Single-exposure multi-wavelength optical diffraction tomography based on space-angle dual multiplexing holography.

We present a space-angle dual multiplexing holographic recording system for realizing single-exposure multi-wavelength optical diffraction tomographic (ODT) imaging. This system is achieved by combining the principle of single-exposure multi-wavelength holographic imaging technique based on angle-division multiplexing with the principle of single-exposure ODT imaging technique based on microlens array multi-angle illuminations and space-division multiplexing. Compared with the existing multi-wavelength ODT imaging methods, it enables the holographic recording of all the diffraction tomography information of a measured specimen at multiple illumination wavelengths in a single camera exposure without any scan mechanism. Using our proposed data processing method, the multi-wavelength three-dimensional (3D) refractive index tomograms of a specimen can be eventually reconstructed from single recorded multiplexing hologram. Experimental results of a static polystyrene bead and a living C. elegans worm demonstrate the feasibility of this system.

Simple system for realizing single-shot ultrafast sequential imaging based on spatial multiplexing in-line holography.

We present a simple system for realizing single-shot ultrafast sequential imaging based on spatial multiplexing in-line holography. In this system, we propose to combine a specially designed mini-reflector delay-line array with digital in-line holography. The former including a group of adjustable mini-reflectors can easily generate an array of probe sub-pulses that can be controlled independently in the propagation direction and time delays. The object beams formed by the different sub-pulses will propagate and fall on different recording regions of the image sensor to generate a single-shot spatial-multiplexing in-line hologram. The geometry of the digital in-line holography can simplify the complexity of the system and enable complex amplitude imaging. In addition, the time resolution of this system is limited only by the pulse duration, which allows this system to study the dynamic processes with the femtosecond order. In an experiment about the laser-induced air plasma, our proposed system achieves nine frames sequential holographic images with the frame rate of 7.5 trillion frames per second (Tfps).

Cylindrical wave-based off-axis digital holography with long field of view.

We present a new, to the best of our knowledge, type of off-axis digital holographic imaging method with a long field of view (FOV). In the method, the pre-magnification recording geometry is realized by a cylindrical lens (CL) or cylindrical beam instead of a conventional objective or spherical beam in traditional off-axis digital holography (DH). At the same time, the reference beam is replaced by a divergent cylindrical beam. Theoretical analysis and experiments have justified that, in off-axis DHs, the adoption of the cylindrical beams can realize a one-dimensional pre-magnification of the object beam only in the off-axis direction to satisfy the bandwidth constraint, and at the same time the FOV of the reconstructed image in the orthogonal direction can remain unaffected. In comparison with existing off-axis DHs, this cylindrical wave-based DH (CWDH) method has a distinct advantage in expanding the FOV of the reconstructed image. The FOV feature of the CWDH makes it especially suitable for applications that require a long FOV such as imaging samples in microfluidic channels.

Polarization holographic microscope slide for birefringence imaging of anisotropic samples in microfluidics.

Birefringence is an important optical property of anisotropic materials arising from anisotropies of tissue microstructures. Birefringence parameters have been found to be important to understand optical anisotropic architecture of many materials and polarization imaging has been applied in many researches in the field of biology and medicine. Here, we propose a scheme to miniaturize a double-channel polarization holographic interferometer optics to create a polarization holographic microscope slide (P-HMS) suitable for integrating with microfluidic lab-on-a-chip (LoC) systems. Based on the P-HMS combined with a simple reconstruction algorithm described in the paper, we can not only simultaneously realize holographic imaging of two orthogonal polarization components of dynamic samples in a microfluidic channel but also quantitative measurement of 2D birefringence information, both including the birefringence phase retardation and optic-axis orientation. This chip interferometer allows for off-axis double-channel polarization digital holographic recording using only a single illumination beam without need of any beam splitter or mirror. Its quasi-common path configuration and self-aligned design also make it tolerant to vibrations and misalignment. This work about the P-HMS could play a positive role in promoting the application of birefringence imaging in microfluidic LoC technology.

Single-shot ultrafast sequential holographic imaging with high temporal resolution and a large field of view.

A compact system for single-shot sequential holographic imaging (SSSHI) with high temporal resolution and a large field of view is proposed. In this system, a specially designed sequence pulse train generator with a group of diffractive gratings inserted is adopted to simultaneously generate the probe pulse train and the reference pulse train required for recording a single-shot spatial frequency division multiplexing hologram. The system successfully overcomes the walk-off effect of the ultrashort pulse laser in SSSHI and, hence, effectively avoids the influence of the short coherence of ultrashort pulses on the spatial resolution (or field of view) of SSSHI; the complexity of the system and the difficulty in the precise synchronous alignment of the probe and the reference pulses also can be greatly reduced. An experimental setup of the system was constructed, and a SSSHI of dynamical air plasmas induced by a femtosecond pulse laser is successfully realized.

Single-shot quantitative birefringence microscopy for imaging birefringence parameters.

A method for realizing 2D single-shot measurements of birefringence parameters (including both retardation and optic axis orientation) of anisotropic materials using a simple recording setup and an efficient processing algorithm is proposed. The recording setup can be built simply by inserting a circular polarizer and a polarization beam splitter, respectively, in the object path and reference path of a conventional off-axis holographic imaging system, with no need for other adjustments. An algorithm for quantitatively retrieving the birefringence parameters from one single-shot hologram is proposed and demonstrated, in which a new quantity describing the birefringence, called complex birefringence parameter, is introduced, and a set of formulas used to extract the birefringence parameters is derived. Some experimental results are given for demonstrating the feasibility of the method that reveal that the method may provide another effective approach for investigating the birefringence properties of dynamic anisotropic materials, especially the birefringence induced by ultrafast pulse lasers.

A 2.5 mW/ch, 50 Mcps, 10-Analog Channel, Adaptively Biased Read-Out Front-End IC With Low Intrinsic Timing Resolution for Single-Photon Time-of-Flight PET Applications With Time-Dependent Noise Analysis in 90 nm CMOS.

This paper presents a 10-channel time-of-flight application-specific integrated circuit (ASIC) for positron emission tomography in a 90 nm standard CMOS process. To overcome variations in channel-to-channel timing resolution caused by mismatch and process variations, adaptive biases and a digital-to-analog converter (DAC) are utilized. The main contributions of this work are as follows. First, multistage architectures reduce the total power consumption, and detection bandwidths of analog preamplifiers and comparators are increased to 1 and 1.5 GHz, respectively, relative to those in previous studies. Second, a total intrinsic electronic timing resolution of 9.71 ps root-mean-square (RMS) is achieved (13.88 ps peak and 11.8 ps average of the 10 channels in 5 ASICs). Third, the proposed architecture reduces variations in channel-to-channel timing resolution to 2.6 bits (equivalent to 4.17 ps RMS) by calibrating analog comparator threshold levels. A 181.5 ps full-width-at-half-maximum timing resolution is measured with an avalanche photo diode and a laser setup. The power consumption is 2.5 mW using 0.5 and 1.2 V power supplies. The proposed ASIC is implemented in a 90 nm TSMC CMOS process with a total area of 3.3 mm × 2.7 mm.

A low-power bio-potential acquisition system with flexible PDMS dry electrodes for portable ubiquitous healthcare applications.

This work describes a bio-potential acquisition system for portable ubiquitous healthcare applications using flexible polydimethylsiloxane dry electrodes (FPDEs) and a low-power recording circuit. This novel FPDE used Au as the skin contact layer, which was made using a CO2 laser and replica method technology. The FPDE was revised from a commercial bio-potential electrode with a conductive snap using dry electrodes rather than wet electrodes that proposed reliable and robust attachment for the purpose of measurement, and attaching velcro made it wearable on the forearm for bio-potential applications. Furthermore, this study proposes a recording device to store bio-potential signal data and provides portability and low-power consumption for the proposed acquisition system. To acquire differential bio-potentials, such as electrocardiogram (ECG) signals, the proposed recording device includes a low-power front-end acquisition chip fabricated using a complementary metal-oxide-semiconductor (CMOS) process, a commercial microcontroller (MSP430F149), and a secure digital (SD) card for portable healthcare applications. The proposed system can obtain ECG signals efficiently and are comfortable to the skin. The power consumption of the system is about 85 mW for continuous working over a 3 day period with two AA batteries. It can also be used as a compact Holter ECG system.

An efficient micro control unit with a reconfigurable filter design for wireless body sensor networks (WBSNs).

In this paper, a low-cost, low-power and high performance micro control unit (MCU) core is proposed for wireless body sensor networks (WBSNs). It consists of an asynchronous interface, a register bank, a reconfigurable filter, a slop-feature forecast, a lossless data encoder, an error correct coding (ECC) encoder, a UART interface, a power management (PWM), and a multi-sensor controller. To improve the system performance and expansion abilities, the asynchronous interface is added for handling signal exchanges between different clock domains. To eliminate the noise of various bio-signals, the reconfigurable filter is created to provide the functions of average, binomial and sharpen filters. The slop-feature forecast and the lossless data encoder is proposed to reduce the data of various biomedical signals for transmission. Furthermore, the ECC encoder is added to improve the reliability for the wireless transmission and the UART interface is employed the proposed design to be compatible with wireless devices. For long-term healthcare monitoring application, a power management technique is developed for reducing the power consumption of the WBSN system. In addition, the proposed design can be operated with four different bio-sensors simultaneously. The proposed design was successfully tested with a FPGA verification board. The VLSI architecture of this work contains 7.67-K gate counts and consumes the power of 5.8 mW or 1.9 mW at 100 MHz or 133 MHz processing rate using a TSMC 0.18 µm or 0.13 µm CMOS process. Compared with previous techniques, this design achieves higher performance, more functions, more flexibility and higher compatibility than other micro controller designs.

An asynchronous multi-sensor micro control unit for wireless body sensor networks (WBSNs).

In this work, an asynchronous multi-sensor micro control unit (MCU) core is proposed for wireless body sensor networks (WBSNs). It consists of asynchronous interfaces, a power management unit, a multi-sensor controller, a data encoder (DE), and an error correct coder (ECC). To improve the system performance and expansion abilities, the asynchronous interface is created for handshaking different clock domains between ADC and RF with MCU. To increase the use time of the WBSN system, a power management technique is developed for reducing power consumption. In addition, the multi-sensor controller is designed for detecting various biomedical signals. To prevent loss error from wireless transmission, use of an error correct coding technique is important in biomedical applications. The data encoder is added for lossless compression of various biomedical signals with a compression ratio of almost three. This design is successfully tested on a FPGA board. The VLSI architecture of this work contains 2.68-K gate counts and consumes power 496-µW at 133-MHz processing rate by using TSMC 0.13-µm CMOS process. Compared with the previous techniques, this work offers higher performance, more functions, and lower hardware cost than other micro controller designs.

Real-time telemetry system for amperometric and potentiometric electrochemical sensors.

A real-time telemetry system, which consists of readout circuits, an analog-to-digital converter (ADC), a microcontroller unit (MCU), a graphical user interface (GUI), and a radio frequency (RF) transceiver, is proposed for amperometric and potentiometric electrochemical sensors. By integrating the proposed system with the electrochemical sensors, analyte detection can be conveniently performed. The data is displayed in real-time on a GUI and optionally uploaded to a database via the Internet, allowing it to be accessed remotely. An MCU was implemented using a field programmable gate array (FPGA) to filter noise, transmit data, and provide control over peripheral devices to reduce power consumption, which in sleep mode is 70 mW lower than in operating mode. The readout circuits, which were implemented in the TSMC 0.18-µm CMOS process, include a potentiostat and an instrumentation amplifier (IA). The measurement results show that the proposed potentiostat has a detectable current range of 1 nA to 100 µA, and linearity with an R2 value of 0.99998 in each measured current range. The proposed IA has a common-mode rejection ratio (CMRR) greater than 90 dB. The proposed system was integrated with a potentiometric pH sensor and an amperometric nitrite sensor for in vitro experiments. The proposed system has high linearity (an R2 value greater than 0.99 was obtained in each experiment), a small size of 5.6 cm × 8.7 cm, high portability, and high integration.

Co-delivery of anti-vascular endothelial growth factor siRNA and doxorubicin by multifunctional polymeric micelle for tumor growth suppression.

Nonviral gene carriers composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. We have developed multifunctional nanomicelles for both drug and gene delivery application. Polyethylenimine (PEI) was modified by grafting stearic acid (SA) and further formulated to polymeric micelles (PEI-SA) with positive surface charge for gene delivery evaluation. Our results showed that PEI-SA micelles provided high siRNA binding efficiency and exhibited low cytotoxicity compared with unmodified PEI. siRNA delivered by PEI-SA carriers also demonstrated significantly higher cellular uptake efficiency and stability even in the presence of serum proteins when compared with free siRNA. The post-transcriptional gene silencing efficiency was greatly improved by the polyplex formulated by 10k PEI-SA/siRNA. In the animal intratumoral model study, the combination of co-delivering doxorubicin and vascular endothelial growth factor (VEGF) siRNA delivered by PEI-SA micelles showed a promising effect on anti-tumor growth. The amphiphilic structure of PEI-SA micelles provides advantages for multifunctional tasks; such that hydrophilic shell modified with cationic charges can electrostatically interact with DNA or siRNA, and hydrophobic core can serve as a payload for hydrophobic drugs, making it truly a promising multifunctional vehicle for both genetic and chemotherapy application.

Polymeric micelles comprising stearic acid-grafted polyethyleneimine as nonviral gene carriers.

Non-viral vectors composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. Among some of the cationic polymers, polyethyleneimine (PEI) possess high pH-buffering capacity that can provide protection to nucleotides from acidic degradation and promotes endosomal and lysosomal release. However, it has been reported that cytotoxicity of PEI depends on the molecular weight of the polymer. Hence modifications of PEI structure for clinical application have been developed in order to reduce the cytotoxicity, or improve the insufficient transfection efficiency of lower molecular weight PEI. In this study, 10 k PEI was modified by grafting stearic acid (SA) and formulated to polymer micelles with positive surface charge and evaluated for pDNA delivery. The amine group on PEI was crosslinked with the carboxylic group of stearic acid by 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide (EDC) as linker. PEI-SA micelles were then prepared using oil in water (o/w) solvent evaporation method. The success of PEI-SA conjugation structure was confirmed with 1H NMR. The average diameter and zeta potential determined by photon correlation spectroscopy was 149.6 +/- 1.2 nm and 64.1 +/- 1.5 mV, respectively. These self-assemble positive charge micelles showed effective binding to pDNA for transfection. PEI-SA micelles exhibited lower cytotoxicity compared to that of PEI only, while flow cytometry analysis revealed PEI-SA/pEGFP complex provided 62% high EGFP expression. Luciferase activity also showed high transfection efficiency of PEI-SA micelles for weight ratio above 4.5 that was comparable to PEI only. These results demonstrated that stearic acid grafted PEI micelles can provide high transfection efficiency comparable to unmodified PEI, and exhibit low cytotoxicity. Stearic acid grafted PEI micelles can be promising polymer carriers in genetic therapy.

Cell uptake and intracellular visualization using quantum dots or nuclear localization signal-modified quantum dots with gold nanoparticles as quenchers.

Understanding and controlling the interactions between nanoscale objects and living cells is of great importance for diagnostic imaging and therapeutic applications. Quantum dots (QDs) have remarkable optical characteristics, such as uniquely feature bright, photostable, tunable and narrow fluorescence emissions, as well as broad absorption spectra. Here we report a platform of using quantum dots to investigate the cell uptake and the interactions between nanoscale objects and cells. QDs are uptaken by BHK cells easily through endocytosis. We could clearly differentiate the QDs outside the cell or inside the cell by quenching the QDs with similar sized gold nanoparticles and reduce the noise of fluorescent image. Microscopic images show that QDs are homogeneously distributed within the whole cell except the nucleus. However, unmodified QDs could not penetrate the nuclear membrane and move into the nucleus. Coupling QDs with Nuclear Localization Signal (NLS, CGGGPKKKRKVGG) can significantly enhance the translocation amount of QDs into the cell and cell nucleus. This method combined with microscopy imaging system can visualize the particle delivery routes and provide valuable information in the drug/gene delivery and tumor diagnosis.

Wide dynamic range CMOS potentiostat for amperometric chemical sensor.

Presented is a single-ended potentiostat topology with a new interface connection between sensor electrodes and potentiostat circuit to avoid deviation of cell voltage and linearly convert the cell current into voltage signal. Additionally, due to the increased harmonic distortion quantity when detecting low-level sensor current, the performance of potentiostat linearity which causes the detectable current and dynamic range to be limited is relatively decreased. Thus, to alleviate these irregularities, a fully-differential potentiostat is designed with a wide output voltage swing compared to single-ended potentiostat. Two proposed potentiostats were implemented using TSMC 0.18-µm CMOS process for biomedical application. Measurement results show that the fully differential potentiostat performs relatively better in terms of linearity when measuring current from 500 pA to 10 uA. Besides, the dynamic range value can reach a value of 86 dB.

A power-efficient bio-potential acquisition device with DS-MDE sensors for long-term healthcare monitoring applications.

This work describes a power-efficient bio-potential acquisition device for long-term healthcare applications that is implemented using novel microelectromechanical dry electrodes (MDE) and a low power bio-potential processing chip. Using micromachining technology, an attempt is also made to enhance the sensing reliability and stability by fabricating a diamond-shaped MDE (DS-MDE) that has a satisfactory self-stability capability and superior electric conductivity when attached onto skin without any extra skin tissue injury technology. To acquire differential bio-potentials such as ECG signals, the proposed processing chip fabricated in a standard CMOS process has a high common mode rejection ratio (C.M.R.R.) differential amplifier and a 12-bit analog-to-digital converter (ADC). Use of the proposed system and integrate simple peripheral commercial devices can obtain the ECG signal efficiently without additional skin tissue injury and ensure continuous monitoring more than 70 hours with a 400 mAh battery.

Intracellular trafficking, metabolism and toxicity of current gene carriers.

Gene delivery remains to be a very challenging field to efficiently transport the therapeutic gene and to modulate proteins with the desired function at the target site. The physiochemical and biological barriers are the major hurdles that need to be considered, particularly when administered systematically, in order to optimize the therapeutic efficacy. Numerous modifications have been extensively investigated aiming to provide protection from the plasma degradation, enhancement of transfection, target specificity, and most importantly, minimizing the side effects such as cellular toxicity and immune response. This article provides a review with respect to the in vitro and in vivo toxicity, as well as cellular and physiological interactions with the gene delivery system composed from viral vectors, cationic lipids and polymers. Recent progress and development are also addressed, with promising results that may be further adopted for clinical use.

Involvement of cystic fibrosis transmembrane conductance regulator (CFTR) in the pathogenesis of hydrosalpinx induced by Chlamydia trachomatis infection.

BACKGROUND: Genital Chlamydia (C) trachomatis infection has been recognized as the single most common cause of pelvic inflammatory disease leading to severe tubal damage, ectopic pregnancy, infertility and hydrosalpinx. However, the mechanism underlying the formation of hydrosalpinx induced by C. trachomatis infection remains largely unknown. We performed this study to determine the involvement of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel that regulates epithelial electrolyte and fluid secretion, in hydrosalpinx fluid formation. METHODS: Western blot analysis was used to determine CFTR expression in the hydrosalpinges that were seen on the ultrasound scans of infertile assisted reproduction treatment patients. Correlation with C. trachomatis infection was done by testing patients' sera for C. trachomatis immunoglobulin G antibody titer using a Capita enzyme-linked immunosorbent assay based kit. CFTR involvement was further verified in a rat C. trachomatis infection model and confirmed using CFTR mutant (CFTR(tm1Unc)) mice. RESULTS: Here we report on the up-regulated expression of CFTR in the hydrosalpinx tissues of infertile patients with detectable serum levels of C. trachomatis antibody (immunoglobulin G). In a rat model, increased CFTR expression and fluid accumulation could be observed in the uterine horns infected with C. trachomatis elementary bodies, which was reversed by antibiotics treatment. In C. trachomatis-infected CFTR(tm1Unc) mice, however, no detectable fluid accumulation was observed. CONCLUSION: These findings suggest the involvement of CFTR in the pathogenesis of hydrosalpinx fluid formation and may provide grounds for a better treatment strategy to improve assisted reproduction treatment outcome in infertile patients with hydrosalpinx.

Involvement of cystic fibrosis transmembrane conductance regulator in infection-induced edema.

Abnormal fluid accumulation in tissues, including the life-threatening cerebral and pulmonary edema, is a severe consequence of bacteria infection. Chlamydia (C.) trachomatis is an obligate intracellular gram-negative human pathogen responsible for a spectrum of diseases, causing tissue fluid accumulation and edema in various organs. However, the underlying mechanism for tissue fluid secretion induced by C. trachomatis and most of other infectious pathogens is not known. Here, we report that in mice C. trachomatis infection models, the expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP activated chloride channel, is up regulated together with increased cytokine release and tissue fluid accumulation that can be reversed by treatment with antibiotic specific for C. trachomatis and CFTR channel blocker. However, C. trachomatis infection cannot induce tissue edema in CFTRtm1Unc mutant mice. Administration of exogenous IL-1beta to mice mimics the C. trachomatis infection-induced CFTR upregulation, enhanced CFTR channel activity and fluid accumulation, further confirming the involvement of CFTR in infection-induced tissue fluid secretion.

Wireless thermal sensor network with adaptive low power design.

There is an increasing need to develop flexible, reconfigurable, and intelligent low power wireless sensor network (WSN) system for healthcare applications. Technical advancements in micro-sensors, MEMS devices, low power electronics, and radio frequency circuits have enabled the design and development of such highly integrated system. In this paper, we present our proposed wireless thermal sensor network system, which is separated into control and data paths. Both of these paths have their own transmission frequencies. The control path sends the power and function commands from computer to each sensor elements by 2.4GHz RF circuits and the data path transmits measured data by 2.4GHz in sensor layer and 60GHz in higher layers. This hierarchy architecture would make reconfigurable mapping and pipeline applications on WSN possibly, and the average power consumption can be efficiently reduced about 60% by using the adaptive technique.