Early and timely diagnosis of cancer plays a decisive role in appropriate treatment and improves clinical outcomes, improving public health. Significant advances in biosensor technologies are leading ...to the development of point-of-care (POC) diagnostics, making the testing process faster, easier, cost-effective, and suitable for on-site measurements. Moreover, the incorporation of various nanomaterials into the sensing platforms has yielded POC testing (POCT) platforms with enhanced sensitivity, cost-effectiveness and simplified detection schemes. POC cancer diagnostic devices provide promising platforms for cancer biomarker detection as compared to conventional in vitro diagnostics, which are time-consuming and require sophisticated instrumentation, centralized laboratories, and experienced operators. Current innovative approaches in POC technologies, including biosensors, smartphone interfaces, and lab-on-a-chip (LOC) devices are expected to quickly transform the healthcare landscape. However, only a few cancer POC devices (e.g. lateral flow platforms) have been translated from research laboratories to clinical care, likely due to challenges include sampling procedures, low levels of sensitivity and specificity in clinical samples, system integration and signal readout requirements. In this review, we emphasize recent advances in POC diagnostic devices for cancer biomarker detection and discuss the critical challenges which must be surmounted to facilitate their translation into clinical settings.
Display omitted
•Advances in the POC cancer devices, including paper, screen printed electrode, and smartphone-based platforms are discussed.•The application of nanomaterials in POC cancer detection devices are reviewed.•Commercially available POC cancer diagnostic devices are presented.•The key challenges of POC cancer devices and the future needs to facilitate their clinical translation are presented.
Field effect transistor (FET) based sensors have attractive features such as small size, ease of mass production, high versatility and comparably low costs. Over the last decade, many FET type ...biosensors based on various nanomaterials (e.g. silicon nanowires, graphene, and transition metal dichalcogenides) have been developed to detect various classes of biomolecular targets due to their integration into portable and rapid test systems, both for use in the clinical lab and in point-of-care testing. This review (with 197 refs.) starts with an introduction into the specific features of FET biosensor technology. This is followed by a description of the essentials of methods for immobilization of recognition elements. The next section discusses the progress that has been made in FET based biosensors using semiconducting nanostructures composed of silicon, graphene, metal oxides, and transition metal dichalcogenides. A further section is devoted to microfluidic systems combined with FET biosensors. We then emphasize the biosensing applications of these diagnostic devices for analysis of clinically relevant biomarkers, specifically to sensing of neurotransmitters, metabolites, nucleic acids, proteins, cancer and cardiac biomarkers. Two tables are presented which summarize advances in applications of 1D and 2D nanomaterial-based FETs for biomarker sensing. A concluding section summarizes the current status, addresses current challenges, and gives perspective trends for the field.
Graphical abstract
Field effect transistor devices based on the use of 1D and 2D semiconductor nanostructures (so called nano-FETs) are making use of materials including silicon nanowires, graphene, zinc oxide, indium oxide, titanium oxide, and molybdenum disulfide that are further modified with recognition elements for biosensing application.
We integrated the genomic sequencing of 1,918 breast cancers, including 1,501 hormone receptor-positive tumors, with detailed clinical information and treatment outcomes. In 692 tumors previously ...exposed to hormonal therapy, we identified an increased number of alterations in genes involved in the mitogen-activated protein kinase (MAPK) pathway and in the estrogen receptor transcriptional machinery. Activating ERBB2 mutations and NF1 loss-of-function mutations were more than twice as common in endocrine resistant tumors. Alterations in other MAPK pathway genes (EGFR, KRAS, among others) and estrogen receptor transcriptional regulators (MYC, CTCF, FOXA1, and TBX3) were also enriched. Altogether, these alterations were present in 22% of tumors, mutually exclusive with ESR1 mutations, and associated with a shorter duration of response to subsequent hormonal therapies.
Display omitted
•We performed prospective sequencing of 1,501 HR+ breast cancers in the clinical setting•MAPK and TF alterations were present in 22% of 692 HR+ post-endocrine therapy tumors•MAPK and TF alterations were mutually exclusive with ESR1 mutations•MAPK and TF alterations were associated with shorter response to endocrine therapies
Razavi et al. identify mutations in the MAPK pathway and the estrogen receptor transcriptional program in 22% of hormone receptor-positive breast cancers after hormone therapy. These mutations are mutually exclusive with ESR1 mutations and correlate with a shorter response duration to subsequent hormone therapies.
Display omitted
•The interaction of DNA, including DNA nanostructures, and graphene is reviewed.•Comparison of DNA graphene field-effect transistor (GFET) with other detection methods.•Discussion of ...challenges present in the detection mechanism of GFETs.•Use of DNA aptamer GFET sensors for the detection of small molecules and proteins.
Graphene field-effect transistors (GFET) have emerged as powerful detection platforms enabled by the advent of chemical vapor deposition (CVD) production of the unique atomically thin 2D material on a large scale. DNA aptamers, short target-specific oligonucleotides, are excellent sensor moieties for GFETs due to their strong affinity to graphene, relatively short chain-length, selectivity, and a high degree of analyte variability. However, the interaction between DNA and graphene is not fully understood, leading to questions about the structure of surface-bound DNA, including the morphology of DNA nanostructures and the nature of the electronic response seen from analyte binding. This review critically evaluates recent insights into the nature of the DNA graphene interaction and its affect on sensor viability for DNA, small molecules, and proteins with respect to previously established sensing methods. We first discuss the sorption of DNA to graphene to introduce the interactions and forces acting in DNA based GFET devices and how these forces can potentially affect the performance of increasingly popular DNA aptamers and even future DNA nanostructures as sensor substrates. Next, we discuss the novel use of GFETs to detect DNA and the underlying electronic phenomena that are typically used as benchmarks for characterizing the analyte response of these devices. Finally, we address the use of DNA aptamers to increase the selectivity of GFET sensors for small molecules and proteins and compare them with other, state of the art, detection methods.
DNA methylation, a stable and heritable covalent modification which mostly occurs in the context of a CpG dinucleotide, has great potential as a biomarker to detect disease, provide prognoses and ...predict therapeutic responses. It can be detected in a quantitative manner by many different approaches both genome-wide and at specific gene loci, in various biological fluids such as urine, plasma, and serum, which can be obtained without invasive procedures. The current, classical methods are effective in studying DNA methylation patterns, however, for the most part; they have major drawbacks such as expensive instruments, complicated and time consuming protocols as well as relatively low sensitivity, and high false positive rates. To overcome these obstacles, great efforts have been made toward the development of reliable sensor devices to solve these limitations, providing sensitive, fast and cost-effective measurements. The use of biosensors for DNA methylation biomarkers has increased in recent years, because they are portable, simple, rapid, and inexpensive which offers a straightforward way to detect methylated biomarkers. In this review, we give an overview of the conventional techniques for the detection of DNA methylation and then will focus on recent advances in biosensor based methylation detection that eliminate bisulfite conversion and PCR amplification.
DNA methylation, a stable and heritable covalent modification which mostly occurs in the context of a CpG dinucleotide, has great potential as a biomarker to detect disease, provide prognoses and predict therapeutic responses.
Significance This study is the first demonstration, to our knowledge, of the application of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) for discrimination of breast cancer ...and delineation of tumor margins. Using DESI-MSI, it is possible to discriminate between cancerous and adjacent normal tissue on the basis of the detection and specific spatial distributions of different lipid species. This study proves the feasibility of classifying cancerous and normal breast tissues using ambient ionization MSI. It will allow the surgeon to access to this information in real time so as to make accurate intraoperative decisions quickly. It will result in improved cosmesis and decrease the need for multiple operations for margin reexcision.
Distinguishing tumor from normal glandular breast tissue is an important step in breast-conserving surgery. Because this distinction can be challenging in the operative setting, up to 40% of patients require an additional operation when traditional approaches are used. Here, we present a proof-of-concept study to determine the feasibility of using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) for identifying and differentiating tumor from normal breast tissue. We show that tumor margins can be identified using the spatial distributions and varying intensities of different lipids. Several fatty acids, including oleic acid, were more abundant in the cancerous tissue than in normal tissues. The cancer margins delineated by the molecular images from DESI-MSI were consistent with those margins obtained from histological staining. Our findings prove the feasibility of classifying cancerous and normal breast tissues using ambient ionization MSI. The results suggest that an MS-based method could be developed for the rapid intraoperative detection of residual cancer tissue during breast-conserving surgery.
Development of a simple and efficient methodology to control the placement, spacing, and alignment of single-walled carbon nanotubes (SWCNTs) is essential for nanotechnology device application. ...Building on the growing understanding that the strong π–π interaction between the bases of single-stranded DNA (ssDNA) and CNTs is sufficient not only to drive CNT solubility in water but also to stabilize individual nanotubes against clustering in aqueous solution, a new motif for functionalizing DNA origami (DO) with CNTs is demonstrated. CNTs solubilized via wrapping with ssDNA react with DO constructs displaying linear arrays of ssDNA, leading to immobilization of the CNTs onto the DO scaffold. This study demonstrates the immobilization of ssDNA-wrapped CNTs at specific positions on single DO constructs. Furthermore, multiple DO constructs assembled into extended one-dimensional arrays have been used to successfully align pairs of CNTs exceeding 500 nm in length in a parallel orientation. This result provides a simplified, alternative approach to immobilization of CNTs with programmed spacing and orientation.
Precisely patterning proteins and other molecules at the nanoscale is crucial to future biosensing and optoelectronic applications. One- and two-dimensional DNA nanoconstructs have proven to be ...useful scaffolds for nanopatterning. This paper demonstrates the application of nitrilotriacetic acid (NTA) forming chelate complexes to localize histidine (His) tagged proteins via Ni2+ ions onto DNA based structures. Particularly, enhanced green fluorescent protein (EGFP) was directed to specific surface locations on a designed DNA Origami nanoconstruct, and the resulting EGFP nanopattern was visualized using atomic force microscopy (AFM).
The exploitation of DNA for the production of nanoscale architectures presents a young yet paradigm breaking approach, which addresses many of the barriers to the self-assembly of small molecules ...into highly-ordered nanostructures via construct addressability. There are two major methods to construct DNA nanostructures, and in the current review we will discuss the principles and some examples of applications of both the tile-based and DNA origami methods. The tile-based approach is an older method that provides a good tool to construct small and simple structures, usually with multiply repeated domains. In contrast, the origami method, at this time, would appear to be more appropriate for the construction of bigger, more sophisticated and exactly defined structures.
Tardigrades are renowned for their ability to survive a wide array of environmental stressors. In particular, tardigrades can curl in on themselves while losing a significant proportion of their ...internal water content to form a structure referred to as a tun. In surviving varying conditions, tardigrades undergo distinct morphological transformations that could indicate different mechanisms of stress sensing and tolerance specific to the stress condition. Methods to effectively distinguish between morphological transformations, including between tuns induced by different stress conditions, are lacking. Herein, an approach for discriminating between tardigrade morphological states is developed and utilized to compare sucrose- and CaCl2-induced tuns, using the model species Hypsibius exemplaris. A novel approach of shadow imaging with confocal laser scanning microscopy enabled production of three-dimensional renderings of Hys. exemplaris in various physiological states resulting in volume measurements. Combining these measurements with qualitative morphological analysis using scanning electron microscopy revealed that sucrose- and CaCl2-induced tuns have distinct morphologies, including differences in the amount of water expelled during tun formation. Further, varying the concentration of the applied stressor did not affect the amount of water lost, pointing towards water expulsion by Hys. exemplaris being a controlled process that is adapted to the specific stressors.
PDF
