieve complex superstructures. In this work, we rationally design and synthesize a series of low molecular weight hydrophobic molecules that are conjugated to single-stranded DNA strands. By incorporating these modified DNA strands into the precisely defined locations of DNA tiles and origami nanostructures, we achieve controlled hierarchical assembly driven by hydrophobic interaction. We demonstrate a versatile hydrophobicity-guided higher-order assembly strategy by employing strategically engineered DNA nanostructures of increasing complexity, ranging from simple DNA tiles to complex origami structures, functionalized with these small hydrophobic molecules as programmable building blocks.
The rising global prevalence of Alzheimer's disease (AD) has emerged as a critical public health challenge, placing strain on families, communities, and healthcare systems. Despite advances in diagnostic methods, current … The rising global prevalence of Alzheimer's disease (AD) has emerged as a critical public health challenge, placing strain on families, communities, and healthcare systems. Despite advances in diagnostic methods, current techniques for early AD detection remain limited, often being invasive, costly, and impractical for regular use. Here, we report a fully integrated wearable nanosensor offering an easily accessible and user-friendly strategy for AD screening. This biosensing platform incorporates a microneedle-based interstitial fluid (ISF) sampling device and an ultrasensitive graphene field-effect transistor (GFET) chip, enabling rapid and precise detection of AD biomarkers. Furthermore, this nanosensor was successfully validated in transgenic murine models, demonstrating reliable differentiation between AD and non-AD mouse groups with high specificity. Overall, this study offers a promising alternative tool to the existing invasive and expensive techniques for the AD preliminary screening, paving the way for drug discovery, early diagnosis, and personalized treatment of AD.
Single-atom catalysts (SACs) have garnered significant attention as coreactant accelerators in luminol-dissolved O2 electrochemiluminescence (ECL) systems, but designing and fabricating highly efficient SACs remain a critical challenge. In this study, … Single-atom catalysts (SACs) have garnered significant attention as coreactant accelerators in luminol-dissolved O2 electrochemiluminescence (ECL) systems, but designing and fabricating highly efficient SACs remain a critical challenge. In this study, we present the first attempt to develop a high-entropy single-atom catalyst (HE-SAC) by rationally and atomically modulating multiple isolated heteroatom active sites (Fe, Co, Cu, Ni, and Mn) in M-N4 coordination moieties within pyridinic and pyrrolic nitrogen-rich graphitic frameworks. This HE-SAC features a square-planar geometric structure with low symmetry and a highly localized electron distribution, leading to enhanced catalytic activity for reactive oxygen species (ROS) generation and, consequently, improved luminol ECL performance. Synchrotron radiation analysis and density functional theory (DFT) calculations indicate that Mn-N4 and Co-N4 function as electron delocalizers to modulate the catalytic activity of Fe sites during O2 activation, while Ni-N4 and Cu-N4 promote weak binding with intermediates. The unique electronic structure and synergistic interaction among the HE-SAC metal active sites enhance the catalytic activity, boosting ROS production. The interactions between active sites and the graphenic support leverage high entropy to further boost the HE-SAC durability and catalytic efficiency. Furthermore, the incorporation of luminol-modified AgNPs with HE-SAC significantly enhances the ECL signal, resulting in a 5.9-fold increase compared with single Fe-SAC under optimal conditions, strongly aligning with theoretical DFT prediction. As a proof of concept, the acquired ECL biosensor was fruitfully applied to the ultrasensitive detection of miRNA-21. The regulation of high-entropy single heteroatoms offers a pioneering approach to accelerate intermediate generation for boosting coreactant ECL systems.
Abstract To increase the sensitivity of the graphene Field effect transistor (GFET) for viral detection, an acetate buffer at pH 4 was used instead of the conventional phosphate-buffer saline (PBS) … Abstract To increase the sensitivity of the graphene Field effect transistor (GFET) for viral detection, an acetate buffer at pH 4 was used instead of the conventional phosphate-buffer saline (PBS) at pH 7. We hypothesize that SARS-CoV-2 carries more positive charges in the acetate buffer, as its pH is further from the isoelectric point (pI) of SARS-CoV-2 (pI 5.2-6.0) compared to that of PBS. Additionally, GFET measurement results with and without poly-L-lysine (PLL) modification were compared. The dependence of sensitivity on the surface charge of graphene was estimated by solving the Poisson–Boltzmann equation, and the effect of PLL
modification on this dependence was discussed.
Abstract An increasing prevalence of illicit drugs, mainly date rape substances such as alprazolam, ketamine, GHB, LSD, and diazepam presents a growing threat to general safety. Rapid and accurate portable … Abstract An increasing prevalence of illicit drugs, mainly date rape substances such as alprazolam, ketamine, GHB, LSD, and diazepam presents a growing threat to general safety. Rapid and accurate portable detection technologies are thus much desired for effective monitoring and intervention. This review presents the latest updates on nanosensor detection platforms for the determination of these substances in several liquid media, including water, alcoholic beverages, and soft drinks. The employment of different advanced nanomaterials, gold nanoparticles, carbon nanotubes, and quantum dots, has greatly enhanced signal transduction, sensitivity, and selectivity of various sensing mechanisms, such as electrochemical, surface plasmon resonance, and fluorescence-based methods. A bibliometric study mapping worldwide trends in the subject field, key contributing areas, and publication outlets is given as an aid to the technical backdrop. Altogether, this intertwining view situates the development of science and simultaneously highlights emerging fields of interest and interdisciplinary couplings. Concerning the drawbacks of conventional methods, the review forwards a multipath sensing approach that makes use of synergistic properties of nanomaterials to engineer sensitive, inexpensive, and field-deployable detection devices. The presented outcomes stress the utmost importance of nanotechnology for future applications in drug detection, whose implications are on.
The environmental contamination caused by deoxynivalenol (DON) has become an emerging public health issue, and its sensitive and accurate analysis is crucial as its trace amounts and microchange in environmental … The environmental contamination caused by deoxynivalenol (DON) has become an emerging public health issue, and its sensitive and accurate analysis is crucial as its trace amounts and microchange in environmental monitoring and management. Here, piperazine-functionalized carbon dot aggregates (P-CDAs) with obvious aggregation-induced electrochemiluminescence (AIECL) properties strengthened by solvent regulation were synthesized, based on which an ECL aptasensor was constructed for the efficient detection of DON. In addition to the surface states optimizing originated from piperazine modification, the aggregation of the P-CDs was further facilitated through solvent regulation, which could directly influence the aggregated process and final ECL performance but was usually neglected in the precious AIECL study. Thus, selecting specific solvents and proportion control was very important for the AIECL. It showed that the P-CDAs could be excited more easily because of the reduced band gap energy and exhibited an improved and red-shifted ECL signal wavelength (603 nm) in ethanol/water (9:1 volume ratio). In addition, to achieve ultrasensitive detection of low-abundance DON, a DNA zipper structure-mediated localized hybridization chain reaction (Z-L-HCR) induced dual-output strategy was constructed. The proposed Z-L-HCR minimized the free diffusion of hairpin DNA, thereby enhancing the reaction rate. Simultaneously, both Z-L-HCR and dual-output mode reduced background signals effectively, realizing the ultrasensitive detection of DON with a detection limit of 0.112 fg/mL. In summary, surface modification and solvent regulation hold significant potential for enhancing the AIECL performance of carbon dots, and the proposed ECL aptasensor provides a reliable detection method for environmental monitoring and food safety.
Magnesium ions (Mg2+) play an important role in animal health, with their concentration in the bloodstream serving as a key indicator for hypomagnesemia diagnosis. In this study, a flexible hydrophobic … Magnesium ions (Mg2+) play an important role in animal health, with their concentration in the bloodstream serving as a key indicator for hypomagnesemia diagnosis. In this study, a flexible hydrophobic paper-based microfluidic field-effect biosensor was developed for point-of-care Mg2+ detection, which integrated flexible hydrophobic paper, semiconducting single-walled carbon nanotubes (SWNTs) and a Mg2+-specific RNA-cleaving DNAzyme(RCD)-based DNA nanostructure. Flexible hydrophobic paper was synthesized by using cellulose paper and octadecyltrichlorosilane, improving mechanical strength and decreasing biological interference. To achieve high sensitivity, the Mg2+-specific RCD was functionalized with SWNTs, and then repeatedly self-assembled two different Y-shaped DNAs to construct a DNA nanostructure based on a similar DNA origami technique. This proposed biosensor exhibited a linear detection range from 1 μM to 1000 μM, with a detection limit of 0.57 μM, demonstrating its great stability, selectivity, and anti-interference performance. This innovative design offers promising potential for Mg2+ monitoring in real applications.
Immunochromatographic assay (ICA) has been extensively utilized for on-site detection to ensure food safety. However, maintaining the bioactivity of immunoprobes while achieving efficient antibody labeling remains a significant challenge. In … Immunochromatographic assay (ICA) has been extensively utilized for on-site detection to ensure food safety. However, maintaining the bioactivity of immunoprobes while achieving efficient antibody labeling remains a significant challenge. In this study, a novel immunoprobe was developed by integrating tetrahedral DNA nanostructure (TDN) with protein A (PrA) and was subsequently applied in an ICA for the detection of lead ions. Notably, TDN served as a scaffold to enable a tailorable distribution of antibodies, while PrA acted as a bridging ligand to facilitate the oriented immobilization of antibodies. This strategy significantly enhanced the coupling efficiency of antibodies while maintaining their bioactivity. As expected, the proposed immunoprobe exhibited a higher affinity and a greater proportion of active antibodies compared to immunoprobes based solely on PrA or TDN. Moreover, the developed ICA achieved a visual limit of detection (vLOD) of 0.05 ng/mL and a scanning limit of quantitation (sLOQ) of 0.031 ng/mL for lead ions, respectively. By combining TDN and PrA, the AuNP-TDN-PrA-mAb immunoprobe enabled a controllable orientation and adjustable coverage density of antibodies. This unique property holds great potential for establishing a highly sensitive ICA, thereby meeting diverse detection requirements in practical applications.
The robustness and sensitivity of nucleic acid amplification (NAA)-integrated aptasensors for the detection of small molecules are currently challenged by the strict enzymatic conditions and low efficiency of strand displacement. … The robustness and sensitivity of nucleic acid amplification (NAA)-integrated aptasensors for the detection of small molecules are currently challenged by the strict enzymatic conditions and low efficiency of strand displacement. Herein, we proposed, for the first time, a small-molecule binding-guided NAA and accordingly developed a split aptamer ligation chain reaction (SPA-LCR) by a newly split aptamer and a copper-free click chemistry reaction. In the study, magnetic microbeads were employed as both DNA collectors and dispersed microelectrodes, and a SPA-LCR Mag-E-senor was constructed for a sensitive and specific detection of aflatoxin B1 (AFB1). The proposed method demonstrated a satisfactory performance for AFB1 detection, with a wide linear range from 0.1 to 1.0 × 103 ng/mL, a low detection limit of 16.7 pg/mL, and a high specificity toward one group discrimination. It also successfully detected the target of interest in complex matrices. This study provides a novel alternative for connecting small molecules with NAA and for small molecule biosensing, which is free of enzymatic restrictions and the elaborate design of strand displacement.
This work presents the theoretical design and optimization of a surface plasmon resonance (SPR) biosensor incorporating graphene, silicon nitride, and a thiol-tethered ssDNA layer for malaria detection and stage differentiation. … This work presents the theoretical design and optimization of a surface plasmon resonance (SPR) biosensor incorporating graphene, silicon nitride, and a thiol-tethered ssDNA layer for malaria detection and stage differentiation. Two configurations (Sys 3 and Sys 4 ) were simulated using the transfer matrix method to determine optimal material thicknesses. The final designs were evaluated against three malaria stages—ring, trophozoite, and schizont—based on their refractive index variations. Sys 3 achieved sensitivities of 353.14, 291.14, and 263.26°/RIU, while Sys 4 reached 315.71, 294.81, and 268.65°/RIU, respectively. These values exceed those reported in comparable SPR platforms. Sys 3 showed enhanced optical performance with a higher quality factor and lower detection limit, whereas Sys 4 offered improved biomolecular recognition. Although limited to simulation, the proposed configurations demonstrate potential for label-free, stage-specific malaria diagnostics, supporting future development toward point-of-care applications.
Abstract Chemiluminescent immunoassay is the most widely used protein detection technique in clinical diagnosis but still faces substantial challenges in antibody‐related single‐cell analysis due to the lack of a homogeneous … Abstract Chemiluminescent immunoassay is the most widely used protein detection technique in clinical diagnosis but still faces substantial challenges in antibody‐related single‐cell analysis due to the lack of a homogeneous immunoassay with strong and stable chemiluminescence signal. Herein, a single‐cell microfluidic platform for efficient in situ detection of antibody secreted from single hybridoma cells through a microcavity chemiluminescent immunoimaging (MCCLII) protocol is reported, which consist of an imidazole‐enhanced chemiluminescence system, a proximity‐triggered DNA nanomachine and a hybrid‐regulated hemin‐DNA switch. In MCCLII, antibody secreted from single hybridoma cells can be visualized through a homogeneous proximity CL assay, which converses the target antibody to DNA for triggering the DNA nanomachine and then activates the catalytic activity of hemin‐DNA switch to produce strong and persistent chemiluminescence for micro‐imaging. The MCCLII realizes immunoimaging detection down to 66 antibody molecules in 0.79‐nL microchamber and demonstrates the possibility of specific hybridoma cell screening within 30 min, which provides a simple and fast antibody screening platform to promote antibody‐drug production.
The development of dual-recognition and multisignal transduction sensing strategies is critical for achieving precise identification and ultrasensitive detection of small molecule contaminants. In this work, a fluorescence-photoelectrochemical (FL-PEC) "dual-signal on" … The development of dual-recognition and multisignal transduction sensing strategies is critical for achieving precise identification and ultrasensitive detection of small molecule contaminants. In this work, a fluorescence-photoelectrochemical (FL-PEC) "dual-signal on" sensing platform was presented based on a dual-recognition strategy combining molecularly imprinted polymers (MIPs) and aptamers. Specifically, the MIPs functionalized on the fluorescent carbon dots (CDs) (CDs@MIPs) served as the first recognition element, capturing target molecules and suppressing the photoinduced electron transfer (PET) effect, thereby triggering the fluorescence signal recovery (FL signal). The second recognition units consisted of target-specific aptamer-functionalized liposomes loaded with potassium ferricyanide (Apt@Lip-K3[Fe(CN)6]), quantitatively binding to the CDs@MIPs/target complex. Subsequent liposome lysis releases K3[Fe(CN)6], which acted as an electron acceptor to boost the photocurrent of CTAB@MAPbI3/ITO, generating a second photoelectrochemical signal increase (PEC signal). Using dibutyl phthalate (DBP) as a model contaminant, the dual-signal platform realized sensitive detection in the linear range of 0.1 nM-10.0 μM (FL) and 1.0 pM-0.1 μM (PEC), with detection limits of 71.30 pM (FL) and 0.648 pM (PEC) (S/N = 3), respectively. The MIPs-aptamer cooperative dual-recognition mechanism enabled complementary FL (rapid visual screening) and PEC (precise quantification) responses, ensuring cross-validated detection that minimizes false positives while enhancing sensitivity. The platform has also been applied for bisphenol A (BPA), another small molecule phenolic pollutant, showing its wide applicability as a universal platform for the detection of small molecule contaminants in food and environmental monitoring applications.
Surface plasmon resonance (SPR) detection technology is playing an important role in various fields such as food safety and environmental monitoring due to its excellent stability and reliability. However, there … Surface plasmon resonance (SPR) detection technology is playing an important role in various fields such as food safety and environmental monitoring due to its excellent stability and reliability. However, there is also a growing demand for higher sensitivity in SPR sensors. Therefore, this work developed an SPR sensor based on the synergistic effect of electric-field enhancement and adsorption enhancement by using amino acid-derived carbon dots (CDs). The results showed that the incorporation of amino acid CDs can generate a maximum electric-field enhancement of up to 6.44 × 105 V/m in the near-field region, which is 312% of that achieved by a bare gold film. And the adsorption kinetics results indicate that the active groups on the surface of amino acid CDs exhibit a notable adsorption enhancement effect for the target molecule (NaCl), with an adsorption capacity 335% higher than that of the bare gold film. This designed SPR sensor demonstrates a detection sensitivity of 167.28 a.u./RIU for NaCl solution, representing a 247.8% improvement compared to an SPR sensor without amino acid CDs under the same conditions. This SPR sensor shows promising potential for applications in biomedical and environmental detection fields.
Hyperspectral fluorescence imaging (HSFI) could simultaneously offer morphological visualization and microenvironmental information through fluorescence wavelength-shifting of microenvironmental-sensitive fluorescent probes, yet its advancement is directly hindered by the scarcity of probes … Hyperspectral fluorescence imaging (HSFI) could simultaneously offer morphological visualization and microenvironmental information through fluorescence wavelength-shifting of microenvironmental-sensitive fluorescent probes, yet its advancement is directly hindered by the scarcity of probes with sufficient spectral sensitivity. Herein, this study focuses on the development of an innovative fluorescent probe that exhibits heightened spectral sensitivity to microenvironmental changes and its advanced HSFI application. First, the comprehensive investigation of various donor-π-acceptor molecules uncovers the critical role of π-spacer on the wavelength sensitivity to microenvironment polarity. Based on this insight, a new fluorescent probe Lipi-PS of whose wavelength sensitivity represents the highest level so far is rationally developed. Further combining with the features of lipid droplets (LDs) targeting and high photostability of Lipi-PS, as well as the newly established wavelength and polarity encoding method, HSFI is successfully realized in cells, tissues, and zebrafishes. Accordingly, the structural morphologies, fluorescence wavelengths, and polarities are intuitively visualized in the HSFI images. Notably, a special HSFI of single LD is achieved using Lipi-PS in a custom-built 3D-SpecDIM system, allowing 5D tracking (xyzλt) of individual LDs for the first time. This enables unprecedented correlation of polarity-dynamic behavior at the single-LD level.
Background: Early detection of oncological diseases such as pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer (OV) is pivotal for successful treatment but remains a significant challenge due to the lack … Background: Early detection of oncological diseases such as pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer (OV) is pivotal for successful treatment but remains a significant challenge due to the lack of sensitive and specific diagnostic tests. Fluorescence spectroscopy, enhanced by the interaction of serum proteins with nanoparticles (NPs) based on linear-dendritic block copolymers, has emerged as a promising technique for the noninvasive detection of these malignancies. This study introduces a novel array-based assay methodology to evaluate the diagnostic capabilities of various NPs within serum samples using fluorescence. Methods: We synthesized three types of NPs (1-SH, 2-OH, 3-NH3+) and analyzed their fluorescence spectra in serum samples from patients with PDAC, OV, and control subjects. The samples were excited at 330 and 350 nm wavelengths to obtain their fluorescence emission spectra. An array of machine learning algorithms was applied, including boosting and tree-based methods, to assess the ability of the spectral data to discriminate between pathological and nonpathological states. The algorithms' performance was measured by the area under the receiver operating characteristic curves (AUC). Results: The fluorescence spectra revealed distinct patterns for PDAC and OV pathologies. 3-NH3+ NPs exhibited the highest differential capacity with AUCs exceeding 80% for PDAC across all algorithms, except one. 2-OH NPs showed a strong discriminatory ability for OV with AUCs over 70%, utilizing all but one of the algorithms. 1-SH NPs, however, did not significantly increase differentiability. Boosting algorithms generally outperformed other methods, indicating their suitability for this diagnostic approach. Conclusions: The proposed assay array methodology enables the systematic evaluation of NPs' diagnostic potential using fluorescence spectroscopy. The differential interactions between NPs and serum proteins specific to PDAC and OV highlight the method's capability to discern pathological states. These findings suggest a path forward for developing NP-assisted fluorescence spectroscopy as a viable tool for cancer diagnostics, potentially leading to earlier detection and improved patient outcomes.
Despite the indisputable efficacy of chemotherapy in the treatment of cancer, the adjustment of chemotherapy drug dosage remains a concern. Therefore, herein, a flower‐like nanomaterial is developed as an electrochemical … Despite the indisputable efficacy of chemotherapy in the treatment of cancer, the adjustment of chemotherapy drug dosage remains a concern. Therefore, herein, a flower‐like nanomaterial is developed as an electrochemical nanobiosensor for cancer drug determination, considering the advantages of providing a lower limit of detection (LOD) by increasing the electrode surface area. A flower‐like porous manganese oxide (MnO 2 ) is synthesized and modified onto the surface of a pencil graphite electrode (PGE). It is used to investigate the interaction between dsDNA and daunorubicin (DNR), as an anticancer drug, using the voltammetric technique. As a result of the measurements made with developed MnO 2 ‐PGE using DPV, the LODs of dsDNA and DNR are calculated as 0.62 μg mL −1 and 54 nM, respectively. The dsDNA–DNR interaction investigation revealed that, in just three minutes, the maximum interaction is achieved and a 26.9% reduction in the dsDNA guanine signal is noted. On the other hand, there is an 81.2% decrease in the DNR oxidation signal. Kinetic investigation shows a binding constant ( K ) of 1.81 × 10 6 M −1 between dsDNA and DNR. The LOD of DNR using the dsDNA/MnO 2 ‐PGE surface is calculated as 0.06 μM in a linear dynamic range of 0.1–0.5 μM.
Abstract Monoclonal antibodies demonstrate significant potential in the clinical management of Human Epidermal Growth Factor Receptor 2/Estrogen Receptor‐positive (HER2/ER+) breast cancer. However, the therapeutic outcomes of antitumor drugs are significantly … Abstract Monoclonal antibodies demonstrate significant potential in the clinical management of Human Epidermal Growth Factor Receptor 2/Estrogen Receptor‐positive (HER2/ER+) breast cancer. However, the therapeutic outcomes of antitumor drugs are significantly hampered by challenges such as inter‐pathway crosstalk, the restricted efficacy of single‐pathway mechanisms, and suboptimal drug targeting. Herein, this study developed a Zr/Fe bimetallic MOF loaded with Cyclin‐dependent kinases 4 and 6 (CDK4/6) inhibitor ribociclib and surface‐functionalized with trastuzumab (Herceptin). Under the acidic tumor microenvironment (TME), this nanomaterial degrades, releasing trastuzumab, ribociclib, and Fe³⁺. Trastuzumab enhances tumor targeting, reduces normal tissue toxicity, and inhibits Cyclin D1‐CDK4/6 activation to decrease retinoblastoma (RB) phosphorylation, while ribociclib suppresses CDK4/6 enzymatic activity, synergistically blocking RB phosphorylation, inducing G1‐phase arrest, and halting tumor proliferation. Additionally, Fe³⁺ catalyzes the conversion of H₂O₂ into highly cytotoxic hydroxyl radicals (·OH) through the Fenton reaction, leading to oxidative stress‐induced cellular damage. Together, these three components synergistically inhibit the proliferation of HER2/ER+ breast cancer cells by disrupting cell cycle progression and cellular homeostasis. In vivo studies demonstrated that Zr‐Fe MOF@Ribociclib@Herceptin (ZFRH) not only significantly inhibits the growth of orthotopic tumors but also effectively suppresses the formation of lung‐metastatic tumors. These findings suggest a promising strategy for the precision‐targeted therapy of HER2/ER+ breast cancer.
The concept of utilizing synthetic nucleic acids and their conjugates with biologically active molecules as RNA-targeted therapeutic agents represents a powerful strategy in the treatment of human pathologies. Recent research … The concept of utilizing synthetic nucleic acids and their conjugates with biologically active molecules as RNA-targeted therapeutic agents represents a powerful strategy in the treatment of human pathologies. Recent research demonstrates that neoplastic development is closely associated with dysregulation of miRNAs, which are essential regulators of gene expression, highlighting the potential of therapeutic strategies aimed at their inhibition. Current approaches to pathological microRNA (miRNA) regulation primarily rely on physical blocking or sequestration mechanisms. However, these non-enzymatic strategies are limited by their stoichiometric nature, necessitating high drug doses to achieve therapeutic efficacy. A promising alternative lies in the application of catalytic nucleic acids, including miRNA-targeted ribozymes, DNAzymes/XNAzymes (antimiRzymes), and artificial ribonucleases (miRNases), which enable selective suppression of overexpressed miRNAs in pathological conditions through multiple enzymatic cleavage events. This review examines the fundamental principles governing the design of currently developed antimiRzymes and miRNases, analyzes their ribonuclease activity using synthetic miRNA substrates, and discusses key achievements in miRNA-inhibiting capability in tumor cells, along with their antitumor effects. Being effective RNA cleavers, these catalytic nucleic acids demonstrate remarkable potential, often surpassing the efficacy of conventional antisense oligonucleotides, and represent a promising therapeutic modality for RNA-associated diseases.
Cancer remains a leading cause of morbidity and mortality worldwide. The timely and accurate detection of potential early cancer biomarkers is essential for early cancer diagnosis. In recent years, electrochemical … Cancer remains a leading cause of morbidity and mortality worldwide. The timely and accurate detection of potential early cancer biomarkers is essential for early cancer diagnosis. In recent years, electrochemical biosensors have garnered significant attention due to their portability, cost-effectiveness, and ease of use. In addition, given their exceptional physicochemical properties, functional nanomaterials have found extensive applications in the field of electrochemical biosensing. This review provides an overview of the basic principles and types of electrochemical biosensors, the classification and properties of functional nanomaterials, and the application of functional nanomaterial-based electrochemical biosensors in the detection of cancer biomarkers. Finally, the prospects and remaining challenges of functional nanomaterial-based electrochemical biosensors in cancer diagnosis are discussed.
In this study, a multifunctional tetrahedral DNA nanostructure (MTDN) was constructed by assembling different functional modules for the simultaneous sensitive detection and imaging of targets miRNA-21 and Zn2+ in living … In this study, a multifunctional tetrahedral DNA nanostructure (MTDN) was constructed by assembling different functional modules for the simultaneous sensitive detection and imaging of targets miRNA-21 and Zn2+ in living cells related to liver cancer. Impressively, compared with the traditional detection strategy for miRNA-21 and Zn2+ with low sensitivity, this strategy employs autocatalytic hairpin assembly (ACHA) to rapidly self-assemble into linear tetrahedral DNA nanostructures (LTDNS) by activating the functional module on MTDN to produce two strong fluorescent signals for sensitive detection of miRNA-21 and Zn2+ with detection limits of 0.79 pM and 33.46 nM, respectively, which were much lower than the reported literature. More importantly, LTDNS with a spatial confinement effect and low diffusion coefficient could achieve accurate localization imaging of targets to significantly enhance imaging clarity. The strategy provides an innovative method for simultaneous sensitive detection and accurate imaging of multiple biomarkers and has broad application prospects in early disease diagnosis.
Salmonella enterica can penetrate inside eggshells through horizontal transmission; thus, a rapid detection method on this matrix is needed. This study aimed to develop an electrochemical nanobiosensor prototype based on … Salmonella enterica can penetrate inside eggshells through horizontal transmission; thus, a rapid detection method on this matrix is needed. This study aimed to develop an electrochemical nanobiosensor prototype based on the hyperinvasive locus A (hilA) gene of Salmonella enterica for rapid (< 8 hrs) detection of the foodborne pathogen in this matrix. The biosensor was characterized in terms of sensitivity, selectivity and linear detection range as well as its capability to rapidly detect artificially spiked S. enterica in chicken eggshells. The presence of the target hilA gene was also validated through PCR. The hilA genosensor had a linear detection range of 0.30 – 30 ng/µL or 6.84 – 684.5 nM with R2 = 0.8647 at p<0.01 as well as having sensitivity as low as 0.3 ng/µL or 6.84 nM. The nanobiosensor is specific to S. enterica with significantly higher current responses for S. enterica subsp. enterica serotype Enteritidis (6.13±0.69 µA) and S. enterica subsp. enterica serotype Typhimurium (3.59±0.26 µA) as compared with Shigella spp. (1.08±0.23 µA), E. coli O157:H7 (0.88±0.58 µA) and blank (0.67±0.08 µA). Artificially spiked S. enterica serovar Enteritidis (8×104 CFU/mL) in chicken eggshell samples were successfully detected, without DNA amplification, with peak current response of 4.69±1.38 µA against the blank (0.47±0.18 µA). With rapid analysis time (1.5 hrs target hybridization and detection excluding sample processing and 2.5 hrs offline screen-printed carbon electrode preparation), preliminary results show that the developed nanobiosensor could be used to monitor eggs for horizontal Salmonella contamination and improve food safety monitoring in layer farms.
Abstract Single‐molecule immunoassay is a reliable technique for the detection and quantification of low‐abundance blood biomarkers, which are essential for early disease diagnosis and biomedical research. However, current single‐molecule methods … Abstract Single‐molecule immunoassay is a reliable technique for the detection and quantification of low‐abundance blood biomarkers, which are essential for early disease diagnosis and biomedical research. However, current single‐molecule methods predominantly rely on endpoint detection and necessitate signal amplification via labeling, which brings a variety of unwanted effects, like matrix effect and autofluorescence interference. This study introduces a real‐time mass imaging‐based label‐free single‐molecule immunoassay (LFSMiA). Featuring plasmonic scattering microscopy‐based mass imaging, a 2‐step sandwich assay format enables background reduction, minimization of matrix effect by dynamic tracking of single binding events, and fully leveraging real‐time data for improved measurement precision through a Bayesian Gaussian process model, the LFSMiA enables ultra‐sensitive and direct protein detection at the single‐molecule level in neat blood sample matrices. LFSMiA measurement is demonstrated for interleukin‐6 and prostate‐specific antigen in buffer, undiluted serum, and whole blood with sub‐femtomolar detection limits and eight logs of dynamic ranges. Moreover, comparable performance is achieved with an inexpensive miniaturized setup. To show its translational potential to clinical settings and point‐of‐care diagnostics, N‐terminal pro‐B‐type natriuretic peptide is examined in patient whole blood samples using the LFSMiA and results in a strong linear correlation (r > 0.99) with standard clinical lab results.
Abstract This study investigates the electronic properties of a proposed composite structure consisting of SiO 2 , Pb 3 O 4 , Bi 2 O 3 , and graphene oxide … Abstract This study investigates the electronic properties of a proposed composite structure consisting of SiO 2 , Pb 3 O 4 , Bi 2 O 3 , and graphene oxide (GO) for glutamic acid (Glu) biosensing applications in aqueous media. Using Density Functional Theory (DFT) at B3LYP functional and SDD basis set, we examine the reactivity and electronic properties of the combination of these structures under weak and complex interaction scenarios with Glu. The study focuses on studying total dipole moments (TDM), HOMO/LUMO bandgaps, molecular electrostatic potential (MEP) maps, reactivity descriptors, and the density of states (DOS) for the proposed model molecules. The calculated TDMs and HOMO/LUMO bandgap energies highlight the highly reactive nature of the 3SiO 2 /GO/Pb 3 O 4 /Bi 2 O 3 “complex” structure toward the surrounding species. This is because it has the highest TDM (up to 35.1 Debye) and the lowest bandgap energy (decline significantly to 0.158 eV). The MEP maps for the interaction between 3SiO 2 /GO/Pb 3 O 4 /Bi 2 O 3 and Glu under the two proposed scenarios display markedly different MEP profiles, underscoring the substantial impact of the interaction type. Additionally, the interaction between 3SiO 2 /GO/Pb 3 O 4 /Bi 2 O 3 “complex” structure and Glu exhibits the highest ionization potential, electron affinity, and electronegativity. The plotted DOS curves of the interaction between the proposed composite structure (both weak and complex forms) and the target analyte reveal that the unoccupied states begin to emerge slightly below − 4.0 eV and − 5.0 eV, then extend towards 0.0 eV, indicating potential excitation energies for electrons. These findings boost the potential of the proposed 3SiO 2 /GO/Pb 3 O 4 /Bi 2 O 3 structure as a promising candidate for tailoring novel electrode materials for Glu biosensing applications, thereby advancing the development of effective biosensors.