Elad D.,Aviv Biomedical, Inc. |
Kozlovsky P.,Aviv Biomedical, Inc. |
Blum O.,Aviv Biomedical, Inc. |
Laine A.F.,Columbia University |
And 6 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014
How do infants extract milk during breast-feeding? We have resolved a century-long scientific controversy, whether it is sucking of the milk by subatmospheric pressure or mouthing of the nipple- areola complex to induce a peristaltic-like extraction mechanism. Breast-feeding is a dynamic process, which requires coupling between periodic motions of the infant's jaws, undulation of the tongue, and the breast milk ejection reflex. The physical mechanisms executed by the infant have been intriguing topics. We used an objective and dynamic analysis of ultrasound (US) movie clips acquired during breast-feeding to explore the tongue dynamic characteristics. Then, we developed a new 3D biophysical model of the breast and lactiferous tubes that enables the mimicking of dynamic characteristics observed in US imaging during breastfeeding, and thereby, exploration of the biomechanical aspects of breast-feeding. We have shown, for the first time to our knowledge, that latch-on to draw the nipple-areola complex into the infant mouth, as well as milk extraction during breast-feeding, require development of time-varying subatmospheric pressures within the infant's oral cavity. Analysis of the US movies clearly demonstrated that tongue motility during breast-feeding was fairly periodic. The anterior tongue, which is wedged between the nipple-areola complex and the lower lips, moves as a rigid body with the cycling motion of the mandible, while the posterior section of the tongue undulates in a pattern similar to a propagating peristaltic wave, which is essential for swallowing.
Roitshtain D.,Aviv Biomedical, Inc. |
Wolbromsky L.,Aviv Biomedical, Inc. |
Bal E.,Aviv Biomedical, Inc. |
Greenspan H.,Aviv Biomedical, Inc. |
Shaked N.T.,Aviv Biomedical, Inc.
Cytometry Part A | Year: 2017
We present cytometric classification of live healthy and cancerous cells by using the spatial morphological and textural information found in the label-free quantitative phase images of the cells. We compare both healthy cells to primary tumor cells and primary tumor cells to metastatic cancer cells, where tumor biopsies and normal tissues were isolated from the same individuals. To mimic analysis of liquid biopsies by flow cytometry, the cells were imaged while unattached to the substrate. We used low-coherence off-axis interferometric phase microscopy setup, which allows a single-exposure acquisition mode, and thus is suitable for quantitative imaging of dynamic cells during flow. After acquisition, the optical path delay maps of the cells were extracted and then used to calculate 15 parameters derived from the cellular 3D morphology and texture. Upon analyzing tens of cells in each group, we found high statistical significance in the difference between the groups in most of the parameters calculated, with the same trends for all statistically significant parameters. Furthermore, a specially designed machine learning algorithm, implemented on the phase map extracted features, classified the correct cell type (healthy/cancer/metastatic) with 81-93% sensitivity and 81-99% specificity. The quantitative phase imaging approach for liquid biopsies presented in this paper could be the basis for advanced techniques of staging freshly isolated live cancer cells in imaging flow cytometers. © 2017 International Society for Advancement of Cytometry.
Dana A.,Aviv Biomedical, Inc. |
Tuller T.,Aviv Biomedical, Inc. |
Tuller T.,Tel Aviv University
G3: Genes, Genomes, Genetics | Year: 2015
Gene translation modeling and prediction is a fundamental problem that has numerous biomedical implementations. In this work we present a novel, user-friendly tool/index for calculating the mean of the typical decoding rates that enables predicting translation elongation efficiency of protein coding genes for different tissue types, developmental stages, and experimental conditions. The suggested translation efficiency index is based on the analysis of the organism's ribosome profiling data. This index could be used for example to predict changes in translation elongation efficiency of lowly expressed genes that usually have relatively low and/or biased ribosomal densities and protein levels measurements, or can be used for example for predicting translation efficiency of new genetically engineered genes. We demonstrate the usability of this index via the analysis of six organisms in different tissues and developmental stages. Distributable cross platform application and guideline are available for download at: http://www.cs. tau.ac.il/~tamirtul/MTDR/MTDR_Install.html. © 2015 Dana and Tuller.
Zur H.,Aviv Biomedical, Inc. |
Tuller T.,Aviv Biomedical, Inc. |
Tuller T.,Tel Aviv University
Bioinformatics | Year: 2015
Motivation: Dozens of studies in recent years have demonstrated that codon usage encodes various aspects related to all stages of gene expression regulation. When relevant high-quality large-scale gene expression data are available, it is possible to statistically infer and model these signals, enabling analysing and engineering gene expression. However, when these data are not available, it is impossible to infer and validate such models. Results: In this current study, we suggest Chimera-an unsupervised computationally efficient approach for exploiting hidden high-dimensional information related to the way gene expression is encoded in the open reading frame (ORF), based solely on the genome of the analysed organism. One version of the approach, named Chimera Average Repetitive Substring (ChimeraARS), estimates the adaptability of an ORF to the intracellular gene expression machinery of a genome (host), by computing its tendency to include long substrings that appear in its coding sequences; the second version, named ChimeraMap, engineers the codons of a protein such that it will include long substrings of codons that appear in the host coding sequences, improving its adaptation to a new hostâ (tm)s gene expression machinery. We demonstrate the applicability of the new approach for analysing and engineering heterologous genes and for analysing endogenous genes. Specifically, focusing on Escherichia coli, we show that it can exploit information that cannot be detected by conventional approaches (e.g. the CAI-Codon Adaptation Index), which only consider single codon distributions; for example, we report correlations of up to 0.67 for the ChimeraARS measure with heterologous gene expression, when the CAI yielded no correlation. Availability and implementation: For non-commercial purposes, the code of the Chimera approach can be downloaded from http://www.cs.tau.ac.il/tamirtul/Chimera/download.htm. © 2014 The Author.
Barkay-Olami H.,Aviv Biomedical, Inc. |
Zilberman M.,Aviv Biomedical, Inc.
Journal of Biomedical Materials Research - Part B Applied Biomaterials | Year: 2015
Use of naturally derived materials for biomedical applications is steadily increasing. Soy protein has advantages over various types of natural proteins employed for biomedical applications due to its low price, nonanimal origin, and relatively long storage time and stability. In the current study, blends of soy protein with other polymers (gelatin, alginate, pectin, polyvinyl alcohol, and polyethylene glycol) were developed and studied. The mechanical tensile properties of dense films were studied in order to select the best secondary polymer for porous three-dimensional structures. The porous soy-gelatin and soy-alginate structures were then studied for physical properties, degradation behavior, and microstructure. The results show that these blends can be assembled into porous three-dimensional structures by combining chemical crosslinking with freeze-drying. The soy-alginate blends are advantageous over soy-gelatin blends, demonstrated better stability, and degradation time along with controlled swelling behavior due to more effective crosslinking and higher water uptake than soy-gelatin blends. Water vapor transmission rate experiments showed that all porous blend structures were in the desired range for burn treatment [2000-2500 g/(m2 d)] and can be controlled by the crosslinking process. We conclude that these novel porous three-dimensional structures have a high potential for use as scaffolds for tissue engineering, especially for skin regeneration applications. © 2015 Wiley Periodicals, Inc.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 826.99K | Year: 2012
DESCRIPTION (provided by applicant): Uncontrolled hyperbilirubinemia (jaundice) in neonates has long been known to lead to neurological dysfunction including irreversible athetoid cerebral palsy with speech, ocular and hearing impairments, and even death.Contemporary management is based upon monitoring the total serum bilirubin (TBS), taking into account other clinical parameters such as birth weight and gestational age, and administering effective treatment (phototherapy and/or the rare exchange transfusion), if dictated. Unfortunately, the trend towards discharge of apparently healthy neonates from the hospital very soon after birth has made the management of subsequent jaundice more difficult in that population. A long suggested, but not used, better predictor of the neonate's risk for neurological sequelae due to elevated bilirubin is a measure of the capacity to sequester bilirubin in the blood compartment by its binding to serum albumin. The concentration of unbound bilirubin, the driver for bilirubinescaping from the vasculature, can be calculated from the TBS and binding capacitl. Presently existing methods for assaying binding capacity and unbound bilirubin are not facile. However, all these parameters can be directly measured simply in a very smallvolume of whole blood with a special purpose fluorometer, the hematofluorometer, first described years ago, by making use of the natural fluorescence of bilirubin bound to albumin. This technology is amenable to point-of-care use. The aims of this project are to transform the modernized and miniaturized hematofluorometer developed in Phase I into a product suitable for operation in various point-of-care environments, including the intensive care and healthy baby nurseries, the neonatal inpatient clinic, and the pediatrician's office. The first aim is to optimize the basic optical and electronic design: redesin the electronics to support the hospital information management requirements, such as a bar code reader, printer, and interface with a computer, either directly or via the local internet. The second aim is to develop a reagent kit that is easy to use and inexpensive. Phase I work demonstrated that significantly more work is needed to design a kit meeting these requirements, and then scaling this design up into a product that can be mass produced. The third aim is to test the instrument with neonate blood samples in a clinical environment to demonstrate that it well suited to meet the needs. With this goal in mind, Stanford University's Medical School and Children's Hospital has agreed to participate as a subcontractor to evaluate the new technology. With these proposed improvements, the instrument will be ready for the next stages: releasing it to the market for immediate RandD uses and clinical studies, and eventual approval by the FDA for general use. PUBLIC HEALTH RELEVANCE: A long suggested, but not used, better predictor of the neonate's risk for neurological sequelae due to elevated bilirubin is a measure of the capacity to sequester bilirubin in the blood compartment by its binding to serum albumin. The concentration of unbound bilirubin, the driver for bilirubin escaping from the vasculature, can be calculated from the TBS and binding capacitl. Presently existing methods for assaying binding capacity and unbound bilirubin are not facile. However, all these parameters can be directly measured simply in a very small volume of whole blood with a special purpose fluorometer, the hematofluorometer, first described years ago, by making use of the natural fluorescence of bilirubin bound to albumin. This technology is amenable to point-of-care use.The aims of this project are to transform the modernized and miniaturized hematofluorometer developed in Phase I into a product suitable for operation in various point-of-care environments, to complete development of easy-to-use sample handling disposables, and to verify the performance of the system for samples from a specified population of neonates.
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 983.97K | Year: 2016
DESCRIPTION provided by applicant Neonatal hyperbilirubinemia occurs in almost all newborns and may be benign if its progression to extreme hyperbilirubinemia is recognized monitored and prevented or managed in a timely manner Neonatal jaundice carries the risk of neurotoxicity due to the deposition of bilirubin in the central nervous system Most of the bilirubin in plasma is bound to plasma proteins mainly serum albumin Bilirubin binding capacity BBC defines the dynamic relationship between an infantandapos s level of unbound or andquot freeandquot bilirubin and his her ability to andquot tolerateandquot increasing bilirubin loads BBC is not synonymous with albumin Alb levels because Alb binding of bilirubin is confounded by a variety of molecular biologic and metabolic factors While various methods exist to measure BBC none have been successfully commercialized Of these hematofluorometry holds the greatest promise of a device that can be used at the point of care and give rapid and accurate BBC measurements A SBIR Phase I grant demonstrated that such a device is possible A Phase II grant delivered improved devices to neonatal hospitals Published clinical studies with these devices not only collaborated prior knowledge but suggested ways in which BBC measurements may improve existing neonatal care The aims of this project are to transform the modernized hematofluorometers developed in Phases I and II into a final product suitable for operation in a point of care environment in the newborn nursery NICU and neonatal outpatient clinic In year one Avivandapos s goals are to develop and evaluate a andquot singleandquot position hematofluorometer in terms of increased accuracy over prior designs develop and evaluate kit designs that increase the ease of use improve the use of the internal reference develop primary standards for calibration develop validation checks Beginning in year and continuing into year Aviv will perform shelf life tests determine environmental limits of operation integrate a bar code reader and laboratory information management software support internal quality checks into the device and software investigate potential interferences to measurements and incorporate guidance for use into documentation and software During year Aviv will have a commercializable embodiment develop methods and documentation identify partners for manufacturing marketing sales and distribution Concurrent with these activities Stanford Universityandapos s Lucile Packard Childrenandapos s Hospital will conduct clinical studies to evaluate the usefulness of BBC measurements in a clinical setting Experienced consultants in the fields of neonatal care management clinical lab directors and those with hands on experience neonatal intensive care units and clinical labs will be consulted on the suitability of the device and reagent kit The goal is to obtain expert recommendations for the use of the BBC assay to inform additional clinically useful modifications of the hematofluorometer system PUBLIC HEALTH RELEVANCE Management of newborns with elevated unconjugated bilirubin levels in order to prevent bilirubin induced neurological dysfunction BIND and kernicterus remains problematical especially for premature infants The bilirubin binding capacity of albumin BBC is a determinative measure of a neonateandapos s ability to cope with an excessive bilirubin burden This proposal aims to complete the development of a bilirubin hematofluorometer that easily measures BCC at the points of care and initiate its commercialization
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 170.16K | Year: 2010
DESCRIPTION (provided by applicant): Human serum albumin is capable of binding bilirubin with high affinity, thus sequestering it and mitigat- ing its harmful neurological effects in jaundiced newborns. Despite considerable work indicating that the level of bilirubin in the blood relative to the level of albumin binding sites is a key factor in assessing risk for bilirubin associated brain damage, management of neonatal jaundice remains based upon proxies, such as gestational age and birth weight along with the bilirubin level. A number of methods for assaying the bilirubin level now ex- ist. The common approaches determine the total serum bilirubin by wet chemical methods. Methods to assay reserve albumin binding capacity and unbound (mobilized) bilirubin levels in serum have been developed over the years but none have achieved routine use because they remain cumbersome laboratory tests. The pro- posed work is to develop a point-of-care system (a small fluorometer and disposables) that makes use of bili- rubin's natural fluorescence. Bilirubin bound to albumin produces a fluorescence signal that can be detected in raw blood. Assayed by fluorescence this albumin-bound bilirubin level equates to the total serum bilirubin by standard methods since the unbound bilirubin level is always much smaller until albumin binding approaches saturation. The reserve binding capacity for bilirubin can be measured by adding excess bilirubin to the blood, with the increase in fluorescence being due to the newly bound bilirubin. This approach measures the actual binding capacity and naturally takes into account factors such as albumin levels, competing binding by other solutes and weakened binding sites. The basic studies leading to this fluorometric approach were reported more than thirty years ago and prototype laboratory-bound instruments were devised and tested in clinical settings. At that time new manage- ment guidelines in the absence of binding data coupled with wide use of phototherapy obviated their use. With the current practice of very early release of apparently healthy newborns and susbsequent development of jaundice at home, management has become complicated. Interviews with pediatricians on the ground have indicated that an inexpensive and easy to use point-of-care system that requires only a heel stick quantity of blood and essentially no manipulation of the specimen, would provide for better management from the ability to provide a stat bilirubin level alone, and binding data would additionally provide guidance in management that may be more efficient and less costly. Use at crib-side should also benefit the management of the jaundiced hospitalized low-birth-weight and sick neonate. While apparently feasible with modern optoelectronic technology, several design and practical chal- lenges exist for the development of such a small point-of-care system. The proposed work will confront and overcome these challenges. PUBLIC HEALTH RELEVANCE: Kernicterus is a preventable brain injury in neonates, and it is reemerging in the USA (1-5). Present-day methods of assaying bilirubin do not take into account a child's ability to safely sequester bilirubin and must be interpreted in terms of gestational age, age, weight and other factors (6). The proposed hematofluorometer directly measures bilirubin binding and reserve bilirubin binding capacity, and has the potentials to be faster, less expensive and available at the point of care.
Aviv Biomedical, Inc. | Date: 2015-07-22
A hematofluorometer an excitation source configured to generate an excitation beam, a fluorescence detector configured to a fluorescence beam, and a housing configured to receive a reagent kit for detecting bilirubin in a fluid sample. The reagent kit includes a body defining at least one fluid receiving well and an optical window positioned over each at least one fluid receiving well and a light passage window opposite each optical window. Each window is formed of a material having a fluorescence intensity that is of a lower magnitude than the fluorescence to be detected from the bilirubin. A light sensor within the housing is configured to detect light passing through the reagent kit.
Aviv Biomedical, Inc. | Date: 2014-01-14
A reagent kit for detecting bilirubin in a fluid sample. The reagent kit includes a body defining at least one fluid receiving well and an optical window positioned over each at least one fluid receiving well. Each window is formed of a material having a fluorescence intensity that is of a lower magnitude than the fluorescence to be detected from the bilirubin. A hematofluorometer configured to utilize the reagent kit is also disclosed.