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Radiotherapy (RT) is currently only used in children with high-risk neuroblastoma (NB) due to concerns of long-term side effects as well as lack of effective adjuvant. Calreticulin (CALR) has served distinct physiological roles in cancer malignancies; nonetheless, impact of radiation on chaperones and molecular roles they play remains largely unknown. In present study, we systemically analyzed correlation between CALR and NB cells of different malignancies to investigate potential role of CALR in mediating radioresistance of NB. Our data revealed that more malignant NB cells are correlated to lower CALR expression, greater radioresistance, and elevated stemness as indicated by colony- and neurospheroid-forming abilities and vice versa. Of note, manipulating CALR expression in NB cells of varying endogenous CALR expression manifested changes in not only stemness but also radioresistant properties of those NB cells. Further, CALR overexpression resulted in greatly enhanced ROS and led to increased secretion of proinflammatory cytokines. Importantly, growth of NB tumors was significantly hampered by CALR overexpression and was synergistically ablated when RT was also administered. Collectively, our current study unraveled a new notion of utilizing CALR expression in malignant NB to diminish cancer stemness and mitigate radioresistance to achieve favorable therapeutic outcome for NB.

Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote cross-species transmission and the rapid evolution of microbes in emerging diseases. In addition, natural surface structures with unique anti-biofouling properties may be used as guide templates for the development of functional antimicrobial surfaces. Further, these structure-related antimicrobial surfaces can be categorized into microbicidal and anti-biofouling surfaces. This review introduces the recent advances in the development of microbicidal and anti-biofouling surfaces inspired by natural structures and discusses the related antimicrobial mechanisms, surface topography design, material application, manufacturing techniques, and antimicrobial efficiencies.

Flexible neural probes have been pursued previously to minimize the mechanical mismatch between soft neural tissues and implants and thereby improve long-term performance. However, difficulties with insertion of such probes deep into the brain severely restricts their utility. We describe a solution to this problem using gallium (Ga) in probe construction, taking advantage of the solid-to-liquid phase change of the metal at body temperature and probe shape deformation to provide temperature-dependent control of stiffness over 5 orders of magnitude. Probes in the stiff state were successfully inserted 2 cm-deep into agarose gel “brain phantoms” and into rat brains under cooled conditions where, upon Ga melting, they became ultra soft, flexible, and stretchable in all directions. The current 30 μm-thick probes incorporated multilayer, deformable microfluidic channels for chemical agent delivery, electrical interconnects through Ga wires, and high-performance electrochemical glutamate sensing. These PDMS-based microprobes of ultra-large tunable stiffness (ULTS) should serve as an attractive platform for multifunctional chronic neural implants.

With the limited sample volume, the droplet-based microfluidic becomes attractive in biomedical diagnosis, especially for measuring multiple analytes. Usually, for multiplexing by parallel processing, a larger sample volume is required. In our previous study, simultaneously detecting two analytes from a single droplet was first achieved by measuring different fluorescence wavelengths for different analytes. However, the number of detectable analytes could be limited by the spectral resolution of fluorescence. Here a different approach is proposed for multiplexing by sharing a single droplet in multiple sub-assays. Therefore, only a single-type reporter, i.e., the fluorescence with the same wavelength, is needed for detection of different analytes from a single sample droplet, called single-type reporter multiplexing (STRM). The standard curves of two analytes, human IL-1β and human TNF-α, are demonstrated. The required sample volume for one measurement is only 520 nL; the total duration of the on-chip process is less than 50 min. The limits of detection (LOD) of human IL-1β and human TNF-α are about 1.14 and 0.97 pg/mL, respectively. It is shown that the proposed bead-based digital microfluidic immunoassay can achieve multiple analytes detection with low LOD from a single sample droplet using the single-type reporter, which has never been achieved before.

Fouling causes numerous adverse effects on various types of systems. In addition, clean fouling on a solid surface is cost-intensive and time-consuming. Superhydrophobic (SHB) surfaces with a water-repellent property can potentially be used for antifouling. However, SHB surfaces lose their antifouling property at high temperatures because of the failure of the hydrophobic coating on them. Nevertheless, there are numerous applications being operated at high temperatures. Thus, a surface exhibiting antifouling characteristic over a wide temperature range is required. In this study, we demonstrate that a double re-entrant pillar (DRP) array surface possesses a wide-temperature antifouling characteristic. Although the silicon dioxide top surface of the pillar is hydrophilic, the upward surface tension force from the DRPs prevents the impacting droplets from penetrating the pillar array. Thus, the impacting droplets bounce back from the surface without leaving residues on it at temperatures from 25 to 560°C. By contrast, the impurities of the impacting droplets are retained on an SHB surface composed of a silicon nanowire array at various temperatures. The wide-temperature antifouling property of the DRP surface can be used for preventing fouling in many industrial systems.

Dilution is a common procedure in biological and chemical analyses to perform tests at different concentrations. In previously reported micro diluters, although they could provide a wide dilution range, only limited dilution ratios were demonstrated, i.e. low flexibility in dilution ratio. Here, a droplet-based micro diluter with high flexibility on dilution ratio is proposed, fabricated, and tested. Through combination of five different electrode sizes using electrowetting-on-dielectric (EWOD) technique, the proposed micro diluter can provide 49 dilution ratios at dilution range from 1/2 to 1/50. Experimental results verify that different dilution ratios can be successfully generated, even at the most difficult low concentration range. Comparing to the design with equal electrode size in conventional EWOD-based microfluidic chip, the proposed design with unequal electrode sizes can reduce the operation steps to achieve high flexibility on dilution ratios efficiently.

A fall-down recorder can record the happening of an object falling down during object delivery or transportation, even after the object is recovered to its initial state. Here, a resettable, wireless and passive fall-down recorder is proposed by integrating a droplet-based inertial force switch with the inductor–capacitor ( $LC$ ) circuit for wireless signal transmission. A magnetic droplet is used in the switch with a converging microchannel to control the desired threshold acceleration. When the inertial force exceeds the designed threshold acceleration, the magnetic droplet will pass through the converging microchannel to a deep cavity to become a different state. By connecting the switch with the sensing $LC$ circuit, the state of the recorder can be wirelessly identified through the $LC$ resonant frequency. After triggering, this switch can be remotely reset to its initial state by an external magnet. A proper hydrophobic surface treatment is employed to facilitate the movement of the magnetic droplet and reduce the variation on the threshold acceleration. The capabilities, including switching, recording, wireless reading, and resetting of the proposed fall-down recorder, are successfully designed, fabricated, and verified with ten recording-reset tests.

An implantable system for drug delivery provides a new strategy for drug therapy, and typically involves a microfluidic chip produced with micro or nano-technology. Implantable systems have the flexibility to conform various schemes of drug release, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Such an implantable system is classified as allowing either controllable or uncontrollable drug release after implantation, so an active or passive delivery system respectively. The performance and related applications of these systems vary. The key points of each technology are highlighted such as performance, working principle, fabrication methods, and dimensional constrains. We here review the implantable drug-delivery system in current research with a focus on application and chip performance, and comparison for passive and active delivery system.

One of the challenges in IVF treatment is to improve the pregnancy rate of selective single embryo implantation. The concentration of IL-1β in embryo culture medium may help to predict pregnancy rate. Clinically, each embryo can only get small amount of sample size. However, the traditional immunoassay cannot detect biomarkers in such small sample sizes. Therefore, we combined immunoassay with the bead-based digital microfluidic chip. The chip has two advantages, low sample requirement and low detection limit. We established the mouse IL-1β calibration curve, confirm the Human Tubal Fluid (HTF) does not influence the test result and demonstrate that mouse IL-1β in clinical mouse embryo culture medium is positively correlate to cultured days. This device has a great potential for increasing IVF pregnancy rates.

From traditional manufacturing to integrated circuit technology, shaft components have been utilized in different kinds of industries. Therefore, torsion monitoring to maintain the precision of machines is an important task. However, in order to check the performance, the shaft component needs to be dismounted from working position and installed in an expensive testing system for further diagnoses, which is labor-consuming and inefficient. In this study, we proposed a passive, wireless smart LC sensing tag based on the developed LC technology produced by commercial aluminum foil lamination and fast slitting techniques. With this smart tag fixed on the shaft, the torque generated by the system can be monitored, since the resonance frequency, shifting accordingly to the change of torque, can be readable by RF coils' inducting. Therefore, the smart LC sensing tag can work wirelessly and passively without physically connecting to a battery or power module. The goal of this study is to monitor stress at least 0.0056e by using the portable antenna analyzer which has the resolution about 1.3113MHz/e. This technology has the great vision that applies to the shaft monitoring in vehicles or fabrication machines. Furthermore, it can be integrated into IOT application.

A novel approach which uses a multiple partial exposure method to fabricate a transparent structured superomniphobic surface with doubly re-entrant structures by using negative thick photoresist SU-8 as the material is proposed. By using gray-tone lithography, the doubly re-entrant structures can be formed only via a standard lithography process. The gray-tone lithography for fabricating the doubly re-entrant structures is achieved by depositing three appropriate thicknesses of Ti film on glass substrate that acts as the gray-tone mask. The proposed transparent surface with the doubly re-entrant structures successful suspend all the tested liquid even the completely wetting liquid, such as silicon oil with the surface tension of 20.9 mN/m. This approach provides a simple, flexible and low-cost solution for fabricating superomniphobic surface, and it also has the potential to integrate with either flexible or nonflexible substrate for different applications.

Interlocking nailing is a common surgical operation to stabilize fractures in long bones. One of the difficult parts of the surgery is how to locate the position and direction of a screw hole on the interlocking nail, which is invisible to the naked eye after insertion of the nail into the medullary canal. Here, we propose a novel two-stage targeting process using two passive magnetic devices to locate the position and direction of the screw hole without radiation for the locking screw procedure. This involves a ring-shape positioning magnet inside the nail to generate a magnetic field for targeting. From the accuracy test results of these two-stage targeting devices, the search region can be identified in less than 20 seconds by the 1st-stage targeting device, while the total targeting time to locate the drilling position and direction takes less than 4 minutes, with 100% successful rate in 50 attempts. The drilling test further combines the two-stage targeting process and drilling process on the swine tibia, and it is shown that a 100% successful rate is achieved in all 10 attempts, where the total time needed is less than 5 minutes.

At present, intramedullary interlocking nails are widely used for bone-fracture fixation in orthopedic surgeries. Surgeons often use X-ray imaging to find the actual location of the distal screw-holes of the nail after the nail is inserted into the medullary canal of a bone for fixation. Thus, the patients and medical team are inevitably exposed to radioactivity. In this paper, we report a radiation-free electromagnetic/magnetic- coupled targeting system to locate the distal screw-holes of the nail used in interlocking-nail surgery. The targeting system consists of a c-shaped electromagnet with a pick-up coil, a highly permeable curved silicon-steel strip embedded on the nail, a guiding mechanism, and electronic measuring instruments. An alternative current is applied to the electromagnet to generate a uniform magnetic field/flux in the electromagnet's air gap. When the nail inserted into the medullary canal of a bone is scanned through or rotated in the air gap of the electromagnet, the magnetic flux in the air gap is influenced by the silicon-steel strip embedded on the nail. The variation of the magnetic flux induces a voltage response in the pick-up coil due to electromagnetic induction. The pattern of the voltage response is analyzed to establish a criterion for screw-hole targeting. The results obtained using this criterion reveal that the maximum targeting error of the location and orientation targeting for a screw-hole with a diameter of 5 mm is

We report an electromagnetic inductance/coil-based non-destructive method to target distal screw-holes in an intramedullary interlocking-nail surgical operation for fixing a long-bone fracture. The method is a radiation-free approach addressing the over-exposure issue of radioactivity caused by the typical X-ray-imaging approach. According to the method, we fabricate a targeting-system consisting of an internal inductance, external coil, guiding-mechanism, and driving/measurement electronics. When a voltage is applied to the internal inductance embedded in one of the distal screw-holes of a nail inserted in a bone, a directional magnetic flux is generated by the internal inductance due to the electromagnetic induction. Subsequently, the directional magnetic flux penetrates the nail and bone. When the external coil outside the bone scans along the axial and angular directions of the nail/bone, different amount of the generated magnetic flux is detected by the coil and consequently corresponding voltage response is induced in the coil due to the electromagnetic induction. In contrast to the magnetic flux generated and detected by the inductance and coil, respectively, we also investigate the reverse physics-behavior of the flux transmission (i.e., flux generated and detected by the coil and inductance) in order to improve the approach. Finally, by correlating the induced-voltage responses with the scanned axial-locations along the nail/bone, correlation curves are plotted. Through analyzing the curves, a criterion for predicting the location of the screw-holes of the nail is established. When compared the predicted location with the actual location of the screw-hole, the maximum targeting error is 2 mm for locating a screw-hole with a diameter of 5 mm. The result shows the targeting-method is accurate, fast, and easy for the surgeons and significantly simplifies the existed interlocking-nail surgical procedures.

This paper presents the prototype of a new remote guiding device to find the accurate screw hole position for drilling and direction for locking in intramedullary nailing surgery. The device consists of three magnetic pins and an electrical conductive board. The three symmetrically placed magnetic pins can rotate freely and point to the permanent magnet inside the nail. The drilling position and screwing direction can be obtained by moving the device with those magnetic pins to align with the magnet in the nail. The alignment condition is indicated by a LED. When the device is not aligned with the magnet in the nail properly, either in position or direction, the pins then will contact with the board to trigger a light-emitting diode for alarming.

We report a novel approach for targeting screw-holes of an intramedullary nail in a long-bone fracture surgery. The approach utilizes the electromagnetic induction to avoid over exposure of radioactivity which is the critical issue in conventional X-ray-imaging targeting method. Based on the approach, we fabricate a targeting system. The targeting system consists of a c-shaped electromagnet, detecting-coil, guiding-mechanism, and measurement electronics. When a voltage is applied to the electromagnet, magnetic flux is generated in the air gap of the electromagnet and subsequently detected by the coil. When the flux is detected by the coil, a voltage response is induced in the coil. When a nail in a bone is scanned through the air gap of the electromagnet, the flux is influenced due to a discrepancy of the permeability between the location with and without the hole of the nail. The influenced flux induces different voltage response in the coil. Through analyzing the voltage response, we establish a criterion for targeting the holes. By the criterion, the experimental result shows the maximum error of targeting a hole with a diameter of 5 mm is less than 2.5 mm.