Takayuki Arie

Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin

Sickle trait, the heterozygous state of normal hemoglobin A (HbA) and sickle hemoglobin S (HbS), confers protection against malaria in Africa. AS children infected with Plasmodium falciparum are less likely than AA children to suffer the symptoms or severe manifestations of malaria, and they often carry lower parasite densities than AA children. The mechanisms by which sickle trait might confer such malaria protection remain unclear. We have compared the cytoadherence properties of parasitized AS and AA erythrocytes, because it is by these properties that parasitized erythrocytes can sequester in postcapillary microvessels of critical tissues such as the brain and cause the life-threatening complications of malaria. Our results show that the binding of parasitized AS erythrocytes to microvascular endothelial cells and blood monocytes is significantly reduced relative to the binding of parasitized AA erythrocytes. Reduced binding correlates with the altered display of P. falciparum erythrocyte membrane protein-1 (PfEMP-1), the parasites major cytoadherence ligand and virulence factor on the erythrocyte surface. These findings identify a mechanism of protection for HbS that has features in common with that of hemoglobin C (HbC). Coinherited hemoglobin polymorphisms and naturally acquired antibodies to PfEMP-1 may influence the degree of malaria protection in AS children by further weakening cytoadherence interactions.

α-Thalassemia impairs the cytoadherence of Plasmodium falciparum-infected erythrocytes.

Background α-thalassemia results from decreased production of α-globin chains that make up part of hemoglobin tetramers (Hb; α2β2) and affects up to 50% of individuals in some regions of sub-Saharan Africa. Heterozygous (−α/αα) and homozygous (−α/−α) genotypes are associated with reduced risk of severe Plasmodium falciparum malaria, but the mechanism of this protection remains obscure. We hypothesized that α-thalassemia impairs the adherence of parasitized red blood cells (RBCs) to microvascular endothelial cells (MVECs) and monocytes – two interactions that are centrally involved in the pathogenesis of severe disease. Methods and Findings We obtained P. falciparum isolates directly from Malian children with malaria and used them to infect αα/αα (normal), −α/αα and −α/−α RBCs. We also used laboratory-adapted P. falciparum clones to infect −/−α RBCs obtained from patients with HbH disease. Following a single cycle of parasite invasion and maturation to the trophozoite stage, we tested the ability of parasitized RBCs to bind MVECs and monocytes. Compared to parasitized αα/αα RBCs, we found that parasitized −α/αα, −α/−α and −/−α RBCs showed, respectively, 22%, 43% and 63% reductions in binding to MVECs and 13%, 33% and 63% reductions in binding to monocytes. α-thalassemia was associated with abnormal display of P. falciparum erythrocyte membrane protein 1 (PfEMP1), the parasite’s main cytoadherence ligand and virulence factor, on the surface of parasitized RBCs. Conclusions Parasitized α-thalassemic RBCs show PfEMP1 display abnormalities that are reminiscent of those on the surface of parasitized sickle HbS and HbC RBCs. Our data suggest a model of malaria protection in which α-thalassemia ameliorates the pro-inflammatory effects of cytoadherence. Our findings also raise the possibility that other unstable hemoglobins such as HbE and unpaired α-globin chains (in the case of β-thalassemia) protect against life-threatening malaria by a similar mechanism.

Fully Printed, Highly Sensitive Multifunctional Artificial Electronic Whisker Arrays Integrated with Strain and Temperature Sensors

Mammalian-mimicking functional electrical devices have tremendous potential in robotics, wearable and health monitoring systems, and human interfaces. The keys to achieve these devices are (1) highly sensitive sensors, (2) economically fabricated macroscale devices on flexible substrates, and (3) multifunctions beyond mammalian functions. Although highly sensitive artificial electronic devices have been reported, none have been fabricated using cost-effective macroscale printing methods and demonstrate multifunctionalities of artificial electronics. Herein we report fully printed high-sensitivity multifunctional artificial electronic whiskers (e-whisker) integrated with strain and temperature sensors using printable nanocomposite inks. Importantly, changing the composition ratio tunes the sensitivity of strain. Additionally, the printed temperature sensor array can be incorporated with the strain sensor array beyond mammalian whisker functionalities. The sensitivity for the strain sensor is impressively high (∼59%/Pa), which is the best sensitivity reported to date (>7× improvement). As the proof-of-concept for a truly printable multifunctional artificial e-whisker array, two- and three-dimensional space and temperature distribution mapping are demonstrated. This fully printable flexible sensor array should be applicable to a wide range of low-cost macroscale electrical applications.

Fully Printed Flexible Fingerprint-like Three-Axis Tactile and Slip Force and Temperature Sensors for Artificial Skin

A three-axis tactile force sensor that determines the touch and slip/friction force may advance artificial skin and robotic applications by fully imitating human skin. The ability to detect slip/friction and tactile forces simultaneously allows unknown objects to be held in robotic applications. However, the functionalities of flexible devices have been limited to a tactile force in one direction due to difficulties fabricating devices on flexible substrates. Here we demonstrate a fully printed fingerprint-like three-axis tactile force and temperature sensor for artificial skin applications. To achieve economic macroscale devices, these sensors are fabricated and integrated using only printing methods. Strain engineering enables the strain distribution to be detected upon applying a slip/friction force. By reading the strain difference at four integrated force sensors for a pixel, both the tactile and slip/friction forces can be analyzed simultaneously. As a proof of concept, the high sensitivity and selectivity for both force and temperature are demonstrated using a 3×3 array artificial skin that senses tactile, slip/friction, and temperature. Multifunctional sensing components for a flexible device are important advances for both practical applications and basic research in flexible electronics.

Toward Flexible and Wearable Human‐Interactive Health‐Monitoring Devices

This Progress Report introduces flexible wearable health-monitoring devices that interact with a person by detecting from and stimulating the body. Interactive health-monitoring devices should be highly flexible and attach to the body without awareness like a bandage. This type of wearable health-monitoring device will realize a new class of electronics, which will be applicable not only to health monitoring, but also to other electrical devices. However, to realize wearable health-monitoring devices, many obstacles must be overcome to economically form the active electrical components on a flexible substrate using macroscale fabrication processes. In particular, health-monitoring sensors and curing functions need to be integrated. Here recent developments and advancements toward flexible health-monitoring devices are presented, including conceptual designs of human-interactive devices.

Carbon-nanotube probe equipped magnetic force microscope

Metal capped carbon nanotubes, prepared by catalytic decomposition of benzene, have been applied as a magnetic force microscope tip. The particles at the end of nanotubes were about 35 nm in diameter, which were found to be Ni3C from the electron diffraction pattern. The other end of the nanotubes was attached on the tip of conventional Si probes. The magnetization of the particles was carried out parallel to the nanotube axis by applying a pulsed magnetic field of 12.5 T. We demonstrate the performance of these carbon nanotube probes by imaging the stored signal in magnetic recording media with magnetic force microscopy.

Carbon Nanotube Resonator in Liquid

To achieve mass measurement of biological molecules in viscous fluids using carbon nanotube resonators, we investigated the vibration of nanotube cantilevers in water using the optical detection technique. In vacuum, we often found a few resonance modes of nanotube vibrations. However, the nanotube lost its fundamental oscillation once immersed in water, suggesting a great viscous resistance to the nanotube vibration in water. The resonant frequency of the nanotube in water decreased with lowering the water temperature, corresponding to the natural phenomenon by which liquid viscosity tends to increase at lower temperatures.

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

Background In Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF) and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs). A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified. Methods and Findings We found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB) RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs), monocytes, and nonparasitized RBCs – cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasites cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1) on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs. Conclusions Our data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infants contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood.

Highly selective flexible tactile strain and temperature sensors against substrate bending for an artificial skin

Flexible devices can conformally cover any surfaces and interact with different stimuli such as human touch. Although a flexible tactile sensor has been reported as an artificial skin application, distinguishing between a tactile force and strain due to substrate bending remains challenging. Here we report a highly selective tactile force sensor against bending on the basis of strain engineering by fabricating a cantilever structure. The proposed device achieves a 4–23 times improvement in selectivity compared to conventional pressure sensitive rubber. As a proof-of-concept for e-skin, an array composed of highly selective tactile force sensors and temperature sensors is successfully demonstrated to imitate human skin.

Printed multifunctional flexible device with an integrated motion sensor for health care monitoring

Printable, multifunctional, flexible, health monitoring detachable patch sheets with human motion detection capability. Real-time health care monitoring may enable prediction and prevention of disease or improve treatment by diagnosing illnesses in the early stages. Wearable, comfortable, sensing devices are required to allow continuous monitoring of a person’s health; other important considerations for this technology are device flexibility, low-cost components and processing, and multifunctionality. To address these criteria, we present a flexible, multifunctional printed health care sensor equipped with a three-axis acceleration sensor to monitor physical movement and motion. Because the device is designed to be attached directly onto the skin, it has a modular design with two detachable components: One device component is nondisposable, whereas the other one is disposable and designed to be worn in contact with the skin. The design of this disposable sensing sheet takes into account hygiene concerns and low-cost materials and fabrication methods as well as features integrated, printed sensors to monitor for temperature, acceleration, electrocardiograms, and a kirigami structure, which allows for stretching on skin. The reusable component of the device contains more expensive device components, features an ultraviolet light sensor that is controlled by carbon nanotube thin-film transistors, and has a mechanically flexible and stable liquid metal contact for connection to the disposable sensing sheet. After characterizing the electrical properties of the transistors and flexible sensors, we demonstrate a proof-of-concept device that is capable of health care monitoring combined with detection of physical activity, showing that this device provides an excellent platform for the development of commercially viable, wearable health care monitors.