Single-shot multi-channel plasmonic real-time polymerase chain reaction for multi-target point-of-care testing.

Plasmonic nucleic acid amplification tests demand high-throughput and multi-target detection of infectious diseases as well as short turnaround time and small size for point-of-care molecular diagnostics. Here, we report a multi-channel plasmonic real-time reverse-transcription polymerase chain reaction (mpRT-qPCR) assay for ultrafast and on-chip multi-target detection. The mpRT-qPCR system features two pairs of plasmonic thermocyclers for rapid nanostructure-driven amplification and microlens array fluorescence microscopes for in situ multi-color fluorescence quantification. Each channel shows a physical dimension of 32 mm, 75 mm, and 25 mm in width, length, and thickness. The ultrathin microscopes simultaneously capture four different fluorescence images from two PCR chambers of a single cartridge at a single shot exposure per PCR cycle of four different excitation light sources. The experimental results demonstrate a single assay result of high-throughput amplification and multi-target quantification for RNA-dependent RNA polymerase, nucleocapsid, and human ribonuclease P genes in SARS-CoV-2 RNA detection. The mpRT-PCR increases the number of tests four times over the single RT-PCR and exhibits a short detection time of 15 min for the four RT-PCR reactions. This point-of-care molecular diagnostic platform can reduce false negative results in clinical applications of virus detection and decentralize healthcare facilities with limited infrastructure.

Ultrafast Plasmonic Nucleic Acid Amplification and Real-Time Quantification for Decentralized Molecular Diagnostics.

Point-of-care real-time reverse-transcription polymerase chain reaction (RT-PCR) facilitates the widespread use of rapid, accurate, and cost-effective near-patient testing that is available to the public. Here, we report ultrafast plasmonic nucleic acid amplification and real-time quantification for decentralized molecular diagnostics. The plasmonic real-time RT-PCR system features an ultrafast plasmonic thermocycler (PTC), a disposable plastic-on-metal (PoM) cartridge, and an ultrathin microlens array fluorescence (MAF) microscope. The PTC provides ultrafast photothermal cycling under white-light-emitting diode illumination and precise temperature monitoring with an integrated resistance temperature detector. The PoM thin film cartridge allows rapid heat transfer as well as complete light blocking from the photothermal excitation source, resulting in real-time and highly efficient PCR quantification. Besides, the MAF microscope exhibits close-up and high-contrast fluorescence microscopic imaging. All of the systems were fully packaged in a palm size for point-of-care testing. The real-time RT-PCR system demonstrates the rapid diagnosis of coronavirus disease-19 RNA virus within 10 min and yields 95.6% of amplification efficiency, 96.6% of classification accuracy for preoperational test, and 91% of total percent agreement for clinical diagnostic test. The ultrafast and compact PCR system can decentralize point-of-care molecular diagnostic testing in primary care and developing countries.

Large-Area and Ultrathin MEMS Mirror Using Silicon Micro Rim.

A large-area and ultrathin MEMS (microelectromechanical system) mirror can provide efficient light-coupling, a large scanning area, and high energy efficiency for actuation. However, the ultrathin mirror is significantly vulnerable to diverse film deformation due to residual thin film stresses, so that high flatness of the mirror is hardly achieved. Here, we report a MEMS mirror of large-area and ultrathin membrane with high flatness by using the silicon rim microstructure (SRM). The ultrathin MEMS mirror with SRM (SRM-mirror) consists of aluminum (Al) deposited silicon nitride membrane, bimorph actuator, and the SRM. The SRM is simply fabricated underneath the silicon nitride membrane, and thus effectively inhibits the tensile stress relaxation of the membrane. As a result, the membrane has high flatness of 10.6 m-1 film curvature at minimum without any deformation. The electrothermal actuation of the SRM-mirror shows large tilting angles from 15° to -45° depending on the applied DC voltage of 0~4 VDC, preserving high flatness of the tilting membrane. This stable and statically actuated SRM-mirror spurs diverse micro-optic applications such as optical sensing, beam alignment, or optical switching.

Ultrathin arrayed camera for high-contrast near-infrared imaging.

We report an ultrathin arrayed camera (UAC) for high-contrast near infrared (NIR) imaging by using microlens arrays with a multilayered light absorber. The UAC consists of a multilayered composite light absorber, inverted microlenses, gap-alumina spacers and a planar CMOS image sensor. The multilayered light absorber was fabricated through lift-off and repeated photolithography processes. The experimental results demonstrate that the image contrast is increased by 4.48 times and the MTF 50 is increased by 2.03 times by eliminating optical noise between microlenses through the light absorber. The NIR imaging of UAC successfully allows distinguishing the security strip of authentic bill and the blood vessel of finger. The ultrathin camera offers a new route for diverse applications in biometric, surveillance, and biomedical imaging.

Multifocal microlens arrays using multilayer photolithography.

We report a new microfabrication method of multifocal microlens arrays (MF-MLAs) for extended depth-of-field (DoF) using multilayer photolithography and thermal reflow. Microlenses of different focal lengths were simultaneously fabricated on a single glass wafer by using repeated photolithography with multiple photomasks to define microposts of different thicknesses and concurrent thermal reflow of multi-stacked microposts. The diverse lens curvatures of MF-MLAs are precisely controlled by the thickness of the micropost. Hexagonally packaged MF-MLAs clearly show three different focal lengths of 249 µm, 310 µm, and 460 µm for 200 µm in lens diameter and result in multifocal images on a single image sensor. This method provides a new route for developing various three-dimensional (3D) imaging applications such as light-field cameras or 3D medical endoscopes.

Biologically inspired ultrathin arrayed camera for high-contrast and high-resolution imaging.

Compound eyes found in insects provide intriguing sources of biological inspiration for miniaturised imaging systems. Here, we report an ultrathin arrayed camera inspired by insect eye structures for high-contrast and super-resolution imaging. The ultrathin camera features micro-optical elements (MOEs), i.e., inverted microlenses, multilayered pinhole arrays, and gap spacers on an image sensor. The MOE was fabricated by using repeated photolithography and thermal reflow. The fully packaged camera shows a total track length of 740 µm and a field-of-view (FOV) of 73°. The experimental results demonstrate that the multilayered pinhole of the MOE allows high-contrast imaging by eliminating the optical crosstalk between microlenses. The integral image reconstructed from array images clearly increases the modulation transfer function (MTF) by ~1.57 times compared to that of a single channel image in the ultrathin camera. This ultrathin arrayed camera provides a novel and practical direction for diverse mobile, surveillance or medical applications.

Effects of Neuromuscular Electrical Stimulation for Masseter Muscle on Oral Dysfunction After Stroke.

OBJECTIVE: To determine positive effect of neuromuscular electrical stimulation (NMES) in conventional dysphagia therapy on masseter muscle oral dysfunction of patients after subacute stroke. METHODS: Among subacute stroke patients who were diagnosed as oropharyngeal dysphagia by videofluoroscopy swallowing study (VFSS), those with oral dysfunction were enrolled. They were randomly assigned to a study group or a control group. The study group received NMES on masseter muscle and suprahyoid muscle simultaneously, while the control group received NMES only on suprahyoid muscle. NMES therapy session as applied 30 minutes each time, two times per day for a total of 20 sessions. Both groups received conventional dysphagia therapy for 2 weeks. All enrolled patients were evaluated by VFSS after 2 weeks. Oropharyngeal swallowing function was evaluated by Penetration-Aspiration Scale, Functional Dysphagia Scale (FDS), and American Speech-Language-Hearing Association National Outcome Measurement System swallowing scale based on results of VFSS. RESULTS: Patients were randomly assigned to the study group (n=20) or the control group (n=20). There were no significant differences in baseline characteristics or initial values between the two groups. After 2 weeks of NMES, both groups showed improvement in scores of total FDS and pharyngeal phase FDS. Additionally, the study group showed improvement in oral phase FDS. Changes in all measurements were similar between the two groups. CONCLUSION: In this preliminary study, NMES for masseter muscle has a therapeutic effect on oral dysfunction of patients after subacute stroke.

Effects of mechanical inspiration and expiration exercise on velopharyngeal incompetence in subacute stroke patients.

OBJECTIVE: To investigate the therapeutic effects of mechanical inspiration and expiration exercise using mechanical cough assist on velopharyngeal incompetence in patients with subacute stroke. DESIGN: Pilot, randomized controlled study. SETTING: University-based rehabilitation centre. SUBJECTS: Thirty-six patients with subacute stroke diagnosed with velopharyngeal incompetence by videofluoroscopic swallowing study. METHODS: Subjects were randomly assigned to 2 groups. The study group received conventional dysphagia therapy and additional mechanical inspiration and expiration exercise. The control group received conventional dysphagia therapy only. Swallowing function was evaluated according to the American Speech-Language-Hearing association scale, functional dysphagia score, and the penetration aspiration scale, based on the videofluoroscopic swallowing study. Coughing function was measured using peak cough flow. RESULTS: Eighteen patients in each group completed the protocol and were analysed. After treatment, the study group showed significant improvement in functional dysphagia score with regard to nasal penetration degree. Comparing the treatment effect between the 2 groups, nasal penetration degree and peak cough flow showed greater improvement in the study group. CONCLUSION: Mechanical inspiration and expiration exercise had a therapeutic effect on velopharyngeal incompetence in subacute stroke patients with dysphagia. This therapy is easy to provide clinically and could be a useful therapeutic strategy for velo-pharyngeal incompetence with dysphagia in patients with stroke.

Xenos peckii vision inspires an ultrathin digital camera.

Increased demand for compact devices leads to rapid development of miniaturized digital cameras. However, conventional camera modules contain multiple lenses along the optical axis to compensate for optical aberrations that introduce technical challenges in reducing the total thickness of the camera module. Here, we report an ultrathin digital camera inspired by the vision principle of Xenos peckii, an endoparasite of paper wasps. The male Xenos peckii has an unusual visual system that exhibits distinct benefits for high resolution and high sensitivity, unlike the compound eyes found in most insects and some crustaceans. The biologically inspired camera features a sandwiched configuration of concave microprisms, microlenses, and pinhole arrays on a flat image sensor. The camera shows a field-of-view (FOV) of 68 degrees with a diameter of 3.4 mm and a total track length of 1.4 mm. The biologically inspired camera offers a new opportunity for developing ultrathin cameras in medical, industrial, and military fields.

Angle-selective optical filter for highly sensitive reflection photoplethysmogram.

We report an angle-selective optical filter (ASOF) for highly sensitive reflection photoplethysmography (PPG) sensors. The ASOF features slanted aluminum (Al) micromirror arrays embedded in transparent polymer resin, which effectively block scattered light under human tissue. The device microfabrication was done by using geometry-guided resist reflow of polymer micropatterns, polydimethylsiloxane replica molding, and oblique angle deposition of thin Al film. The angular transmittance through the ASOF is precisely controlled by the angle of micromirrors. For the mirror angle of 30 degrees, the ASOF accepts an incident light between - 90 to + 50 degrees and the maximum transmittance at - 55 degrees. The ASOF exhibits the substantial reduction of both the in-band noise of PPG signals over a factor of two and the low-frequency noise by three times. Consequently, this filter allows distinguishing the diastolic peak that allows miscellaneous parameters with diverse vascular information. This optical filter provides a new opportunity for highly sensitive PPG monitoring or miscellaneous optical tomography.

Electrothermal MEMS parallel plate rotation for single-imager stereoscopic endoscopes.

This work reports electrothermal MEMS parallel plate-rotation (PPR) for a single-imager based stereoscopic endoscope. A thin optical plate was directly connected to an electrothermal MEMS microactuator with bimorph structures of thin silicon and aluminum layers. The fabricated MEMS PPR device precisely rotates an transparent optical plate up to 37° prior to an endoscopic camera and creates the binocular disparities, comparable to those from binocular cameras with a baseline distance over 100 µm. The anaglyph 3D images and disparity maps were successfully achieved by extracting the local binocular disparities from two optical images captured at the relative positions. The physical volume of MEMS PPR is well fit in 3.4 mm x 3.3 mm x 1 mm. This method provides a new direction for compact stereoscopic 3D endoscopic imaging systems.

Compact stereo endoscopic camera using microprism arrays.

This work reports a microprism array (MPA) based compact stereo endoscopic camera with a single image sensor. The MPAs were monolithically fabricated by using two-step photolithography and geometry-guided resist reflow to form an appropriate prism angle for stereo image pair formation. The fabricated MPAs were transferred onto a glass substrate with a UV curable resin replica by using polydimethylsiloxane (PDMS) replica molding and then successfully integrated in front of a single camera module. The stereo endoscopic camera with MPA splits an image into two stereo images and successfully demonstrates the binocular disparities between the stereo image pairs for objects with different distances. This stereo endoscopic camera can serve as a compact and 3D imaging platform for medical, industrial, or military uses.