A novel identification method for ultra trace detection of biomolecules using functionalised Surface Enhanced Raman Spectroscopy (SERS)

This thesis developed a new method for measuring extremely low amounts of organic and biological molecules, using Surface enhanced Raman Spectroscopy. This method has many potential applications, e.g. medical diagnosis, public health, food provenance, antidoping, forensics and homeland security. The method development used caffeine as the small molecule example, and erythropoietin (EPO) as the large molecule. This method is much more sensitive and specific than currently used methods; rapid, simple and cost effective. The method can be used to detect target molecules in beverages and biological fluids without the usual preparation steps.

Detection of object onset and offset in naturalistic scenes

The present study was conducted to investigate whether ob- servers are equally prone to overlook any kinds of visual events in change blindness. Capitalizing on the finding from visual search studies that abrupt appearance of an object effectively captures observers' attention, the onset of a new object and the offset of an existing object were contrasted regarding their detectability when they occurred in a naturalistic scene. In an experiment, participants viewed a series of photograph pairs in which layouts of seven or eight objects were depicted. One object either appeared in or disappeared from the layout, and participants tried to detect this change. Results showed that onsets were detected more quickly than offsets, while they were detected with equivalent ac- curacy. This suggests that the primacy of onset over offset is a robust phenomenon that likely makes onsets more resistant to change blindness under natural viewing conditions.

Nucleic acid hybridizations as radioactive tool for rapid detection of banana bunchy top virus

Banana bunchy top disease (BBTD) caused by banana bunchy top virus (BBTV) was radioactively detected by nucleic acid hybridization techniques. Results showed that, 32P-labelled insert of pBT338 was hybridized with nucleic acid extracts from BBTV-infected plants from Egypt and Australia but not with those from CMV-infected plants from Egypt. Results revealed that BBTV was greatly detected in midrib, roots, meristem, corm, leaves and pseudostem respectively. BBTV was also detected in symptomless young plants prepared from diseased plant materials grown under tissue culture conditions but was not present in those performed from healthy plant materials. The sensitivity of dot blot and Southern blot hybridizations for the detection of BBTV was also performed for the detection of BBTV.

Ultra sensitive label free surface enhanced Raman spectroscopy method for the detection of biomolecules

We present a proof of concept for a novel nanosensor for the detection of ultra-trace amounts of bio-active molecules in complex matrices. The nanosensor is comprised of gold nanoparticles with an ultra-thin silica shell and antibody surface attachment, which allows for the immobilization and direct detection of bio-active molecules by surface enhanced Raman spectroscopy (SERS) without requiring a Raman label. The ultra-thin passive layer (~1.3 nm thickness) prevents competing molecules from binding non-selectively to the gold surface without compromising the signal enhancement. The antibodies attached on the surface of the nanoparticles selectively bind to the target molecule with high affinity. The interaction between the nanosensor and the target analyte result in conformational rearrangements of the antibody binding sites, leading to significant changes in the surface enhanced Raman spectra of the nanoparticles when compared to the spectra of the un-reacted nanoparticles. Nanosensors of this design targeting the bio-active compounds erythropoietin and caffeine were able to detect ultra-trace amounts the analyte to the lower quantification limits of 3.5×10−13 M and 1×10−9 M, respectively.

Tunable “Nano-Shearing” : A physical mechanism to displace nonspecific cell adhesion during rare cell detection

We report a tunable alternating current electrohydrodynamic (ac-EHD) force which drives lateran fluid motion within a few nanometers of an electrode surface. Because the magnitude of this fluid shear force can be tuned externally (e.g., via the application of an ac electric field), it provides a new capability to physically displace weakly (nonspecifically) bound cellular analytes. To demonstrate the utility of the tunable nanoshearing phenomenon, we present data on purpose-built microfluidic devices that employ ac-EHD force to remove nonspecific adsorption of molecular and cellular species. Here, we show that an ac-EHD device containing asymmetric planar and microtip electrode pairs resulted in a 4-fold reduction in nonspecific adsorption of blood cells and also captured breast cancer cells in blood, with high efficiency (approximately 87%) and specificity. We therefore feel that this new capability of externally tuning and manipulating fluid flow could have wide applications as an innovative approach to enhance the specific capture of rare cells such as cancer cells in blood.

Improving the detection of donations within the RHD negative blood donor panel which weakly express the RHD antigen

This project improved the detection and classification of very weakly expressed RhD variants in the Australian blood donor panel and contributed to the knowledge of anti-D reactivity patterns of RHD alleles that are undescribed. As such, the management of donations possessing these RHD alleles can be improved upon and the overall safety of transfusion medicine pertaining to the Rh blood group system will be increased. Future projects at ARCBS will be able to utilise the procedures developed in this project, thereby decreasing throughput time. The specificity of current testing will be improved and the need for outsourced RHD testing diminished.

Plasma-enabled graded nanotube biosensing arrays on a Si nanodevice platform : catalyst-free integration and in situ detection of nucleation events

Low-temperature plasmas in direct contact with arbitrary, written linear features on a Si wafer enable catalyst-free integration of carbon nanotubes into a Si-based nanodevice platform and in situ resolution of individual nucleation events. The graded nanotube arrays show reliable, reproducible, and competitive performance in electron field emission and biosensing nanodevices.

Asymptotic minimax robust and misspecified Lorden quickest change detection for dependent stochastic processes

The quick detection of an abrupt unknown change in the conditional distribution of a dependent stochastic process has numerous applications. In this paper, we pose a minimax robust quickest change detection problem for cases where there is uncertainty about the post-change conditional distribution. Our minimax robust formulation is based on the popular Lorden criteria of optimal quickest change detection. Under a condition on the set of possible post-change distributions, we show that the widely known cumulative sum (CUSUM) rule is asymptotically minimax robust under our Lorden minimax robust formulation as a false alarm constraint becomes more strict. We also establish general asymptotic bounds on the detection delay of misspecified CUSUM rules (i.e. CUSUM rules that are designed with post- change distributions that differ from those of the observed sequence). We exploit these bounds to compare the delay performance of asymptotically minimax robust, asymptotically optimal, and other misspecified CUSUM rules. In simulation examples, we illustrate that asymptotically minimax robust CUSUM rules can provide better detection delay performance at greatly reduced computation effort compared to competing generalised likelihood ratio procedures.

Detection of sinkhole attack in wireless sensor networks

Generally wireless sensor networks rely of many-to-one communication approach for data gathering. This approach is extremely susceptible to sinkhole attack, where an intruder attracts surrounding nodes with unfaithful routing information, and subsequently presents selective forwarding or change the data that carry through it. A sinkhole attack causes an important threat to sensor networks and it should be considered that the sensor nodes are mostly spread out in open areas and of weak computation and battery power. In order to detect the intruder in a sinkhole attack this paper suggests an algorithm which firstly finds a group of suspected nodes by analyzing the consistency of data. Then, the intruder is recognized efficiently in the group by checking the network flow information. The proposed algorithm's performance has been evaluated by using numerical analysis and simulations. Therefore, accuracy and efficiency of algorithm would be verified.

Telomerase activity : detection and clinical implications in human cancer

Telomerase is an extremely important enzyme required for the immortalisation of tumour cells. Because the gene is activated in the vast majority of tumour tissues and remains unused in most somatic cells, it represents a marker with huge diagnostic, prognostic and treatment implications in cancer. This article summarises the basic structure and functions of telomerase and considers its clinical implications in colorectal and other cancers.

Detection of dynamic primary user with cooperative spectrum sensing

In this paper we demonstrate that existing cooperative spectrum sensing formulated for static primary users cannot accurately detect dynamic primary users regardless of the information fusion method. Performance error occurs as the sensing parameters calculated by the conventional detector result in sensing performance that violates the sensing requirements. Furthermore, the error is accumulated and compounded by the number of cooperating nodes. To address this limitation, we design and implement the duty cycle detection model for the context of cooperative spectrum sensing to accurately calculate the sensing parameters that satisfy the sensing requirements. We show that longer sensing duration is required to compensate for dynamic primary user traffic.

Modelling total duration of traffic incidents including incident detection and recovery time

Traffic incidents are key contributors to non-recurrent congestion, potentially generating significant delay. Factors that influence the duration of incidents are important to understand so that effective mitigation strategies can be implemented. To identify and quantify the effects of influential factors, a methodology for studying total incident duration based on historical data from an ‘integrated database’ is proposed. Incident duration models are developed using a selected freeway segment in the Southeast Queensland, Australia network. The models include incident detection and recovery time as components of incident duration. A hazard-based duration modelling approach is applied to model incident duration as a function of a variety of factors that influence traffic incident duration. Parametric accelerated failure time survival models are developed to capture heterogeneity as a function of explanatory variables, with both fixed and random parameters specifications. The analysis reveals that factors affecting incident duration include incident characteristics (severity, type, injury, medical requirements, etc.), infrastructure characteristics (roadway shoulder availability), time of day, and traffic characteristics. The results indicate that event type durations are uniquely different, thus requiring different responses to effectively clear them. Furthermore, the results highlight the presence of unobserved incident duration heterogeneity as captured by the random parameter models, suggesting that additional factors need to be considered in future modelling efforts.

Outbreak detection algorithms for seasonal disease data : a case study using Ross River virus disease

Background Detection of outbreaks is an important part of disease surveillance. Although many algorithms have been designed for detecting outbreaks, few have been specifically assessed against diseases that have distinct seasonal incidence patterns, such as those caused by vector-borne pathogens. Methods We applied five previously reported outbreak detection algorithms to Ross River virus (RRV) disease data (1991-2007) for the four local government areas (LGAs) of Brisbane, Emerald, Redland and Townsville in Queensland, Australia. The methods used were the Early Aberration Reporting System (EARS) C1, C2 and C3 methods, negative binomial cusum (NBC), historical limits method (HLM), Poisson outbreak detection (POD) method and the purely temporal SaTScan analysis. Seasonally-adjusted variants of the NBC and SaTScan methods were developed. Some of the algorithms were applied using a range of parameter values, resulting in 17 variants of the five algorithms. Results The 9,188 RRV disease notifications that occurred in the four selected regions over the study period showed marked seasonality, which adversely affected the performance of some of the outbreak detection algorithms. Most of the methods examined were able to detect the same major events. The exception was the seasonally-adjusted NBC methods that detected an excess of short signals. The NBC, POD and temporal SaTScan algorithms were the only methods that consistently had high true positive rates and low false positive and false negative rates across the four study areas. The timeliness of outbreak signals generated by each method was also compared but there was no consistency across outbreaks and LGAs. Conclusions This study has highlighted several issues associated with applying outbreak detection algorithms to seasonal disease data. In lieu of a true gold standard, a quantitative comparison is difficult and caution should be taken when interpreting the true positives, false positives, sensitivity and specificity.

Topic dependent language modelling for spoken term detection

This paper investigates the effect of topic dependent language models (TDLM) on phonetic spoken term detection (STD) using dynamic match lattice spotting (DMLS). Phonetic STD consists of two steps: indexing and search. The accuracy of indexing audio segments into phone sequences using phone recognition methods directly affects the accuracy of the final STD system. If the topic of a document in known, recognizing the spoken words and indexing them to an intermediate representation is an easier task and consequently, detecting a search word in it will be more accurate and robust. In this paper, we propose the use of TDLMs in the indexing stage to improve the accuracy of STD in situations where the topic of the audio document is known in advance. It is shown that using TDLMs instead of the traditional general language model (GLM) improves STD performance according to figure of merit (FOM) criteria.

Studying upper-limb kinematic using inertial sensors embedded in smartphones

Background: In recent years, there have been investigations concerning upper-limbs kinematics by various devices. The latest generation of smartphones often includes inertial sensors with subunits which can detect inertial kinematics. The use of smartphones is presented as a convenient and portable analysis method for studying kinematics in terms of angular mobility and linear acceleration Objective: The aim of this study was to study humerus kinematics through six physical properties that correspond to angular mobility and acceleration in the three axes of space, obtained by a smartphone. Methods: This cross-sectional study recruited healthy young adult subjects. Descriptive and anthropometric independent variables related to age, gender, weight, size, and BMI were included. Six physical properties were included corresponding to two dependent variables for each of three special axes: mobility angle (degrees) and lineal acceleration (meters/seconds2), which were obtained thought the inertial measurement sensor embedded in the iPhone4 smartphone equipped with three two elements for the detection of kinematic variables: a gyroscope and an accelerometer. Apple uses an LIS302DL accelerometer in the iPhone4. The application used to obtain kinematic data was xSensor Pro, Crossbow Technology, Inc., available at the Apple AppStore. The iPhone4 has storage capacity of 20MB. The data-sampling rate was set to 32 Hz, and the data for each analytical task was transmitted as email for analysis and postprocessing The iPhone4 was placed in the right half of the body of each subject located in the middle third of the humerus slightly posterior snugly secured by a neoprene fixation belt. Tasks were explained concisely and clearly. The beginning and the end were decided by a verbal order by the researcher. Participants were placed standing, starting from neutral position, performing the following analytical tasks: 180º right shoulder abduction (eight repetitions) and, after a break of about 3 minutes, 180º right shoulder flexion (eight repetitions). Both tasks were performed with the elbow extended, wrist in neutral position and the palmar area of the hand toward the midline at the beginning and end of the movement. Results: A total of 11 subjects (8 men, 3 woman) were measured, whose mean of age was 24.7 years (SD = 4.22 years) and their average BMI was 22.64 Kg/m2 (SD = 2.29 Kg/m2). The mean of angular mobility collected by the smartphone was bigger in pitch axis for flexion (= 157.28°, SD= 12.35°) and abduction (= 151.71°, SD= 9.70°). With regard to acceleration, the highest peak mean value was shown in the Y motion axis during flexion (= 19.5°/s2, SD = 0.8°/s2) and abduction (= 19.4°/s2, SD = 0.8°/s2). Also, descriptive graphics of analytical tasks performed were obtained. Conclusions: This study shows how humerus contributes to upper-limb motion and it identified movement patterns. Therefore, it supports smartphone as a useful device to analyze upper-limb kinematics. Thanks to this study it´s possible to develop a simple application that facilitates the evaluation of the patient.