Super-Resolution and Wide-Field-of-View Imaging Based on Large-Angle Deflection with Risley Prisms.

A novel single camera combined with Risley prisms is proposed to achieve a super-resolution (SR) imaging and field-of-view extension (FOV) imaging method. We develop a mathematical model to consider the imaging aberrations caused by large-angle beam deflection and propose an SR reconstruction scheme that uses a beam backtracking method for image correction combined with a sub-pixel shift alignment technique. For the FOV extension, we provide a new scheme for the scanning position path of the Risley prisms and the number of image acquisitions, which improves the acquisition efficiency and reduces the complexity of image stitching. Simulation results show that the method can increase the image resolution to the diffraction limit of the optical system for imaging systems where the resolution is limited by the pixel size. Experimental results and analytical verification yield that the resolution of the image can be improved by a factor of 2.5, and the FOV extended by a factor of 3 at a reconstruction factor of 5. The FOV extension is in general agreement with the simulation results. Risley prisms can provide a more general, low-cost, and efficient method for SR reconstruction, FOV expansion, central concave imaging, and various scanning imaging.

Programmable liquid crystal display based noise reduced dynamic synthetic coded aperture imaging camera (NoRDS-CAIC).

Besides traditional lens-based imaging techniques, coded aperture imaging (CAI) can also provide target images but without using any optical lenses, therefore it is another solution in imaging applications. Most CAI methods reconstruct target image only from a single-shot coded image using a fixed coding mask; however, the collected partial information inevitably deteriorates the reconstruction quality. Though multi-exposure CAI methods are designed, these existed algorithms can hardly improve reconstruction signal-to-noise ratio (SNR) and spatial resolution simultaneously; additionally, dynamic coding mask display still requires expensive devices and complicated systems. In order to reconstruct target image with both enhanced spatial resolution and SNR but using cost-effective devices and a simple system, we design a noise reduced dynamic synthetic coded aperture imaging camera (NoRDS-CAIC) in this paper. The NoRDS-CAIC only consists of a programmable liquid crystal display (LCD) and an image recorder, and both of them are integrated with a three-dimensional printed shell with the compact size of 19 cm × 15 cm × 16 cm and controlled by our designed software to automatically realize coding mask display, coded image recording and target image reconstruction. When using the NoRDS-CAIC, the optimized coding mask is first sent to the programmable LCD and displayed, then the corresponding coded image is automatically captured using the image recorder. Next, cycle the above procedures to capture enough coded images with previously known coding masks and measured point spread functions (PSFs), and the target image can be finally reconstructed using our designed NoRDS-CAIC decoding algorithm, which is shown with better noise suppression capability and higher reconstruction resolution compared to other classical CAI algorithms. According to the experimental verifications, the NoRDS-CAIC can reach the high resolution of 99.2 µm and the high SNR of 19.43 dB, proving that the designed NoRDS-CAIC can be potentially used for lensless imaging in practical applications.

A portable Raspberry Pi-based spectrometer for on-site spectral testing.

We designed a portable Raspberry Pi-based spectrometer, which mainly consists of a white LED acting as the wide-spectrum source, a reflection grating for light dispersion, and a CMOS imaging chip aiming at spectral recording. All the optical elements and Raspberry Pi were integrated using 3-D printing structures with a size of 118 mm × 92 mm × 84 mm, and home-built software was also designed for spectral recording, calibration, analysis, and display implemented with a touch LCD. Additionally, the portable Raspberry Pi-based spectrometer was equipped with an internal battery, thus supporting on-site applications. Tested by a series of verifications and applications, the portable Raspberry Pi-based spectrometer could reach a spectral resolution of 0.065 nm per pixel within the visible band and provide spectral detection with high accuracy. Therefore, it can be used for on-site spectral testing in various fields.

Portable high-throughput multimodal immunoassay platform for rapid on-site COVID-19 diagnostics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a causal agent of Coronavirus Disease 2019 (COVID-19) has led to the global pandemic. Though the real-time reverse transcription polymerase chain reaction (RT-PCR) acting as a gold-standard method has been widely used for COVID-19 diagnostics, it can hardly support rapid on-site applications or monitor the stage of disease development as well as to identify the infection and immune status of rehabilitation patients. To suit rapid on-site COVID-19 diagnostics under various application scenarios with an all-in-one device and simple detection reagents, we propose a high-throughput multimodal immunoassay platform with fluorescent, colorimetric, and chemiluminescent immunoassays on the same portable device and a multimodal reporter probe using quantum dot (QD) microspheres modified with horseradish peroxidase (HRP) coupled with goat anti-human IgG. The recombinant nucleocapsid protein fixed on a 96-well plate works as the capture probe. In the condition with the target under detection, both reporter and capture probes can be bound by such target. When illuminated by excitation light, fluorescence signals from QD microspheres can be collected for target quantification often at a fast speed. Additionally, when pursuing simple detection without using any sensing devices, HRP-catalyzed TMB colorimetric immunoassay is employed; and when pursuing highly sensitive detection, HRP-catalyzed luminol chemiluminescent immunoassay is established. Verified by the anti-SARS-CoV-2 N humanized antibody, the sensitivities of colorimetric, fluorescent, and chemiluminescent immunoassays are respectively 20, 80, and 640 times more sensitive than that of the lateral flow colloidal gold immunoassay strip. Additionally, such a platform can simultaneously detect multiple samples at the same time thus supporting high-throughput sensing; and all these detecting operations can be implemented on-site within 50 min relying on field-operable processing and field-portable devices. Such a high-throughput multimodal immunoassay platform can provide a new all-in-one solution for rapid on-site diagnostics of COVID-19 for different detecting purposes.

Quantum dot microsphere-based immunochromatography test strip enabled sensitive and quantitative on-site detections for multiple mycotoxins in grains.

In this work, we design a sensitive and quantitative on-site detecting solution for Aflatoxin B1 (AFB1), Ochratoxin A (OTA) and Zearalenone (ZEN) as often found in moldy grains and harmful to human health. Using quantum dot microsphere-based immunochromatography test strip, the proposed method can sensitively detect AFB1, OTA and ZEN in low detection limits of 0.01 ng/mL, 0.2 ng/mL and 0.032 ng/mL, and quantitatively measure their concentrations from 0.01 ng/mL to 1 ng/mL, from 0.2 ng/mL to 200 ng/mL and from 0.032 ng/mL to 32 ng/mL in high accuracy and good selectivity. More importantly, these multiple mycotoxin detections only relying on simple manual operations and portable handheld test strip reader can be finished on site within 45 min. Therefore, the proposed method is a promising solution supporting sensitive and quantitative on-site detections for multiple mycotoxins.

Quantitative ciprofloxacin on-site rapid detections using quantum dot microsphere based immunochromatographic test strips.

The ciprofloxacin (CIP) abuse has caused many problems threatening to human health. Here, we design the quantum dot microsphere (QDM) based immunochromatographic quantitative CIP test strip: when the sample under detection contains CIP, the QDM-monoclonal antibody (mAb) probes bound with the CIP and cannot be captured by CIP-bovine serum albumin (BSA) conjugation dispersed on the T lines, reducing the fluorescence intensities. These test strips can provide a low detection limit of 0.05 ng/mL and a wide linear detection range from 0.1 ng/mL to 100 ng/mL in high sensitivity and accuracy as well as good selectivity, reproducibility and stability. Moreover, a smartphone based test strip reader with the size of 85 mm × 48 mm × 44 mm is also fabricated using 3-D printing to automatically and quantitatively detect CIP. The whole process of CIP detection can be finished within 15 min, but only cost ~1 RMB (10 cents).

Sensitive antibody fluorescence immunosorbent assay (SAFIA) for rapid on-site detection on avian influenza virus H9N2 antibody.

Avian influenza virus (AIV) is a serious zoonotic disease causing severe damages to both poultry industry and human health. To rapidly detect AIV on-site with high sensitivity and accuracy, we design sensitive antibody fluorescence immunosorbent assay (SAFIA) on AIV H9N2 antibody. In SAFIA, hemagglutinin (HA1) protein coated sample chamber specifically binds targets but remarkably reduces non-specific absorption; Protein L coated polystyrene microsphere captures target through secondary antibody to significantly amplify the fluorescence signal; and a portable fluorescence counter automatically measures the fluorescence spot density for AIV H9N2 antibody detection. Proved by practical applications, SAFIA could probe AIV H9N2 antibody in high sensitivity and selectivity, and distinguish positive and negative serum samples in high accuracy. Additionally, SAFIA can rapidly detect AIV H9N2 antibody at room temperature only requiring simple operations as well as cost-effective and compact devices. Therefore, SAFIA is a potential new-generation tool in rapid on-site testing for agricultures.

PhaseRMiC: phase real-time microscope camera for live cell imaging.

We design a novel phase real-time microscope camera (PhaseRMiC) for live cell phase imaging. PhaseRMiC has a simple and cost-effective configuration only consisting of a beam splitter and a board-level camera with two CMOS imaging chips. Moreover, integrated with 3-D printed structures, PhaseRMiC has a compact size of 136×91×60 mm3, comparable to many commercial microscope cameras, and can be directly connected to the microscope side port. Additionally, PhaseRMiC can be well adopted in real-time phase imaging proved with satisfied accuracy, good stability and large field of view. Considering its compact and cost-effective device design as well as real-time phase imaging capability, PhaseRMiC is a preferred solution for live cell imaging.

Amplification-free smartphone-based attomolar HBV detection.

Classical gold standard HBV detection relies on expensive devices and complicated procedures, thus is always restricted in large-scale hospitals and centers for disease control and prevention. To extend HBV detection to primary clinics especially in underdeveloped areas, we design amplification-free smartphone-based attomolar HBV detecting technique based on single molecule sensing. Verified by synthesized HBV target DNA, this technique reaches a detection limit at attomolar concentration (100 aM); and verified by 110 clinical samples, it also reaches a rather high sensitivity of 104 copy/mL (≈2000 IU/mL) with a high accuracy of 93.64% certificated by gold standard HBV detecting devices. Besides, this technique can quantify HBV viral load in 70 min only using portable and inexpensive devices as well as simple operations. Because of its cost-effective, field-portable and operable design, highly sensitive and selective detecting capability and wireless data connectivity, this technique can be potentially used in mobile HBV diagnoses and share HBV epidemic information especially in resource limited situations.

On-site quantitative Hg2+ measurements based on selective and sensitive fluorescence biosensor and miniaturized smartphone fluorescence microscope.

Mercury is a bio-accumulative and toxic pollutant causing severe damages to human health and environment. Since Hg2+ is the most stable form of mercury, selective and sensitive Hg2+ detection is required. Though classical approaches can realize accurate Hg2+ detection, the complicated instruments and the time-consuming operations inevitably limit their on-site applications. Here, we design a smart Hg2+ detection approach using the fluorescence biosensor, the smartphone fluorescence microscope and the smartphone application for Hg2+ on-site detection. Based on the thymine-Hg2+-thymine coordination chemistry, a selective and sensitive fluorescence biosensor is designed for capturing Hg2+ in aqueous solution; besides, a miniaturized smartphone fluorescence microscope for fluorescence signal collection and an image processing application for quantitative Hg2+ measurements are constructed. A highly specific detection of Hg2+ with a linear relation between 1 nM and 1 µM with a limit of detection of 1 nM is obtained using the smart Hg2+ detection approach. Considering it can realize selective and sensitive quantitative Hg2+ measurements in high precision with simple operations and cost-effective system, it is believed the proposed smart Hg2+ detection approach owns great potentials in Hg2+ detection for routine uses at home and in the field.

On-site cell concentration and viability detections using smartphone based field-portable cell counter.

We designed a smartphone based field-portable cell counter combining the smartphone microscope for bright-field image recording and the smartphone application for automatically cell recognition, counting and analysis. To our best knowledge, it is the first time that a smartphone based cell counter can distinguish and count both live and dead cells simultaneously. Compared to the results obtained by hemocytometer, commercial cell counter and flow cytometer, the proposed device was proved to detect cell concentration and viability accurately within the application range between 105 cells/mL and 107 cells/mL. Though multiple fields of view were measured to increase the sampling amount for error reduction, the whole operations including image recording and processing can still be finished rapidly. Moreover, the proposed device is cost-effective with small size of 170 mm × 113 mm × 168 mm containing a built-in power supply. Considering its advantages as high accuracy, fast speed, low cost, long battery life and compact configuration, it is believed the proposed device is a potential tool applied in on-site cell analysis.

Sunlight based handheld smartphone spectrometer.

We present a sunlight based handheld smartphone spectrometer. The device first gathers the sunlight to pass through the sample, and then the transmitted light illuminates on a grating to generate spectrum finally recorded by the smartphone monochrome camera. All the optical elements are assembled with the smartphone to integrate a handheld device with the size of 140.2 mm × 67.4 mm × 80.5 mm. Besides, a smartphone application is also developed for automatic spectral calibration, detection, analysis and display. Compared to the white light emitting diode and the halogen lamp, the sunlight has more uniform distribution covering the entire visible spectral range; and the proposed device also avoids the bulky sizes of those broadband light sources. Additionally, the monochrome camera is used instead of the color camera not only to pursue a high spectral resolution as 0.276 nm/pixel but also to avoid the color overlapping. We demonstrate the device capability on detecting avian influenza virus H7N9 and porcine circovirus type 2 antibodies, proving the device has rather high sensitivity similar to the commercial microplate reader. Considering its advantages as compact size, high spectral resolution and detecting sensitivity, it is believed the proposed sunlight based handheld smartphone spectrometer is potential to be broadly applied in on-site detections.

Handheld Inkjet Printing Paper Chip Based Smart Tetracycline Detector.

Tetracycline is widely used as medicine for disease treatments and additives in animal feeding. Unfortunately, the abuse of tetracycline inevitably causes tetracycline residue in animal-origin foods. Though classical methods can detect tetracycline in high sensitivity and precision, they often rely on huge and expensive setups as well as complicated and time-consuming operations, limiting their applications in rapid and on-site detection. Here, we propose a handheld inkjet printing paper chip based smart tetracycline detector: tetracycline can be determined by inkjet printing prepared paper chip based enzyme-linked immunosorbent assay (ELISA) with the advantages of high sensitivity, excellent specificity and low cost; moreover, a smartphone based paper chip reader and application is designed for automatically determining tetracycline with simple operations, high precision and fast speed. The smart tetracycline detector with a compact size of 154 mm × 80 mm × 50 mm and self-supplied internal power can reach a rather low detection limit of ~0.05 ng/mL, as proved by practical measurements. It is believed the proposed handheld inkjet printing paper chip based smart tetracycline detector is a potential tool in antibiotic sensing for routine uses at home and on-site detection in the field.

Label-free monitoring of cell death induced by oxidative stress in living human cells using terahertz ATR spectroscopy.

We demonstrated that attenuated total reflectance terahertz time-domain spectroscopy (ATR THz-TDS) is able to monitor oxidative stress response of living human cells, which is proven in this work that it is an efficient non-invasive, label-free, real-time and in situ monitoring of cell death. Furthermore, the dielectric constant and dielectric loss of cultured living human breast epithelial cells, and along with their evolution under oxidative stress response induced by high concentration of H2O2, were quantitatively determined in the work. Our observation and results were finally confirmed using standard fluorescence-labeled flow cytometry measurements and visible fluorescence imaging.

Smartphone based hand-held quantitative phase microscope using the transport of intensity equation method.

In order to realize high contrast imaging with portable devices for potential mobile healthcare, we demonstrate a hand-held smartphone based quantitative phase microscope using the transport of intensity equation method. With a cost-effective illumination source and compact microscope system, multi-focal images of samples can be captured by the smartphone's camera via manual focusing. Phase retrieval is performed using a self-developed Android application, which calculates sample phases from multi-plane intensities via solving the Poisson equation. We test the portable microscope using a random phase plate with known phases, and to further demonstrate its performance, a red blood cell smear, a Pap smear and monocot root and broad bean epidermis sections are also successfully imaged. Considering its advantages as an accurate, high-contrast, cost-effective and field-portable device, the smartphone based hand-held quantitative phase microscope is a promising tool which can be adopted in the future in remote healthcare and medical diagnosis.