Piezoelectric microcantilever serum protein detector

The development of a serum protein detector will provide opportunities for better screening of at‐risk cancer patients, tighter surveillance of disease recurrence and better monitoring of treatment. An integrated system that can process clinical samples for a number of different types of biomarkers would be a useful tool in the early detection of cancer. Also, screening iomarkers such as antibodies in serum would provide clinicians with information regarding the patient’s response to treatment. Therefore, the goal of this study is to develop a sensor which can be used for rapid, all‐electrical, real‐time, label‐fee, in‐situ, specific quantification of cancer markers, e.g., human epidermal receptor 2 (Her2)or antibodies, in serum. To achieve this end, piezoelectric microcantilever sensors (PEMS) were constructed using an 8 μm thick lead magnesium niobate‐lead titanate (PMN‐PT) freestanding film as the piezoelectric layer. The desired limit of detection is on the order of pg/mL. In order to achieve this goal the higher frequency lateral extension modes were used. Also, as the driving and sensing of the PEMS is electrical, the PEMS must be insulated in a manner that allows it to function in aqueous solutions. The insulation layer must also be compatible with standardized bioconjugation techniques. Finally, detection of both cancer antigens and antibodies in serum was carried out, and the results were compared to a standard commercialized protocol. PEMS have demonstrated the capability of detecting Her2 at a concentration of 5 pg/mL in diluted human serum (1:40) in less than 1 hour. The approach can be easily translated into the clinical setting because the sensitivity is more than sufficient for monitoring prognosis of breast cancer patients. In addition to Her2 detection, antibodies in serum were assayed in order to demonstrate the feasibility of monitoring the immune response for antibody‐dependent cellular cytotoxicity (ADCC) in patients on antibody therapies such as Herceptin and Cetuximab. The PEMS displayed a limit of detection of 100 fg/mL, which was 100 times lower than the current methods of protein detection in serum, such as ELISA. Furthermore, the sensitivity of the PEMS device allows it to be capable of determining the dissociation constant, Kd, of selective receptors such as antibodies. Using the dose response trials of Her2, Kd has been deduced for H3 scFv, and Herceptin, a commercial antibody specific for Her2.Ph.D., Materials Engineering -- Drexel University, 200

Methyltrimethoxysilane-insulated piezoelectric microcantilevers for direct, all-electrical biodetection in buffered aqueous solutions

Review of Scientific Instruments, 77(12).We have examined coating PbMg1/3Nb2/3O3 0.63– PbTiO3 0.37 PMN-PT /tin piezoelectric microcantilever sensors PEMSs with a thin methyltrimethoxysilane MTMS by a simple solution method to electrically insulate the PEMS for biodetection in phosphate buffered saline PBS solutions. The PMN-PT/tin PEMSs were constructed using PMN-PT freestanding films that exhibited an electric-field-enhanced giant piezoelectric coefficient. The insulation procedure involved spin coatings of MTMS followed by cross-linking in water, which yielded a coating layer of about 10 nm in thickness on the tin side of the PEMS. We showed that the MTMS-insulated PMN-PT/tin PEMSs were capable of electrical self-excitation and self-sensing with a stable resonance spectrum exhibiting a quality factor of Q=50 when submerged in 0.1M PBS solution. Direct, all-electrical, in situ detection of Escherichia coli O157:H7 at various concentrations was demonstrated at a flow rate of 0.5 ml/min. A MTMS-insulated PMN-PT/tin PEMS 725 m long consisting of a 22- m-thick PMN-PT layer and a 6- m-thick tin layer exhibited a mass detection sensitivity m/ f =−3±2 10−12 g/Hz and a concentration sensitivity of better than 100 cells/ml in less than 1 ml of liquid

Design status of ASPIICS, an externally occulted coronagraph for PROBA-3

The "sonic region" of the Sun corona remains extremely difficult to observe with spatial resolution and sensitivity sufficient to understand the fine scale phenomena that govern the quiescent solar corona, as well as phenomena that lead to coronal mass ejections (CMEs), which influence space weather. Improvement on this front requires eclipse-like conditions over long observation times. The space-borne coronagraphs flown so far provided a continuous coverage of the external parts of the corona but their over-occulting system did not permit to analyse the part of the white-light corona where the main coronal mass is concentrated. The proposed PROBA-3 Coronagraph System, also known as ASPIICS (Association of Spacecraft for Polarimetric and Imaging Investigation of the Corona of the Sun), with its novel design, will be the first space coronagraph to cover the range of radial distances between ~1.08 and 3 solar radii where the magnetic field plays a crucial role in the coronal dynamics, thus providing continuous observational conditions very close to those during a total solar eclipse. PROBA-3 is first a mission devoted to the in-orbit demonstration of precise formation flying techniques and technologies for future European missions, which will fly ASPIICS as primary payload. The instrument is distributed over two satellites flying in formation (approx. 150m apart) to form a giant coronagraph capable of producing a nearly perfect eclipse allowing observing the sun corona closer to the rim than ever before. The coronagraph instrument is developed by a large European consortium including about 20 partners from 7 countries under the auspices of the European Space Agency. This paper is reviewing the recent improvements and design updates of the ASPIICS instrument as it is stepping into the detailed design phase

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Magnetic capture device for large volume sample analysis.

Immunomagnetic separation (IMS) techniques employing superparamagnetic particles can successfully isolate various components from mixtures. However, their utility can be limited for large-volume samples, viscous samples, or those containing a high density of particulate matter because of the need to generate high field gradients for particle recovery. Therefore, a new class of immunomagnetic particles was devised utilizing a single, macroscopic Pyrex spinbar conjugated with biorecognition elements to address these limitations. Advantages include an inherent capacity for effective mixing, an almost instantaneous recovery of the spinbar that can be performed without expensive equipment and with no loss of magnetic particles during processing, and reduced transfer of sample matrix. As a result, spinbars can provide an effective means for IMS with large-volume assays composed of complex matrices

Flow-Through Electrochemical Biosensor for the Detection of Listeria monocytogenes Using Oligonucleotides

Consumption of food contaminated by Listeria monocytogenes can result in Listeriosis, an illness with hospitalization rates of 94% and mortality rates up to 30%. As a result, U.S. regulatory agencies governing food safety retain zero-tolerance policies for L. monocytogenes. However, detection at such low concentrations often requires strategies such as increasing sample size or culture enrichment. A novel flow-through immunoelectrochemical biosensor has been developed for Escherichia coli O157:H7 detection in 1 L volumes without enrichment. The current work further augments this biosensor’s capabilities to (1) include detection of L. monocytogenes and (2) accommodate genetic detection to help overcome limitations based upon antibody availability and address specificity errors in phenotypic assays. Herein, the conjugation scheme for oligo attachment and the conditions necessary for genetic detection are laid forth while results of the present study demonstrate the sensor’s ability to distinguish L. monocytogenes DNA from L. innocua with a limit of detection of ~2 × 104 cells/mL, which agrees with prior studies. Total time for this assay can be constrained to <2.5 h because a timely culture enrichment period is not necessary. Furthermore, the electrochemical detection assay can be performed with hand-held electronics, allowing this platform to be adopted for near-line monitoring systems

Particle recovery.

Factors affecting particle recovery from stomached ground beef can include particulate settlement (left) as well as physical properties of both the magnetic particles and the matrix (right).</p

Cell capture via IMS using Pyrex spinbars and SPPs.

Assessment of E. coli cells captured by the anti-E. coli conjugated spinbars (blue bars) or anti-E. coli conjugated SPPs (red bars) from a 0.5 L ground beef slurry using qPCR. Non-inoculated ground beef samples (no cells), two inoculation levels of E. coli O157:H7 (10^5 and 10^6 cells), and spinbars/SPPs without antibodies (no Ab) in the presence of 10^6 E. coli O157:H7 cells were compared. Averages from 3 independent trials are shown with error bars representing the standard deviation of the mean. The grey line represents the Ct value obtained from E. coli without ground beef present for use as a positive control. Groups containing different letter designations were deemed significantly different (p≤ 0.05).</p

Immobilization of antibodies on spinbars.

Pyrex-coated spinbars both with anti-His antibodies conjugated to HRP (red) and without antibodies (blue) were tested for the presence of HRP via an enzymatic assay that results in the oxidation of TMB and production of a chromogenic product. The chromogenic product was measured via spectrophotometry at 450 nm. The positive control (striped, red bar) contained purified HRP-conjugated antibodies and the negative control (striped, blue bar) contained the TMB/H2O2 alone, with neither control containing a spinbar. Averages from 3 readings are shown with error bars representing the standard deviation of the mean. Groups containing different letter designations were deemed significantly different (p≤ 0.05).</p