Microfluidically Cryo-Cooled Planar Coils for Magnetic Resonance Imaging

High signal-to-noise ratio (SNR) is typically required for higher resolution and faster speed in magnetic resonance imaging (MRI). Planar microcoils as receiver probes in MRI systems offer the potential to be configured into array elements for fast imaging as well as to enable the imaging of extremely small objects. Microcoils, however, are thermal noise dominant and suffer limited SNR. Cryo-cooling for the microcoils can reduce the thermal noise, however conventional cryostats are not optimum for the microcoils because they typically use a thick vacuum gap to keep samples to be imaged to near room temperature during cryo-cooling. This vacuum gap is typically larger than the most sensitive region of the microcoils that defines the imaging depth, which is approximately the same as the diameters of the microcoils. Here microfluidic technology is utilized to locally cryo-cool the microcoils and minimize the thermal isolation gap so that the imaging surface is within the imaging depth of the microcoils. The first system consists of a planar microcoil with microfluidically cryo-cooling channels, a thin N2 gap and an imaging. The microcoil was locally cryo-cooled while maintaining the sample above 8°C. MR images using a 4.7 Tesla MRI system shows an average SNR enhancement of 1.47 fold. Second, the system has been further developed into a cryo-cooled microcoil system with inductive coupling to cryo-cool both the microcoil and the on-chip microfabricated resonating capacitor to further improve the Q improvement. Here inductive coupling was used to eliminate the physical connection between the microcoil and the tuning network so that a single cryocooling microfluidic channel could enclose both the microcoil and the capacitor with minimum loss in cooling capacity. Q improvement was 2.6 fold compared to a conventional microcoil with high-Q varactors and transmission line connection. Microfluidically tunable capacitors with the 653% tunability and Q of 1.3 fold higher compared to a conventional varactor have been developed and demonstrated as matching/tuning networks as a proof of concept. These developed microfluidically cryo-cooling system and tunable capacitors for improving SNR will potentially allow MR microcoils to have high-resolution images over small samples

A Microchip for High-throughput Axon Growth Drug Screening

It has been recently known that not only the presence of inhibitory molecules associated with myelin but also the reduced growth capability of the axons limit mature central nervous system (CNS) axonal regeneration after injury. Conventional axon growth studies are typically conducted using multi-well cell culture plates that are very difficult to use for investigating localized effects of drugs and limited to low throughput. Unfortunately, there is currently no other in vitro tool that allows investigating localized axonal responses to biomolecules in high-throughput for screening potential drugs that might promote axonal growth. We have developed a compartmentalized neuron culture platform enabling localized biomolecular treatments in parallel to axons that are physically and fluidically isolated from their neuronal somata. The 24 axon compartments in the developed platform are designed to perform four sets of six different localized biomolecular treatments simultaneously on a single device. In addition, the novel microfluidic configuration allows culture medium of 24 axon compartments to be replenished altogether by a single aspiration process, making high-throughput drug screening a reality

Development of a Real-Time Microchip PCR System for Portable Plant Disease Diagnosis

Rapid and accurate detection of plant pathogens in the field is crucial to prevent the proliferation of infected crops. Polymerase chain reaction (PCR) process is the most reliable and accepted method for plant pathogen diagnosis, however current conventional PCR machines are not portable and require additional post-processing steps to detect the amplified DNA (amplicon) of pathogens. Real-time PCR can directly quantify the amplicon during the DNA amplification without the need for post processing, thus more suitable for field operations, however still takes time and require large instruments that are costly and not portable. Microchip PCR systems have emerged in the past decade to miniaturize conventional PCR systems and to reduce operation time and cost. Real-time microchip PCR systems have also emerged, but unfortunately all reported portable real-time microchip PCR systems require various auxiliary instruments. Here we present a stand-alone real-time microchip PCR system composed of a PCR reaction chamber microchip with integrated thin-film heater, a compact fluorescence detector to detect amplified DNA, a microcontroller to control the entire thermocycling operation with data acquisition capability, and a battery. The entire system is 25 × 16 × 8 cm(3) in size and 843 g in weight. The disposable microchip requires only 8-µl sample volume and a single PCR run consumes 110 mAh of power. A DNA extraction protocol, notably without the use of liquid nitrogen, chemicals, and other large lab equipment, was developed for field operations. The developed real-time microchip PCR system and the DNA extraction protocol were used to successfully detect six different fungal and bacterial plant pathogens with 100% success rate to a detection limit of 5 ng/8 µl sample

Development and Optimization of Silicon−Dioxide−Coated Capacitive Electrode for Ambulatory ECG Measurement System

This paper presents a silicon−dioxide−coated capacitive electrode system for an ambulatory electrocardiogram (ECG). The electrode was coated with a nano−leveled (287 nm) silicon dioxide layer which has a very high resistance of over 200 MΩ. Due to this high resistance, the electrode can be defined as only a capacitor without a resistive characteristic. This distinct capacitive characteristic of the electrode brings a simplified circuit analysis to achieve the development of a high−quality ambulatory ECG system. The 240 um thickness electrode was composed of a stainless−steel sheet layer for sensing, a polyimide electrical insulation layer, and a copper sheet connected with the ground to block any electrical noises generated from the back side of the structure. Six different diameter electrodes were prepared to optimize ECG signals in ambulatory environment, such as the amplitude of the QRS complex, amplitude of electromagnetic interference (EMI), and baseline wandering of the ECG signals. By combining the experimental results, optimal ambulatory ECG signals were obtained with electrodes that have a diameter from 1 to 3 cm. Moreover, we achieved high−quality ECG signals in a sweating simulation environment with 2 cm electrodes

Implantable Bladder Sensors: A Methodological Review

The loss of urinary bladder control/sensation, also known as urinary incontinence (UI), is a common clinical problem in autistic children, diabetics, and the elderly. UI not only causes discomfort for patients but may also lead to kidney failure, infections, and even death. The increase of bladder urine volume/pressure above normal ranges without sensation of UI patients necessitates the need for bladder sensors. Currently, a catheter-based sensor is introduced directly through the urethra into the bladder to measure pressure variations. Unfortunately, this method is inaccurate because measurement is affected by disturbances in catheter lines as well as delays in response time owing to the inertia of urine inside the bladder. Moreover, this technique can cause infection during prolonged use; hence, it is only suitable for short-term measurement. Development of discrete wireless implantable sensors to measure bladder volume/pressure would allow for long-term monitoring within the bladder, while maintaining the patient’s quality of life. With the recent advances in microfabrication, the size of implantable bladder sensors has been significantly reduced. However, microfabricated sensors face hostility from the bladder environment and require surgical intervention for implantation inside the bladder. Here, we explore the various types of implantable bladder sensors and current efforts to solve issues like hermeticity, biocompatibility, drift, telemetry, power, and compatibility issues with popular imaging tools such as computed tomography and magnetic resonance imaging. We also discuss some possible improvements/emerging trends in the design of an implantable bladder sensor

Development of Real-Time Cuffless Blood Pressure Measurement Systems with ECG Electrodes and a Microphone Using Pulse Transit Time (PTT)

Research has shown that pulse transit time (PTT), which is the time delay between the electrocardiogram (ECG) signal and the signal from a photoplethysmogram (PPG) sensor, can be used to estimate systolic blood pressure (SBP) and diastolic blood pressure (DBP) without the need for a cuff. However, the LED of the PPG sensor requires the precise adjustment of both light intensity and light absorption rates according to the contact status of the light-receiving element. This results in the need for regular calibration. In this study, we propose a cuffless blood pressure monitor that measures real-time blood pressure using a microphone instead of a PPG sensor. The blood pulse wave is measured in the radial artery of the wrist using a microphone that can directly measure the sound generated by a body rather than sending energy inside the body and receiving a returning signal. Our blood pressure monitor uses the PTT between the R-peak of the ECG signal and two feature points of the blood pulse wave in the radial artery of the wrist. ECG electrodes and circuits were fabricated, and a commercial microelectromechanical system (MEMS) microphone was used as the microphone to measure blood pulses. The peak points of the blood pulse from the microphone were clear, so the estimated SBP and DBP could be obtained from each ECG pulse in real time, and the resulting estimations were similar to those made by a commercial cuff blood pressure monitor. Since neither the ECG electrodes nor the microphone requires calibration over time, the real-time cuffless blood pressure monitor does not require calibration. Using the developed device, blood pressure was measured three times daily for five days, and the mean absolute error (MAE) and standard deviation (SD) of the SBP and DBP were found to be 2.72 ± 3.42 mmHg and 2.29 ± 3.53 mmHg, respectively. As a preliminary study for proof-of-concept, these results were obtained from one subject. The next step will be a pilot study on a large number of subjects

Bonding Strength of a Glass Microfluidic Device Fabricated by Femtosecond Laser Micromachining and Direct Welding

We present a rapid and highly reliable glass (fused silica) microfluidic device fabrication process using various laser processes, including maskless microchannel formation and packaging. Femtosecond laser assisted selective etching was adopted to pattern microfluidic channels on a glass substrate and direct welding was applied for local melting of the glass interface in the vicinity of the microchannels. To pattern channels, a pulse energy of 10 μJ was used with a scanning speed of 100 mm/s at a pulse repetition rate of 500 kHz. After 20⁻30 min of etching in hydrofluoric acid (HF), the glass was welded with a pulse energy of 2.7 μJ and a speed of 20 mm/s. The developed process was as simple as drawing, but powerful enough to reduce the entire production time to an hour. To investigate the welding strength of the fabricated glass device, we increased the hydraulic pressure inside the microchannel of the glass device integrated into a custom-built pressure measurement system and monitored the internal pressure. The glass device showed extremely reliable bonding by enduring internal pressure up to at least 1.4 MPa without any leakage or breakage. The measured pressure is 3.5-fold higher than the maximum internal pressure of the conventional polydimethylsiloxane (PDMS)⁻glass or PDMS⁻PDMS bonding. The demonstrated laser process can be applied to produce a new class of glass devices with reliability in a high pressure environment, which cannot be achieved by PDMS devices or ultraviolet (UV) glued glass devices

A Thermocycler Using a Chip Resistor Heater and a Glass Microchip for a Portable and Rapid Microchip-Based PCR Device

This study proposes a rapid and inexpensive thermocycler that enables rapid heating of samples using a thin glass chip and a cheap chip resistor to overcome the on-site diagnostic limitations of polymerase chain reaction (PCR). Microchip PCR devices have emerged to miniaturize conventional PCR systems and reduce operation time and cost. In general, PCR microchips require a thin-film heater fabricated through a semiconductor process, which is a complicated process, resulting in high costs. Therefore, this investigation substituted a general chip resistor for a thin-film heater. The proposed thermocycler consists of a compact glass microchip of 12.5 mm × 12.5 mm × 2 mm that could hold a 2 μL PCR sample and a surface-mounted chip resistor of 6432 size (6.4 mm × 3.2 mm). Improving heat transfer from the chip resistor heater to the PCR reaction chamber in the microchip was accomplished via the design and fabrication of a three-dimensional chip structure using selective laser-induced etching, a rapid prototyping technique that allowed to be embedded. The fabricated PCR microchip was combined with a thermistor temperature sensor, a blower fan, and a microcontroller. The assembled thermocycler could heat the sample at a maximum rate of 28.8 °C/s per second. When compared with a commercially available PCR apparatus running the same PCR protocol, the total PCR operating time with a DNA sample was reduced by about 20%

A portable and high-sensitivity optical sensing system for detecting fluorescently labeled enterohaemorrhagic Escherichia coli Shiga toxin 2B-subunit.

We developed a stand-alone, real-time optical detection device capable of reading fluorescence intensities from cell samples with high sensitivity and precision, for use as a portable fluorescent sensor for sensing fluorescently labeled enterohemorrhagic Escherichia coli (EHEC) Shiga toxins (Stxs). In general, the signal intensity from the fluorescently labeled Stxs was weak due to the small number of molecules bound to each cell. To address this technical challenge, we used a highly sensitive light detector (photomultiplier tube: PMT) to measure fluorescence, and designed a portable optical housing to align optical parts precisely; the housing itself was fabricated on a 3D printer. In addition, an electric circuit that amplified PMT output was designed and integrated into the system. The system shows the toxin concentration in the sample on a liquid crystal display (LCD), and a microcontroller circuit is used to read PMT output, process data, and display results. In contrast to other portable fluorescent detectors, the system works alone, without any peripheral computer or additional apparatus; its total size is about 17 × 13 × 9 cm3, and it weighs about 770 g. The detection limit was 0.01 ppm of Alexa Fluor 488 in PBS, which is ten thousand times lower than those of other smartphone-based systems and sufficiently sensitive for use with a portable optical detector. We used the portable real-time optical sensing system to detect Alexa Fluor 488-tagged Stx2B-subunits bound to monocytic THP-1 cells expressing the toxin receptor globotriaosylceramide (Gb3). The device did not detect a signal from Gb3-negative PD36 cells, indicating that it was capable of specifically detecting Stxs bound to cells expressing the toxin receptor. Following the development of a rapid and autonomous method for fluorescently tagging cells in food samples, the optical detection system described here could be used for direct detection of Shiga toxins in food in the field