A Mechanically Flexible, Implantable Neural Interface for Computational Imaging and Optogenetic Stimulation Over 5.4×5.4mm2 FoV.

Emerging optical functional imaging and optogenetics are among the most promising approaches in neuroscience to study neuronal circuits. Combining both methods into a single implantable device enables all-optical neural interrogation with immediate applications in freely-behaving animal studies. In this paper, we demonstrate such a device capable of optical neural recording and stimulation over large cortical areas. This implantable surface device exploits lens-less computational imaging and a novel packaging scheme to achieve an ultra-thin (250µm-thick), mechanically flexible form factor. The core of this device is a custom-designed CMOS integrated circuit containing a 160×160 array of time-gated single-photon avalanche photodiodes (SPAD) for low-light intensity imaging and an interspersed array of dual-color (blue and green) flip-chip bonded micro-LED (µLED) as light sources. We achieved 60µm lateral imaging resolution and 0.2mm3 volumetric precision for optogenetics over a 5.4×5.4mm2 field of view (FoV). The device achieves a 125-fps frame-rate and consumes 40 mW of total power.

An Integrated 2D Ultrasound Phased Array Transmitter in CMOS With Pixel Pitch-Matched Beamforming.

Emerging non-imaging ultrasound applications, such as ultrasonic wireless power delivery to implantable devices and ultrasound neuromodulation, require wearable form factors, millisecond-range pulse durations and focal spot diameters approaching 100 µm with electronic control of its three-dimensional location. None of these are compatible with typical handheld linear array ultrasound imaging probes. In this work, we present a 4 mm × 5 mm 2D ultrasound phased array transmitter with integrated piezoelectric ultrasound transducers on complementary metal-oxide-semiconductor (CMOS) integrated circuits, featuring pixel-level pitch-matched transmit beamforming circuits which support arbitrary pulse duration. Our direct integration method enabled up to 10 MHz ultrasound arrays in a patch form-factor, leading to focal spot diameter of ∼200 µm, while pixel pitch-matched beamforming allowed for precise three-dimensional positioning of the ultrasound focal spot. Our device has the potential to provide a high-spatial resolution and wearable interface to both powering of highly-miniaturized implantable devices and ultrasound neuromodulation.

Biosensors for On-Farm Diagnosis of Mastitis.

Bovine mastitis is an inflammation of the mammary gland caused by a multitude of pathogens with devastating consequences for the dairy industry. Global annual losses are estimated to be around €30 bn and are caused by significant milk losses, poor milk quality, culling of chronically infected animals, and occasional deaths. Moreover, mastitis management routinely implies the administration of antibiotics to treat and prevent the disease which poses serious risks regarding the emergence of antibiotic resistance. Conventional diagnostic methods based on somatic cell counts (SCC) and plate-culture techniques are accurate in identifying the disease, the respective infectious agents and antibiotic resistant phenotypes. However, pressure exists to develop less lengthy approaches, capable of providing on-site information concerning the infection, and in this way, guide, and hasten the most adequate treatment. Biosensors are analytical tools that convert the presence of biological compounds into an electric signal. Benefitting from high signal-to-noise ratios and fast response times, when properly tuned, they can detect the presence of specific cells and cell markers with high sensitivity. In combination with microfluidics, they provide the means for development of automated and portable diagnostic devices. Still, while biosensors are growing at a fast pace in human diagnostics, applications for the veterinary market, and specifically, for the diagnosis of mastitis remain limited. This review highlights current approaches for mastitis diagnosis and describes the latest outcomes in biosensors and lab-on-chip devices with the potential to become real alternatives to standard practices. Focus is given to those technologies that, in a near future, will enable for an on-farm diagnosis of mastitis.

Go with the flow: advances and trends in magnetic flow cytometry.

The growing need for biological information at the single cell level has driven the development of improved cytometry technologies. Flow cytometry is a particularly powerful method that has evolved over the past few decades. Flow cytometers have become essential instruments in biomedical research and routine clinical tests for disease diagnosis, prognosis, and treatment monitoring. However, the increasing number of cellular parameters unveiled by genomic, proteomic, and metabolomic data platforms demands an augmented multiplexability. Also, the need for identification and quantification of relevant biomarkers at low levels requires outstanding analytical sensitivity and reliability. In addition, growing awareness of the advantages associated with miniaturization of analytical devices is pushing forward the progress in integrated and compact, microfluidic-based devices at the point-of-care. In this context, novel types of flow cytometers are emerging during the search to tackle these challenges. Notwithstanding the relevance of other promising alternatives to standard optical flow cytometry (e.g., mass cytometry, various optical and electrical microcytometers), this report focuses on a recent microcytometric technology based on magnetic sensors and magnetic particles integrated into microfluidic structures for dynamic bioanalysis of fluid samples-magnetic flow cytometry. Its concept, main developments, targeted applications, as well as the challenges and trends behind this technology are presented and discussed. Graphical abstract ᅟ "Kindly advise whether there is online abstract figure for this paper. If so, kindly resupply.The graphical abstract is correctly supplied.

Lab-on-Chip Devices: Gaining Ground Losing Size.

Portable analytical devices are notably gaining relevance in the panorama of urgent testing. Such devices have the potential to play an important role as easy-to-handle tools in critical situations. Epidemic infectious disease agents (e.g., Ebola virus, Coronavirus, Zika virus) could be controlled more easily by testing travelers on-site at the country borders to prevent outbreaks from spreading. The increasing incidence of hospital-acquired infections caused by antibiotic resistant pathogens could be minimized by point-of-care microbial analysis as well as rapid screening tests of bacteria resistance. The threat of bioterrorism using novel unknown bioweapons has never been so high, thus, in-the-field early identification of the biological agent is crucial for triggering a coordinated response. Food allergies are a growing public health concern-allergic reactions can result in anaphylactic shock, which can prove fatal in minutes-thus, the ability to test foods for common allergens, rapidly and locally, before ingestion, would improve food safety for those with allergies. Lab-on-chip devices are becoming widely available for diverse applications and are becoming increasingly affordable. However, to shrink in price and size simultaneously, some trade-offs must be made. In this Perspective, we present considerations about product specifications, design concepts, and application scenarios.

A CMOS Front-End With Integrated Magnetoresistive Sensors for Biomolecular Recognition Detection Applications.

The development of giant magnetoresistive (GMR) sensors has demonstrated significant advantages in nanomedicine, particularly for ultrasensitive point-of-care diagnostics. To this end, the detection system is required to be compact, portable, and low power consuming at the same time that a maximum signal to noise ratio is maintained. This paper reports a CMOS front-end with integrated magnetoresistive sensors for biomolecular recognition detection applications. Based on the characterization of the GMR sensor's signal and noise, CMOS building blocks (i.e., current source, multiplexers, and preamplifier) were designed targeting a negligible noise when compared with the GMR sensor's noise and a low power consumption. The CMOS front-end was fabricated using AMS [Formula: see text] technology and the magnetoresistive sensors were post-fabricated on top of the CMOS chip with high yield ( [Formula: see text]). Due to its low circuit noise (16 [Formula: see text]) and overall equivalent magnetic noise ([Formula: see text]), the full system was able to detect 250 nm magnetic nanoparticles with a circuit imposed signal-to-noise ratio degradation of only -1.4 dB. Furthermore, the low power consumption (6.5 mW) and small dimensions ([Formula: see text] ) of the presented solution guarantees the portability of the detection system allowing its usage at the point-of-care.

Lab-on-chip cytometry based on magnetoresistive sensors for bacteria detection in milk.

Flow cytometers have been optimized for use in portable platforms, where cell separation, identification and counting can be achieved in a compact and modular format. This feature can be combined with magnetic detection, where magnetoresistive sensors can be integrated within microfluidic channels to detect magnetically labelled cells. This work describes a platform for in-flow detection of magnetically labelled cells with a magneto-resistive based cell cytometer. In particular, we present an example for the validation of the platform as a magnetic counter that identifies and quantifies Streptococcus agalactiae in milk.

A portable and autonomous magnetic detection platform for biosensing.

This paper presents a prototype of a platform for biomolecular recognition detection. The system is based on a magnetoresistive biochip that performs biorecognition assays by detecting magnetically tagged targets. All the electronic circuitry for addressing, driving and reading out signals from spin-valve or magnetic tunnel junctions sensors is implemented using off-the-shelf components. Taking advantage of digital signal processing techniques, the acquired signals are processed in real time and transmitted to a digital analyzer that enables the user to control and follow the experiment through a graphical user interface. The developed platform is portable and capable of operating autonomously for nearly eight hours. Experimental results show that the noise level of the described platform is one order of magnitude lower than the one presented by the previously used measurement set-up. Experimental results also show that this device is able to detect magnetic nanoparticles with a diameter of 250 nm at a concentration of about 40 fM. Finally, the biomolecular recognition detection capabilities of the platform are demonstrated by performing a hybridization assay using complementary and non-complementary probes and a magnetically tagged 20mer single stranded DNA target.