Bounds in the Sensitivity of BioMEMS Devices for Cell Detection

This paper presents an ongoing effort to characterize performance and reliability of micro electromechanical systems used for biomedical diagnostics (BioMEMS). In order to study the interactions of human osteosarcoma (HOS) cells with BioMEMS devices, cultures were performed on silicon (Si) surfaces as well as silicon surfaces coated with 50 nm of titanium (Ti). Cell spreading on the surfaces was observed over time for up to 2 hours. It was seen that titanium coated silicon surfaces have the potential to provide a better interface for BioMEMS devices, due to enhanced adherence and spreading of the cells on these surfaces. Atomic force microscope (AFM) cantilevers were used as cell detection sensors. These cantilevers were coated with 50nm of titanium metal to provide a cell friendly surface. Theoretical models were then developed for the prediction of the vibrational responses of the AFM cantilevers before and after cell attachment. The models were used to relate the experimentally observed changes in frequency to the number of cells that are attached on the cantilever. The bounds in the possible frequency changes were determined within a theoretical framework. From experimentally calculated values for the mass of cells, random number simulations were carried out to determine the probability of cell attachment as a function of the change in resonance frequency of the cantilever sensor. The implications of the results are then discussed for the future reliability modeling of the sensor.     

Development and preliminary evaluation of a slide latex agglutination assay for detection of Clostridium perfringens type A enterotoxin

A slide latex agglutination (SLA) assay was developed for rapid screening for Clostridium perfringens type A enterotoxin (CPE). SLA specifically detected CPE added to buffer or normal feces (sensitivity limit of 1 μg CPE/g feces). Using clinical fecal samples from C. perfringens food poisoning cases, a strong correlation was shown between (1) SLA results and results from other CPE assays and (2) between SLA results and illness status.     

The relationship between cardiovascular reactivity and heartbeat detection

This experiment tested the hypothesis that inotropic cardiovascular reactivity to stress is related to performance on heartbeat discrimination tasks. The experiment also compared the efficacy of a specific modification of two popular heartbeat discrimination paradigms, Whitehead's and Katkin's. Subjects were 48 male undergraduates who performed both discrimination tasks and then were subjected to mental arithmetic stress. Results indicated that high cardiovascular reactors were better detectors than low reactors. Results also indicated that subjects performed better on the modified Whitehead task than on the modified Katkin task.     

Strategic control and medial frontal negativity: beyond errors and response conflict

Errors in timed choice tasks typically produce an error-related negativity (ERN) in the event-related potential (ERP). The error specificity of the ERN has been challenged by studies showing a correct response negativity (CRN). Forty-five participants engaged in a flanker task in which both compatibility between flankers and target and the probability of compatible flankers were manipulated. Correct responses elicited a CRN, the amplitude of which increased with the degree of mismatch between the presence of conflict and conflict probability, even on low-conflict (compatible) trials. The fronto-central N2 component was larger on high-conflict (incompatible) correct response trials. However, in contrast to some recent accounts, this N2 was largest for highly probable stimuli. These findings suggest revision to models of the effects of conflict on response-related negativity to account for strategic adjustments made in preparation for the response.     

Perceptual Performance as a Function of Intra-Cycle Cardiac Activity

The purpose of the experiment was to test the hypothesis of a systematic change in perceptual performance within a single cardiac cycle due to the activity of the baroreceptors in carotid sinus. As an index of perceptual performance the d_s-parameter from signal detection theory (TSD) was used. A 1000 Hz sine tone had to be detected in a background of white noise. Each of 4 subjects received on the average 4605 noise or noise plus tone stimuli distributed over 10 experimental sessions. When comparing performance during time intervals before and after baroreceptor activity onset no significant difference was found. Also, when tracing perceptual performance over the whole cardiac cycle in steps of 66,100, and 200 msec, no systematic variation could be detected. For steps of 33 msec a rhythmic pulsation of perceptual performance of about 8 Hz appeared. An influence of electrical activity of the brain on perceptual performance was postulated. This activity would have to be time-locked to carotid sinus baroreceptor activity.     

The dorsomedial frontal cortex of the macaca monkey: fixation and saccade-related activity

Summary The activity of 249 neurons in the dorsomedial frontal cortex was studied in two macaque monkeys. The animals were trained to release a bar when a visual stimulus changed color in order to receive reward. An acoustic cue signaled the start of a series of trials to the animal, which was then free to begin each trial at will. The monkeys tended to fixate the visual stimuli and to make saccades when the stimuli moved. The monkeys were neither rewarded for making proper eye movements nor punished for making extraneous ones. We found neurons whose discharge was related to various movements including those of the eye, neck, and arm. In this report, we describe the properties of neurons that showed activity related to visual fixation and saccadic eye movement. Fixation neurons discharged during active fixation with the eye in a given position in the orbit, but did not discharge when the eye occupied the same orbital positions during nonactive fixation. These neurons showed neither a classic nor a complex visual receptive field, nor a foveal receptive visual field. Electrical stimulation at the site of the fixation neurons often drove the eye to the orbital position associated with maximal activity of the cell. Several different kinds of neurons were found to discharge before saccades: 1) checking-saccade neurons, which discharged when the monkeys made self-generated saccades to extinguish LED's; 2) novelty-detection saccade neurons, which discharged before the first saccade made to a new visual target but whose activity waned with successive presentations of the same target. These results suggest that the dorsomedial frontal cortex is involved in attentive fixation. We hypothesize that the fixation neurons may be involved in codifying the saccade toward a target. We propose that their involvement in arm-eye-head motor-planning rests primarily in targeting the goal of the movement. The fact that saccaderelated neurons discharge when the saccades are self initiated, implies that this area of the cortex may share the control of voluntary saccades with the frontal eye fields and that the activation is involved in intentional motor processes.     

Amplification of rhinovirus specific nucleic acids from clinical samples using the polymerase chain reaction

We describe a novel method for the detection of human rhinoviruses in clinical samples, using the polymerase chain reaction. Two synthetic oligonucleotide primers were produced that bind in the 5' noncoding region of all rhinovirus serotypes tested, about 350 nucleotides apart, and were used to prime polymerase chain reaction amplification of the intervening stretch of DNA. The product of this reaction, which can be clearly visualized by gel electrophoresis, is a discrete 380 bp band, the occurrence of which is diagnostic of the presence of a rhinovirus in the clinical sample analysed. The technique, which is rapid, sensitive, and reliable, has been used successfully for all the different rhinovirus serotypes tested to date in our laboratory. However, the sensitivity of detection is greatly dependent on the inclusion of both tRNA and vanadyl complexes during the viral RNA extraction process. Using this technique, under optimal conditions, we were able to detect virus in clinical samples with titres as low as TCID50 10(2.5).     

Sensitivity to mechanical stimuli and the role of general sensory and perceptual processes in heartbeat detection

Sensitivity to heartbeat sensations is commonly assessed using tasks that require individuals to judge the simultaneity of heartbeats and tones. In two experiments, we investigated the suitability of this paradigm for examining cardioception. In the first experiment, participants judged the simultaneity of near–threshold vibrations and suprathreshold tones. Precision in judging vibration–tone simultaneity was directly related to the detectability of the mechanical stimuli, thereby supporting use of the simultaneity paradigm to assess heartbeat detection. In the second experiment, we examined the influences of sensitivity to mechanical stimuli and the ability to make intermodality simultaneity judgments on the precision of heartbeat detection. We measured participants' vibrotactile thresholds, precision in judging light–tone simultaneity, and precision in judging heartbeat–tone simultaneity. The ability to judge the simultaneity of lights and tones accounted for 24.3% of the variance in precision of heartbeat detection, and mechanical sensitivity accounted for a further 8.5%.     

Effects of data limitations on heartbeat detection in the method of constant stimuli

In the method of constant stimuli applied to measuring heartbeat detection, subjects judge the simultaneity of heartbeats and exteroceptive comparison stimuli presented at various intervals after the R-wave (0, 100, 200, 300, 400, and 500 ms). Using versions of this procedure, investigators have found that between 20% (Yates, Jones, Marie, & Hogben, 1985) and 54% (Brener, Liu, & Ring, 1993) of subjects can detect heartbeat sensations. Whereas Yates et al. used a single comparison stimulus on each trial and Brener et al. used 10, the present study examined whether this disparity in heartbeat detection performance could be attributed to the number of comparison stimuli presented on each trial. In each of 360 trials, 30 subjects judged the simultaneity of heartbeat sensations and tones following 1, 5, or 10 comparison stimulus presentations. Significantly fewer subjects met the criterion for heartbeat detection with I tone presentation (13%) than with either 5 (43%) or 10 (47%) tone presentations. It is concluded that a single stimulus presentation imposes data limitations that result in underestimation of the accuracy of heartbeat detection. The presentation of at least 5 stimuli in each trial alleviates this limitation.