Three-dimensional electronic microfliers inspired by wind-dispersed seeds.

Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds6-we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.

Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity.

For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.

High-speed volumetric imaging of neuronal activity in freely moving rodents.

Thus far, optical recording of neuronal activity in freely behaving animals has been limited to a thin axial range. We present a head-mounted miniaturized light-field microscope (MiniLFM) capable of capturing neuronal network activity within a volume of 700 × 600 × 360 µm3 at 16 Hz in the hippocampus of freely moving mice. We demonstrate that neurons separated by as little as ~15 µm and at depths up to 360 µm can be discriminated.

µ-NMR at the point of care testing.

NMR shows strong analytical capability for obtaining molecular information on materials and is used in a variety of fields. Micro-NMR (µNMR) is mainly based on low-field NMR (LF-NMR), which makes NMR detection portable and inexpensive. Point-of-care testing (POCT) has gradually become an area of major concern, and scientists have made much progress in applying µNMR systems for POCT. To the best of our knowledge, this is the first review of the latest development in miniaturization of µNMR systems. Then, we discuss cutting-edge µNMR-based applications in POCT and the outlook for future developments.

Miniature all-optical flexible forward-viewing photoacoustic endoscopy probe for surgical guidance.

A miniature flexible photoacoustic endoscopy probe that provides high-resolution 3D images of vascular structures in the forward-viewing configuration is described. A planar Fabry-Perot ultrasound sensor with a -3dB bandwidth of 53 MHz located at the tip of the probe is interrogated via a flexible fiber bundle and a miniature optical relay system to realize an all-optical probe measuring 7.4 mm in outer diameter at the tip. This approach to photoacoustic endoscopy offers advantages over previous piezoelectric based distal-end scanning probes. These include a forward-viewing configuration in widefield photoacoustic tomography mode, finer spatial sampling (87 µm spatial sampling interval), and wider detection bandwidth (53 MHz) than has been achievable with conventional ultrasound detection technology and an all-optical passive imaging head for safe endoscopic use.

Miniaturized precalibration-based Lissajous scanning fiber probe for high speed endoscopic optical coherence tomography.

We present a miniaturized precalibration-based forward-viewing Lissajous scanning fiber probe for high speed endoscopic optical coherence tomography (OCT). The probe is based on an asymmetric fiber cantilever driven by the piezoelectric bender to realize two-dimensional (2D) Lissajous scanning. The stability and repeatability of the Lissajous scanning trajectory of the probe is tested by a position sensitive detector (PSD)-based position calibration setup. The two orthogonal resonant frequencies of the cantilever are measured to be 167.2 and 121 Hz. A 25 µm focal spot is formed at the working distance of 5 mm by the graded-index (GRIN) lens, and the field of view of the imaging probe is around ${1.5}\;{\rm mm} \times {1.5}\;{\rm mm}$1.5mm×1.5mm. The probe is fully packaged in a hypodermic tube for endoscopic imaging. The total rigid length and outer diameter are 35 mm and 3.5 mm, respectively. The probe is incorporated in a 50 KHz swept source OCT system with the axial resolution of 14 µm, and its imaging performance is validated by the 2D en face and 3D volumetric OCT imaging of the phantom and the biological tissue.

The detection of cannabinoids in veterinary feeds by microNIR/chemometrics: a new analytical platform.

In this work, the capabilities of a novel miniaturized and portable microNIR spectrometer were investigated in order to propose a practical and intelligible test allowing the rapid and easy screening of cannabinoids in veterinary feeds. In order to develop a predictive model that could identify and simultaneously quantify the residual amounts of cannabinoids, specimens from popular veterinary feeds were considered and spiked with increasing amounts of cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC), and cannabigerol (CBG). Partial least squares discriminant analysis (PLS-DA) and partial least squares regression (PLSr) were applied for the simultaneous detection and quantification of cannabinoids. The results demonstrated that the microNIR/chemometric platform could statistically identify the presence of CBD, THC and CBG in the simulated samples containing cannabinoids from 0.001 to 0.01%w/w, with the accuracy and sensitivity of the official reference methods actually proposed. The method was checked against false positive and true positive responses, and the results proved to be those required for confirmatory analyses, permitting to provide a fast and accurate method for monitoring cannabinoids in veterinary feeds.

Miniaturized optical fiber tweezers for cell separation by optical force.

In advanced biomedicine and microfluidics, there is a strong desire to sort and manipulate various cells and bacteria based on miniaturized microfluidic chips. Here, by integrating fiber tweezers into a T-type microfluidic channel, we report an optofluidic chip to selectively trap Escherichia coli in human blood solution based on different sizes and shapes. Furthermore, we simulate the trapping and pushing regions of other cells and bacteria, including rod-shaped bacteria, sphere-shaped bacteria, and cancer cells based on finite-difference analysis. With the advantages of controllability, low optical power, and compact construction, the strategy may be possibly applied in the fields of optical separation, cell transportation, and water quality analysis.

Going big versus going small: Lithic miniaturization in hominin lithic technology.

Lithic miniaturization was one of our Pleistocene ancestors' more pervasive stone tool production strategies and it marks a key difference between human and non-human tool use. Frequently equated with "microlith" production, lithic miniaturization is a more complex, variable, and evolutionarily consequential phenomenon involving small backed tools, bladelets, small retouched tools, flakes, and small cores. In this review, we evaluate lithic miniaturization's various technological and functional elements. We examine archeological assumptions about why prehistoric stoneworkers engaged in processes of lithic miniaturization by making small stone tools, small elongated tools, and small retouched and backed tools. We point to functional differences that motivate different aspects of lithic miniaturization and several instances where archeological systematics have possibly led archeologists to false negative findings about lithic miniaturization. Finally, we suggest productive avenues by which archeologists can move closer to understanding the complex evolutionary forces driving variability in lithic miniaturization.

A concentric tube-based 4-DOF puncturing needle with a novel miniaturized actuation system for vitrectomy.

BACKGROUND: Vitreoretinal surgeries require precise, dexterous, and steady instruments for operation in delicate parts of the eye. Robotics has presented solutions for many vitreoretinal surgical problems, but, in a few operations, the available tools are still not dexterous enough to carry out procedures with minimum trauma to patients. Vitrectomy is one of those procedures and requires some dexterous instruments to replace straight ones for better navigation to affected sides inside the eyeball. METHOD: In this paper, we propose a new vein puncturing solution with a 4-DOF motion to increase the workspace inside the eye. A two-member concentric tube-based 25G needle is proposed whose shape is optimized. To operate the concentric tube needle, a novel and miniaturized actuation system is proposed that uses hollow shaft motors for the first time. The presented prototype of actuation system has a stroke of 100 mm in a small size of 148 × 25 × 65 mm (L × W × H), suitable for approaching distant positions inside the eyeball. RESULTS: Experimental results validate that the targeting accuracy of the needle is less than one millimeter and the needle tip can apply a force of 23.51 mN which is enough to perform puncturing. Furthermore, the proposed needle covers maximum workspace of around 128.5° inside the eyeball. For the actuation system, experiments show that it can produce repeatable motions with accuracy in submillimeter. CONCLUSION: The proposed needle system can navigate to the sites which are difficult to approach by currently available straight tools requiring reinsertions. Along with the miniaturized actuation system, this work is expected to improve the outcome of vitrectomy with safe and accurate navigation.

Handheld Microflow Cytometer Based on a Motorized Smart Pipette, a Microfluidic Cell Concentrator, and a Miniaturized Fluorescence Microscope.

Miniaturizing flow cytometry requires a comprehensive approach to redesigning the conventional fluidic and optical systems to have a small footprint and simple usage and to enable rapid cell analysis. Microfluidic methods have addressed some challenges in limiting the realization of microflow cytometry, but most microfluidics-based flow cytometry techniques still rely on bulky equipment (e.g., high-precision syringe pumps and bench-top microscopes). Here, we describe a comprehensive approach that achieves high-throughput white blood cell (WBC) counting in a portable and handheld manner, thereby allowing the complete miniaturization of flow cytometry. Our approach integrates three major components: a motorized smart pipette for accurate volume metering and controllable liquid pumping, a microfluidic cell concentrator for target cell enrichment, and a miniaturized fluorescence microscope for portable flow cytometric analysis. We first validated the capability of each component by precisely metering various fluid samples and controlling flow rates in a range from 219.5 to 840.5 µL/min, achieving high sample-volume reduction via on-chip WBC enrichment, and successfully counting single WBCs flowing through a region of interrogation. We synergistically combined the three major components to create a handheld, integrated microflow cytometer and operated it with a simple protocol of drawing up a blood sample via pipetting and injecting the sample into the microfluidic concentrator by powering the motorized smart pipette. We then demonstrated the utility of the microflow cytometer as a quality control means for leukoreduced blood products, quantitatively analyzing residual WBCs (rWBCs) in blood samples present at concentrations as low as 0.1 rWBCs/µL. These portable, controllable, high-throughput, and quantitative microflow cytometric technologies provide promising ways of miniaturizing flow cytometry.

Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice.

To enable sophisticated optogenetic manipulation of neural circuits throughout the nervous system with limited disruption of animal behavior, light-delivery systems beyond fiber optic tethering and large, head-mounted wireless receivers are desirable. We report the development of an easy-to-construct, implantable wireless optogenetic device. Our smallest version (20 mg, 10 mm(3)) is two orders of magnitude smaller than previously reported wireless optogenetic systems, allowing the entire device to be implanted subcutaneously. With a radio-frequency (RF) power source and controller, this implant produces sufficient light power for optogenetic stimulation with minimal tissue heating (<1 °C). We show how three adaptations of the implant allow for untethered optogenetic control throughout the nervous system (brain, spinal cord and peripheral nerve endings) of behaving mice. This technology opens the door for optogenetic experiments in which animals are able to behave naturally with optogenetic manipulation of both central and peripheral targets.

Characterization of a novel miniaturized burst-mode infrared laser system for IR-MALDESI mass spectrometry imaging.

Laser systems are widely used in mass spectrometry as sample probes and ionization sources. Mid-infrared lasers are particularly suitable for analysis of high water content samples such as animal and plant tissues, using water as a resonantly excited sacrificial matrix. Commercially available mid-IR lasers have historically been bulky and expensive due to cooling requirements. This work presents a novel air-cooled miniature mid-IR laser with adjustable burst-mode output and details an evaluation of its performance for mass spectrometry imaging. The miniature laser was found capable of generating sufficient energy for complete ablation of animal tissue in the context of an IR-MALDESI experiment with exogenously added ice matrix, yielding several hundred confident metabolite identifications. Graphical abstract The use of a novel miniature 2.94 µm burst-mode laser in IR-MALDESI allows for rapid and sensitive mass spectrometry imaging of a whole mouse.

Monitoring enzymatic degradation of emerging contaminants using a chip-based robotic nano-ESI-MS tool.

Up to now, knowledge of enzymes capable of degrading various contaminants of emerging concern (CEC) is limited, which is especially due to the lack of rapid screening methods. Thus, a miniaturized high-throughput setup using a chip-based robotic nanoelectrospray ionization system coupled to mass spectrometry has been developed to rapidly screen enzymatic reactions with environmentally relevant CECs. Three laccases, two tyrosinases, and two peroxidases were studied for their ability to transform ten pharmaceuticals and benzotriazole. Acetaminophen was most susceptible to enzymatic conversion by horseradish peroxidase (HRP), laccase from Trametes versicolor (LccTV), and a tyrosinase from Agaricus bisporus (TyrAB). Diclofenac and mefenamic acid were converted by HRP and LccTV, whereas sotalol was solely amenable to HRP conversion. Benzotriazole, carbamazepine, gabapentin, metoprolol, primidone, sulfamethoxazole, and venlafaxine remained persistent in this study. The results obtained here emphasize that enzymes are highly selective catalysts and more effort is required in the use of fast monitoring technologies to find suitable enzyme systems. Despite the methodological limitations discussed in detail, the automated tool provides a routine on-line screening of various enzymatic reactions to identify potential enzymes that degrade CECs. Graphical abstract A chip-based robotic nano-ESI-MS tool to rapidly monitor enzymatic degradation of environmentally relevant emerging contaminants.

Comparison of synthetic aperture architectures for miniaturised ultrasound imaging front-ends.

BACKGROUND: Point of care ultrasonography has been the focus of extensive research over the past few decades. Miniaturised, wireless systems have been envisaged for new application areas, such as capsule endoscopy, implantable ultrasound and wearable ultrasound. The hardware constraints of such small-scale systems are severe, and tradeoffs between power consumption, size, data bandwidth and cost must be carefully balanced. METHODS: In this work, two receiver architectures are proposed and compared to address these challenges. Both architectures uniquely combine low-rate sampling with synthetic aperture beamforming to reduce the data bandwidth and system complexity. The first architecture involves the use of quadrature sampling to minimise the signal bandwidth and computational load. Synthetic aperture beamforming (SAB) is carried out using a single-channel, pipelined protocol suitable for implementation on an FPGA/ASIC. The second architecture employs compressive sensing within the finite rate of innovation framework to further reduce the bandwidth. Low-rate signals are transmitted to a computational back-end (computer), which sequentially reconstructs each signal and carries out beamforming. RESULTS: Both architectures were tested using a custom hardware front-end and synthetic aperture database to yield B-mode images. The normalised root-mean-squared-error between the quadrature SAB image and the RF reference image was [Formula: see text] while the compressive SAB error was [Formula: see text] for the same degree of spatial compounding. The sampling rate is reduced by a factor of 2 (quadrature SAB) and 4.7 (compressive SAB), compared to the RF sampling rate. The quadrature method is implemented on FPGA, with a total power consumption of [Formula: see text] mW, which is comparable to state-of-the-art hardware topologies, but with significantly reduced circuit area. CONCLUSIONS: Through a novel combination of SAB and low-rate sampling techniques, the proposed architectures achieve a significant reduction in data transmission rate, system complexity and digital/analogue circuit area. This allows for aggressive miniaturisation of the imaging front-end in portable imaging applications.

Tailored Holder for Continuous Echocardiographic Monitoring.

Hemodynamic monitoring is essential for prompt and effective interventions in intensive care unit patients. We developed a custom-made transthoracic echocardiography transducer holder consisting of transducer holder and skin patch attachment. This holder allowed continuous transthoracic echocardiography monitoring in 5 adult patients with circulatory failure due to shock, and 6 pediatric patients after successful percutaneous closure of a ventricular septal defect. One case of an unexpected hemopericardium was promptly diagnosed and pericardiocentesis was performed, and 1 patient required extracorporeal membrane oxygenation support.

Miniaturized Biomedical Sensors for Enumeration of Extracellular Vesicles.

In this research, we have realized a rapid extracellular vesicle (EV) quantification methodology using a high field modulated AlGaN/GaN high electron mobility (HEMT) biosensor. The unique sensing structure facilitated the detection of the sub-cellular components in physiological salt environment without requiring extensive sample pre-treatments. The high field operation of GaN HEMT biosensor provides high sensitivity and wide dynamic range of detection of EVs (107⁻1010 EVs/mL). An antibody specific to the known surface marker on the EV was used to capture them for quantification using an HEMT biosensor. Fluorescence microscopy images confirm the successful capture of EVs from the test solution. The present method can detect EVs in high ionic strength solution, with a short sample incubation period of 5 min, and does not require labels or additional reagents or wash/block steps. This methodology has the potential to be used in clinical applications for rapid EV quantification from blood or serum for the development of diagnostic and prognostic tools.

A miniaturized sensor for detection of formaldehyde fumes.

A miniaturized chemical sensor is here described for the analysis of environmental pollutants (VOC: volatile organic chemicals). It is used for remote detection of formaldehyde (FA) fumes in the atmosphere, and is based on the redox reaction between FA and silver nitrate. The sensor is worn as a bracelet and the data acquired are transferred via a Bluetooth channel to a smartphone. A dedicated software transforms the signal from a grey to a color scale. The signal response has been assessed over low (20 to 120 ppb) as well as higher (1-15 ppm range) levels. The sensor has been applied to monitor potential FA fumes of some artwork in the Summer Palace in Beijing and the modifications induced by FA treatment on a precious Stradivarius violin. The performance of this novel sensor is compared with a commercial apparatus widely adopted, namely the Honeywell MultiRAE Lite wireless portable multi-gas monitor (pumped model).

The new generation super-mini percutaneous nephrolithotomy (SMP) system: a step-by-step guide.

OBJECTIVE: To present our novel miniaturised endoscopic system and describe a step-by-step guide for successful implementation of the super-mini percutaneous nephrolithotomy (SMP). PATIENTS AND METHODS: The new-generation SMP endoscopic system consists of (i) a 40 000-pixel super-mini nephroscope with an 8.0-F outer diameter and 7.5-F inner diameter dismountable sheath, and (ii) a newly designed irrigation-suction sheath available in either 12 F or 14 F. The irrigation-suction sheath is a two-layered metal structure. The key feature of the irrigation-suction sheath is to allow irrigation and suction respectively (the inflow through the space between the two layers of the sheath, the outflow through the central lumen of the sheath). This property improves irrigation and stone clearance despite reduced instrument dimension. In all, 59 patients with renal stones underwent new-generation SMP between April 2016 and December 2016. The percutaneous tract dilatation was carried out to 14 F. Lithotripsy was performed using either holmium laser or a pneumatic lithotripter. Stone fragments were sucked out by vacuum suctioning through the sheath. A nephrostomy tube or JJ stent was placed only if clinically indicated. Low-dose computed tomography was performed to assess the stone-free status on the morning after the procedure. RESULTS: The mean stone burden was 2.4 cm. Of the 59 patients, nine had diabetes and five had hypertension. SMP was completed successfully in all patients with a mean operation duration of 32.9 min and a mean haemoglobin decrease of 13 g/L. The stone-free rate was 91.5%. Complications occurred in 5.1% of the patients, all of them were Clavien-Dindo Grade I (minor fever managed by antipyretic therapy), and no transfusions were needed. CONCLUSION: The new-generation SMP system is safe, feasible, and effective for managing renal calculi of <3 cm, with the advantages of a small percutaneous tract, less blood loss, high efficacy in stone clearance, improved visual field, short operation duration, and ease of operating.