Investigating transport of charged nanoparticles by multiphoton fluorescence correlation spectroscopy (MPFCS)

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2007.Includes bibliographical references (leaves 82-85).Nanoparticles have been demonstrated as a promising new generation of specific imaging agents and targeted delivery vehicles for the diagnosis and treatment of solid tumors. Nonetheless, for optimal therapy of tumors, the nanoparticles must penetrate the tumor interstitial matrix to reach the cancer cells. This thesis describes the development of a multiphoton fluorescence correlation spectroscopy (MPFCS) system and its utilization to probe the effect of charge on the diffusion of quantum dot (QD) nanocrystals in collagen and collagen-hyaluronan (HA) composite gel models of human colon adenocarcinoma (LS174T). The MPFCS system was integrated with a multiphoton laser-scanning microscope (MPLSM) to enable visualization of QD distribution and collagen organization, as well as diffusion measurements. QDs of three different charges by modifying the surface of pre-made CdSe/CdZnS QDs with dihydrolipoic acid (DHLA), DHLA-polyethyleneglycol (DHLA-PEG) and amino-functionalized DHLA-PEG (DHLA-PEG-NH2). Aggregation was observed in QD-DHLA (4-potential = -31.12 mV) and QD-DHLA-PEG-NH2 (4-potential = +37.39 mV) samples in gels, but the distribution of QD-DHLA-PEG (ý-potential = -18.16 mV) was uniform. FCS measurements were performed for each QD sample in both gel models. Experimental data indicated anomalous subdiffusion of QDs in both gels with all samples having the same time exponent. The transport coefficient of QD-DHLA-PEG was significantly higher than QD-DHLA and QD-DHLA-PEG-NH2. A two-component free diffusion model also provided a good fit for the data, but did not provide a clear picture on the role of charge in diffusion. Our experiments suggest that anionic and cationic nanoparticles experience more hindrance compared to neutral, PEGylated nanoparticles in both collagen and collagen-HA gels.by Ming-Zher Poh.S.M

Continuous assessment of epileptic seizures with wrist-worn biosensors

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 145-159).Epilepsy is a neurological disorder characterized predominantly by an enduring predisposition to generate epileptic seizures. The apprehension about injury, or even death, resulting from a seizure often overshadows the lives of those unable to achieve complete seizure control. Moreover, the risk of sudden death in people with epilepsy is 24 times higher compared to the general population and the pathophysiology of sudden unexpected death in epilepsy (SUDEP) remains unclear. This thesis describes the development of a wearable electrodermal activity (EDA) and accelerometry (ACM) biosensor, and demonstrates its clinical utility in the assessment of epileptic seizures. The first section presents the development of a wrist-worn sensor that can provide comfortable and continuous measurements of EDA, a sensitive index of sympathetic activity, and ACM over extensive periods of time. The wearable biosensor achieved high correlations with a Food and Drug Administration (FDA) approved system for the measurement of EDA during various classic arousal experiments. This device offers the unprecedented ability to perform comfortable, long-term, and in situ assessment of EDA and ACM. The second section describes the autonomic alterations that accompany epileptic seizures uncovered using the wearable EDA biosensor and time-frequency mapping of heart rate variability. We observed that the post-ictal period was characterized by a surge in sympathetic sudomotor and cardiac activity coinciding with vagal withdrawal and impaired reactivation. The impact of autonomic dysregulation was more pronounced after generalized tonic-clonic seizures compared to complex partial seizures. Importantly, we found that the intensity of both sympathetic activation and parasympathetic suppression increased approximately linearly with duration of post-ictal EEG suppression, a possible marker for the risk of SUDEP. These results highlight a critical window of post-ictal autonomic dysregulation that may be relevant in the pathogenesis of SUDEP and hint at the possibility for assessment of SUDEP risk by autonomic biomarkers. Lastly, this thesis presents a novel algorithm for generalized tonic-clonic seizure detection with the use of EDA and ACM. The algorithm was tested on 4213 hours (176 days) of recordings from 80 patients containing a wide range of ordinary daily activities and detected 15/16 (94%) tonic-clonic seizures with a low rate of false alarms (<; 1 per 24 h). It is anticipated that the proposed wearable biosensor and seizure detection algorithm will provide an ambulatory seizure alarm and improve the quality of life of patients with uncontrolled tonic-clonic seizures.by Ming-Zher Poh.Ph.D

Detecting deception and suspicion in dyadic game interactions

In this paper we focus on detection of deception and suspicion from electrodermal activity (EDA) measured on left and right wrists during a dyadic game interaction. We aim to answer three research questions: (i) Is it possible to reliably distinguish deception from truth based on EDA measurements during a dyadic game interaction? (ii) Is it possible to reliably distinguish the state of suspicion from trust based on EDA measurements during a card game? (iii) What is the relative importance of EDA measured on left and right wrists? To answer our research questions we conducted a study in which 20 participants were playing the game Cheat in pairs with one EDA sensor placed on each of their wrists. Our experimental results show that EDA measures from left and right wrists provide more information for suspicion detection than for deception detection and that the person-dependent detection is more reliable than the person-independent detection. In particular, classifying the EDA signal with Support Vector Machine (SVM) yields accuracies of 52% and 57% for person-independent prediction of deception and suspicion respectively, and 63% and 76% for person-dependent prediction of deception and suspicion respectively. Also, we found that: (i) the optimal interval of informative EDA signal for deception detection is about 1 s while it is around 3.5 s for suspicion detection; (ii) the EDA signal relevant for deception/ suspicion detection can be captured after around 3.0 seconds after a stimulus occurrence regardless of the stimulus type (deception/ truthfulness/suspicion/trust); and that (iii) features extracted from EDA from both wrists are important for classification of both deception and suspicion. To the best of our knowledge, this is the firstwork that uses EDA data to automatically detect both deception and suspicion in a dyadic game interaction setting.N

Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors

Objective New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors. Methods Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic–clonic seizures and 49 focal to bilateral tonic–clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses. Results The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had <1 false alarm every 4 days, with an FAR below their seizure frequency. When increasing the sensitivity to 100% (no missed seizures), the FAR is up to 13 times lower than with the previous detector. Furthermore, all detections occurred before the seizure ended, providing reasonable latency (median = 29.3 s, range = 14.8–151 s). Automatically estimated seizure durations were correlated with true durations, enabling reliable annotations. Finally, EDA measurements confirmed the presence of postictal autonomic dysfunction, exhibiting a significant rise in 73% of the convulsive seizures. Significance The proposed multimodal wrist-worn convulsive seizure detectors provide seizure counts that are more accurate than previous automated detectors and typical patient self-reports, while maintaining a tolerable FAR for ambulatory monitoring. Furthermore, the multimodal system provides an objective description of motor behavior and autonomic dysfunction, aimed at enriching seizure characterization, with potential utility for SUDEP warning

Motion-Tolerant Magnetic Earring Sensor and Wireless Earpiece for Wearable Photoplethysmography

This paper addresses the design considerations and critical evaluation of a novel embodiment for wearable photoplethysmography (PPG) comprising a magnetic earring sensor and wireless earpiece. The miniaturized sensor can be worn comfortably on the earlobe and contains an embedded accelerometer to provide motion reference for adaptive noise cancellation. The compact wireless earpiece provides analog signal conditioning and acts as a data-forwarding device via a radio frequency transceiver. Using Bland-Altman and correlation analysis, we evaluated the performance of the proposed system against an FDA-approved ECG measurement device during daily activities. The mean ?? standard deviation (SD) of the differences between heart rate measurements from the proposed device and ECG (expressed as percentage of the average between the two techniques) along with the 95% limits of agreement (LOA = ??1.96 SD) was 0.62% ?? 4.51% (LOA = -8.23% and 9.46%), -0.49% ?? 8.65% (-17.39% and 16.42%), and -0.32% ?? 10.63% (-21.15% and 20.52%) during standing, walking, and running, respectively. Linear regression indicated a high correlation between the two measurements across the three evaluated conditions (r = 0.97, 0.82, and 0.76, respectively with p < 0.001). The new earring PPG system provides a platform for comfortable, robust, unobtrusive, and discreet monitoring of cardiovascular function

Wearable sensors: Opportunities and challenges for low-cost health care

Wearable sensors enable long-term continuous physiological monitoring, which is important for the treatment and management of many chronic illnesses, neurological disorders, and mental health issues. Examples include: diabetes, autism spectrum disorder (ASD), depression, drug addition, and anxiety disorders. In this paper, we present a few mobile health technologies developed by our group and also discuss emerging opportunities as well as existing challenges. Technologies presented include wearable sensors for electrodermal activity (EDA) and mobile plethysmography as well as mobile phones and the supporting wireless network architecture

A Wearable Sensor for Unobtrusive, Long-Term Assessment of Electrodermal Activity

Electrodermal activity (EDA) is a sensitive index of sympathetic nervous system activity. Due to the lack of sensors that can be worn comfortably during normal daily activity and over extensive periods of time, research in this area is limited to laboratory settings or artificial clinical environments. We developed a novel, unobtrusive, nonstigmatizing, wrist-worn integrated sensor, and present, for the very first time, a demonstration of long-term, continuous assessment of EDA outside of a laboratory setting. We evaluated the performance of our device against a Food and Drug Administration (FDA) approved system for the measurement of EDA during physical, cognitive, as well as emotional stressors at both palmar and distal forearm sites, and found high correlations across all the tests. We also evaluated the choice of electrode material by comparing conductive fabric with Ag/AgCl electrodes and discuss the limitations found. An important result presented in this paper is evidence that the distal forearm is a viable alternative to the traditional palmar sites for EDA measurements. Our device offers the unprecedented ability to perform comfortable, long-term, and in situ assessment of EDA. This paper opens up opportunities for future investigations that were previously not feasible, and could have far-reaching implications for diagnosis and understanding of psychological or neurological conditions.Nancy Lurie Marks Family Foundatio

Non-contact, automated cardiac pulse measurements using video imaging and blind source separation

Remote measurements of the cardiac pulse can provide comfortable physiological assessment without electrodes. However, attempts so far are non-automated, susceptible to motion artifacts and typically expensive. In this paper, we introduce a new methodology that overcomes these problems. This novel approach can be applied to color video recordings of the human face and is based on automatic face tracking along with blind source separation of the color channels into independent components. Using Bland-Altman and correlation analysis, we compared the cardiac pulse rate extracted from videos recorded by a basic webcam to an FDA-approved finger blood volume pulse (BVP) sensor and achieved high accuracy and correlation even in the presence of movement artifacts. Furthermore, we applied this technique to perform heart rate measurements from three participants simultaneously. This is the first demonstration of a low-cost accurate video-based method for contact-free heart rate measurements that is automated, motion-tolerant and capable of performing concomitant measurements on more than one person at a time.Massachusetts Institute of Technology. Media LaboratoryThings That Think ConsortiumNancy Lurie Marks Family Foundatio