OCommBIOSTEC 2016 Abstracts


Full Papers
Paper Nr: 5
Title:

VIRUMILK: Rapid Diagnostic Test for HCMV Detection in Breast Milk from Lactating Women of Preterm Infants Less than 33 Weeks

Authors:

Stéphanie Py, G. Thiriez, Bruno Wacogne, Georges Herbein, Alain Coaquette, Lionel Pazart and Wilfrid Boireau

Abstract: Human cytomegalovirus (HCMV) is the leading cause of neonatal viral infection and can have a significant impact on the neurosensory development of newborns and especially preterm infants. HCMV infection may result from maternal-fetal transmission during pregnancy (congenital infection) or postnatal transmission. While congenital HCMV infection affects about 2-5% of very preterm infants, the risk of postnatal infection, particularly through breast milk, is much higher in this population (prevalence of about 20%). Many learned societies wonder about the interest to inactivate HCMV (by freezing or pasteurization) in breast milk in order to reduce or eliminate contamination of these children. However, freezing is relatively inefficient to reduce contamination and pasteurization drastically alters the nutritional quality of the milk. Therefore, a systematic preventive treatment of breast milk for very preterm infants is not currently recommended. An alternative approach could consist in detecting HCMV in breast milk to target at-risk situations. Currently, viral status of breast milk is not explored in practice and, depending on the health centers, breastfeeding is continued as such or milk is systematically inactivated. To address this problem, and in the current context of breastfeeding promotion, the main objective of VIRUMILK is to develop a simple, rapid and low-cost detection system at patient’s bedside, namely a Rapid Diagnostic Test (RDT) based on lateral flow immunochromatography for HCMV detection in the breast milk from lactating mothers in order to prevent the postnatal HCMV infection of preterm newborns less than 33 weeks. The principle of the test is very easy and is based on a sandwich format. The capture antibody is immobilized directly on the migration membrane. A detection antibody conjugated to colloidal gold will be captured at the Test line when HCMV particles are present in the breast milk sample. Signal at the control line, based on the detection on anti-species antibodies will validate the correct functioning of the lateral flow device. Various interaction experiments have been conducted with “home-made” polyclonal anti-HCMV antibodies, concentrated intracellular HCMV derived from lysed cells and a commercial detection labeled antibody. Results show a capture and/or a detection of HCMV according to the type of experiments. Moreover preliminary positive results were obtained with artificially contaminated breast milk samples in ELISA (Enzyme-Linked Immunosorbent Assays) experiments and with a home-made laboratory device consisting of a fluidic system containing a biochip inserted into a cartridge. Virus concentrations as low as 6 ng/mL can be detected by this simple opto-fluidic device with a higher absorbance value than the one obtained with ELISA technique. This suggests that lower virus concentrations of virus could be detected with a more sophisticated device. These preliminary experiments open the way to the fabrication of bedside RDT. In conclusion, the blend between medical and engineering research will ensure the translation of VIRUMILK’s findings to the clinics with a ready-to-use HCMV RDT to curtail the important disease burden associated with HCMV infection.

Paper Nr: 6
Title:

Optical Detection of Red Blood Cells Captured on Biochips for RH1 Compatibility Control at the Patient’s Bedside

Authors:

Karine Charrière, Alain Rouleau, Pascal Morel, Audrey Guitton, wilfrid boireau, Lionel Pazart, Véronique Bourcier, Carole Tissot and Bruno Wacogne

Abstract: Every year, several millions of red cell concentrates are transfused. For each of them, a pretransfusional compatibility test is performed. In France, an ABO compatibility test at the patient’s bedside is performed, but rhesus compatibility is not yet checked. However, rhesus antigens are very immunogenic and could lead to Rh incompatibility or Rh disease. Rh incompatibility occurs when a woman with Rh-negative blood type is exposed to Rh-positive blood cells. This exposure leads to the sensitization of the women who develop anti-Rh IgG. This immunization is one cause of the hemolytic disease of newborns (HDN). HDN results from an incompatibility between mother’s blood and fetus’ blood. It happens when fetal red blood cells (RBCs) present antigens inherited from the father but missing from the mother. Consequence of this incompatibility is the fetal RBCs destruction by mother’s antibodies. Antibodies could be natural, like IgM anti-A or anti-B from the ABO system, or from an immunization. Rh incompatibility results from 2 main mechanisms. The first one is when a pregnancy Rh-negative woman is exposed to fetal Rh-positive RBCs. Rh incompatibility leads to anemia (mild to severe) or ultimately to the in utero death. The second occurs when Rh incompatible blood is transfused. This is the subject of this communication. We previously develop biochips and optical device to realize automatic ABO compatibility test at the patient’s bedside (Charrière et al., 2015; Wacogne et al., 2011a, 2011b). Based on this project, we develop another biochip based on selective blood capture. The designed chip specifically captures RBCs according the presence of the RH1 antigen (also known as D antigen) at their surface. The device drives the different fluids and performs optical detection of captured red cells. Here, we recall the biochips fabrication, the control of their efficiency using SPRi methods and we present their integration in the device and the system efficiency in terms of biochips specificity and optical detection limits. Charrière, K., Rouleau, A., Gaiffe, O., Fertey, J., Morel, P., Bourcier, V., Pieralli, C., Boireau, W., Pazart, L., Wacogne, B., 2015. Biochip technology applied to an automated ABO compatibility test at the patient bedside. Sens. Actuators B Chem. 208, 67–74. doi:10.1016/j.snb.2014.10.123 Wacogne, B., Boireau, W., Morel, P., Pazart, L., Pieralli, C., 2011a. Device for taking a sample of a body fluid and method for implementing same. WO 2011/055029. Wacogne, B., Boireau, W., Morel, P., Pazart, L., Pieralli, C., 2011b. Secure perfusion system. WO 2011/0055031.

Paper Nr: 8
Title:

New Frontiers: Improving Long Term Care through Health Information Exchange

Authors:

Rebecca Meehan

Abstract: Health care technology, electronic health records (EHR) in particular, continue to make strides in interoperability, to facilitate opportunities for seamless transfer of patient health information. When a patient is discharged from one care center to another (i.e. from an acute care hospital to a long term care center), clinicians need the best summary of care to maintain patient safety and improve patient health (e.g. being aware of life-threatening allergies). One of the primary methods of sharing health data for a patient from one health setting (e.g. hospital) to another is health information exchange (HIE). HIE is a technological process by which health care providers and stakeholders can electronically access and securely share pertinent medical data. Processes around using HIE are still evolving as many health care providers and hospitals in the United States are using the technology, it is not commonplace, and is not part of typical workflow. This is especially true of long term care (LTC) facilities that, because of financial resources, and lack of eligibility to federal reimbursement programs, have been lagging behind in technology adoption: specifically, EHR and HIE. This study examines the user experience of an HIE data sharing method, and health care staff attitudes on the impact of HIE on patient care. Current HIE models will be discussed, including an innovative hybrid staffing model where clinicians from area hospitals are working onsite at the LTC facility to help improve health outcomes by clarifying health data (e.g. medication lists) and to save money by eliminating redundant procedures/tests, and reducing re-admissions to hospitals.

Paper Nr: 9
Title:

Transmission pathway of human body communication through both skin and the air: Preliminary experiments

Authors:

Jin-Hee Moon, Changyul Cheon, Dong Hyun Baek, Sang-Hoon Lee, Seung-A Lee and Sung-Keun Yoo

Abstract: Human Body Communication (HBC) uses the human body as a communication medium, and is attracting rich attention due to low energy consumption and robustness to interference from adjacent signal. However, the mechanism by which HBC operates is dominantly known to be electrostatic coupling. Zimmerman asserts very small current is induced by electrostatic coupling, and it conducts through body. And he persists that electrodes for HBC do not work as antenna because the length (below 10 cm) is too small to resonate below several hundred MHz. Itao groups have studied on the mechanism and concluded that signal could be distributed as a surface wave on the skin. As their theory, the signal has to travel through the skin either as small current or as surface wave. But we found that much signal power is radiated in the air and is transmitted when the electrode is attached on the body though the size of antenna electrode is too small to radiate the signal of several hundred MHz. We hypothesized these phenomena as antenna effect of human body, and experimental studies were conducted to investigate that HBC is governed by both capacitive coupling and antenna effect of human body. The experimental proof was carried out through the use of human body, and the experimental environment was set to be noise-free. Some types of body communication model revealed that signals are transferred through both the skin and the air using body as antenna, although the skin provides a better transmission medium than air. These results will be useful in the design of more advanced HBC systems.

Paper Nr: 10
Title:

An optimized method enables in vivo imaging of the murine lung without stabilization

Authors:

Daniel Fiole

Abstract: Lung tissue motion arising from breathing and heart beating has been described as the largest annoyance of in vivo imaging. Consequently, infected lung tissue has been only scarcely imaged in vivo thus far, and little is known concerning the kinetics of the mucosal immune system at the cellular level. We have developed an optimized post-processing strategy to overcome tissue motion, based upon two-photon and second harmonic generation (SHG) microscopy. In contrast to previously published data, we have freed the lung parenchyma from any strain and depression in order to maintain the lungs under optimal physiological parameters. Excitation beams swept the sample throughout normal breathing and heart movements, allowing the collection of many images. Given that tissue motion is unpredictably, it was essential to sort images of interest. This step was enhanced by using SHG signal from collagen as a reference for sampling and realignment phases. A normalized cross-correlation criterion was used between a manually chosen reference image and rigid transformations of all others. Using CX3CR1+/gfp mice this process allowed the collection of high resolution images of pulmonary dendritic cells (DCs) interacting with Bacillus anthracis spores, a Gram-positive bacteria responsible for anthrax disease. We imaged lung tissue for up to one hour, without interrupting normal lung physiology. Interestingly, our data revealed unexpected interactions between DCs and macrophages, two specialized phagocytes. These contacts may participate in a better coordinate immune response. This technique allowing microscopic imaging of the living lung without involving any mechanical stabilization of the lung may prove to be of the highest interest for scientists investigating the subtle behaviour of immune cells, which would greatly suffer from any invasive stabilization of the lung.

Paper Nr: 11
Title:

Incorporating Out-of-Pocket Patients Costs into Decision-Support for Prescribing Decisions in Hypertension Management

Authors:

Robyn Tamblyn, Teresa Moraga, Michal Abrahamowicz, Jessica Nadigel and Allen Huang

Abstract: Prescription drugs represent a rapidly growing sector of expenditure. Antihypertensive medication accounts for over 20% of $1.3 trillion annual worldwide expenditures, a cost that could be substantially reduced if there was greater use of diuretics as first line treatment for uncomplicated hypertension. Although physicians are mainly interested in the risk-benefit of their treatment decisions, out-of-pocket costs for patients are an important consideration. With recent advances in computerized drug management systems, it is now possible to provide physicians with feedback, at the time of prescribing, about the patient’s co-payment plan and out-of-pocket payment costs of their treatment decisions. Estimate the impact on treatment decisions of providing feedback to physicians about the additional out-of-pocket payment required for patients started on non-diuretic treatment for uncomplicated hypertension. A cluster randomized trial was conducted in 79 primary care physicians and 3,998 patients treated for uncomplicated hypertension in Quebec, Canada between 2009 and 2015. Physicians using an integrated computerized drug management system were randomized to decision-support on out-of-pocket payment costs, adherence and treatment target monitoring or usual care. GEE logistic regression was used to estimate the impact of the intervention on treatment choice at the first visit post-randomization. In the year before the start of the trial, the mean annual cost of antihypertensive treatment was $370 (control)-$381 (intervention)/ patient, and only 15.5% (intervention) to 19.9% (control) of patients with uncomplicated diuretics were prescribed diuretics. At the first visit post-randomization, 40.9% of patients were newly started on treatment. Among these incident patients, a higher proportion of intervention patients were started on diuretics (26.2% vs 20.7%; p<0.01), whereas there was no difference for prevalent patients [12.6% (for intervention group) vs 12.1% (for control group), p>0.05] . Feedback on out-of-pocket payment results in lower cost evidence-based treatment choices for newly treated patients with uncomplicated hypertension, a difference that would result in an overall national saving of over $1 billion in Canada.

Posters
Paper Nr: 3
Title:

Bio-lead with sciatic nerve or PC12 cells for neural stimulation in rat

Authors:

Seung-A Lee, Jin-Hee Moon, Sung-Keun Yoo, Ha-Chul Jung, Jin-Won Kim, In-ho Song, Seun Woo Bong, Jin Woo Ahn and Dong-Jun Moon

Abstract: When a metal electrode is implanted into the brain or spinal cord, an inflammatory response is initiated. After proceeding the implantation, microglia become activated and migrated to the site of implantation, they are located at next to the electrode interface. After that moment, the reactive astrocytes encapsulate the implanted electrode. Since the encapsulation response increases tissue impedance, it is hard to stimulate from a region of the brain or spinal cord. Also, an implanted electrode occurs an induced current by electromagnetic field so that the generation of induced current increases tissue damage. Therefore, the challenge lies in technological methods to develop the implantable electrode and lead without causing tissue damage, which minimize the disruption of the encapsulation and an inner environment of body. So, those below conditions of the methods strictly meet the qualification; (i) they should have same in vivo conditions as a rat body. (ii) They should be minimized inflammatory response. (iii) They should be improved the performance and stability of stimulation and recording signal. (iv)They should be effective in the long-term communication. In this open communication, we propose the technology procedures and design of a Bio-lead composed of sciatic nerve or PC12 (rat adrenal medulla cell line) cells. Compared with the implantable electrodes that mentioned above, the newly developed Bio-lead will enable stimulate the nerves and brain without tissue encapsulation. We will perform the experiment with a sciatic nerve of rat and PC12 cells is the main to manage an inflammation; a stability of long-term interfaces between electrodes and tissue is the main issue. Assume that a possibility of the procedure is confirmed, an expanded procedure is performed as well. Since the sciatic nerve of rat will able to stimulate other nerves and record neural signals, after harvesting a sciatic nerve from rat and do the experiment the stimulation and measurement tests for other nerves using the nerve taken from a rat instead of a lead electrode. After verification that it can be used as the bio-lead, an artificially produced bio-lead in vivo condition with PC12 cells. First, PC12 cells will be seeded and cultured on the biodegradable tubular scaffold or sheet made by MEMS and macromolecule synthesis techniques. In addition to examining whether bio-lead with PC12 cells is suitable for electrodes, a conventional electrode to bio-lead with PC12 cells will be connected and investigated the efficacy of bio-lead. Also, the procedure will go step by step through an examining cell viability test, an immunocytochemistry, a histological analysis and an electrode characterization. The proposed bio-lead with sciatic nerve or PC12 cells could be applied to studies on investigation of neural prostheses and electrical stimulation therapies. *Bio-lead: bio(tissue or cells)-based lead

Paper Nr: 4
Title:

pH sensitivity comparison between inversion and depletion mode silicon nanowire field-effect transistors (Si-NWFETs) for development of nanobiosensors

Authors:

Sung Keun Yoo, Jin-Won Kim, Ha-Chul Jung, Jin-Hee Moon, In-ho Song, Seung-A Lee and Dong-Jun Moon

Abstract: This paper demonstrates the pH sensitivity comparison results between inversion mode and depletion mode silicon nanowire field-effect transistors (Si-NWFETs). The depletion mode Si-NWFETs showed a much higher sensitivity although the doping level of Si-NW channel was higher than that of inversion mode. The results indicate that the depletion mode Si-NWFETs are more appropriate operation mode to biosensing application, which needs higher sensitivity than pH sensing application. For the fabrication of Si-NWFETs of two different sensing mode, 100 nm-wide and 50 nm-thick, 40 μm-long Si-NW channels were defined on silicon-on-Insulator (SOI) wafers by using electron-beam lithography and microfabrication technologies. The doping level of device layer used for inversion mode Si-NWFETs and depletion mode Si-NWFETs is 1×1015/cm3 and 1×1018/cm3, respectively. Due to the doping level difference in the device layer, Schottky contact was used for the inversion mode Si-NWFETs, on the other hand Ohmic contact was used for the depletion mode Si-NWFETs for formation of source and drain. The time-dependent responses to the variation of pH level were observed and the ratios of current variation (IpH10/IpH4 or IpH4/IpH10) were calculated for the sensitivity comparison. The current variation ratio of an inversion mode Si-NWFET and depletion mode one is 2.4 and 16.25, respectively. The high ratio indicates that the depletion mode Si-NWFETs are more sensitive to the charge variation on the surface of Si-NW thereby sensitive sensing to the attachment of charged biomolecules. We further studied the pH sensing characteristics of the depletion mode Si-NWFET. The sensor was able to detect 0.5 pH unit change stably in the range between pH 5.0 to pH 9.0, and showed good repeatability with value lesser than 10% of coefficient of variation.