Portable and Battery-Powered PCR Device for DNA Amplification and Fluorescence Detection.

Polymerase chain reaction (PCR) is a technique for nucleic acid amplification, which has been widely used in molecular biology. Owing to the limitations such as large size, high power consumption, and complicated operation, PCR is only used in hospitals or research institutions. To meet the requirements of portable applications, we developed a fast, battery-powered, portable device for PCR amplification and end-point detection. The device consisted of a PCR thermal control system, PCR reaction chip, and fluorescence detection system. The PCR thermal control system was formed by a thermal control chip and external drive circuits. Thin-film heaters and resistance temperature detectors (RTDs) were fabricated on the thermal control chip and were regulated with external drive circuits. The average heating rate was 32 °C/s and the average cooling rate was 7.5 °C/s. The disposable reaction chips were fabricated using a silicon substrate, silicone rubber, and quartz plate. The fluorescence detection system consisted a complementary metal-oxide-semiconductor (CMOS) camera, an LED, and mirror units. The device was driven by a 24 V Li-ion battery. We amplified HPV16E6 genomic DNA using our device and achieved satisfactory results.

Fluorescence quantification of intracellular materials at the single-cell level by an integrated dual-well array microfluidic device.

We present an integrated microfluidic device for quantifying intracellular materials at the single-cell level. This device combines a dual-well structure and a microfluidic control system. The dual-well structure includes capture wells (20 µm in diameter) for trapping a single cell and reaction wells (200 µm in diameter) for confining reagents. The control system enables a programmable procedure for single-cell analysis. This device achieves highly efficient trapping of single cells, overcoming the Poisson distribution, while affording sufficient biochemical reagents for each isolated reactor. We successfully utilized the presented device to monitor the catalytic interaction between intracellular alkaline phosphatase enzyme and a fluorogenic substrate and to quantify the intracellular glucose concentration of a single K562 cell based on an external standard method. The results demonstrate the feasibility and convenience of our dual-well array microfluidic device as a practical single-cell research tool.

Polarization-independent directional coupler and polarization beam splitter based on asymmetric cross-slot waveguides.

The polarization dependence of a directional coupler (DC) based on asymmetric cross-slot waveguides is investigated. Due to structural birefringence, the coupling behaviors of the quasi-TE and quasi-TM modes in the DC vary with the waveguide geometry. A polarization-independent directional coupler (PIDC) and polarization beam splitter (PBS) are proposed by tailoring the ratio of the coupling length for quasi-TE and quasi-TM modes. The simulated results show that the coupling lengths of the designed PIDC and PBS are 8 and 28.25 µm, respectively. Both the PIDC and PBS show an insertion loss (IL) <0.7 dB on a bandwidth over 100 nm. The extinction ratios are ∼20 dB for PIDC and ∼14 dB for PBS. The fabrication-error tolerance of the practical devices is also discussed. In this study, we employ a commercial software tool for finite difference eigenmode and three-dimensional finite difference time domain methods to perform the numerical simulations.

A concise iterative method using the Bezier technique for baseline construction.

A novel approach, coined the Corner-Cutting method (CC, for short), is presented in this paper which affords the efficient construction of the baseline for analytical data streams. It was derived from techniques used in computer aided geometric design, a field established to produce curves and surfaces for the aviation and automobile industries. This corner-cutting technique provided a very efficient baseline calculation through an iterative process. Furthermore, a terminal condition was developed to make the process fully automated and truly non-parametric. Finally, we employed a Bezier curve to convert the iterating result into a smooth baseline solution. Compared to other iterative schemes used for baseline detection, our method was significantly efficient, easier to implement, and had a broader range of applications.

Fast and efficient silicon thermo-optic switching based on reverse breakdown of pn junction.

We propose and demonstrate a fast and efficient silicon thermo-optic switch based on reverse breakdown of the pn junction. Benefiting from the direct heating of silicon waveguide by embedding the pn junction into the waveguide center, fast switching with on/off time of 330 and 450 ns and efficient thermal tuning of 0.12 nm/mW for a 20 µm radius microring resonator are achieved, indicating a high figure of merit of only 8.8 mW·µs. The results here show great potential for application in the future optical interconnects.

High-speed silicon modulator with band equalization.

Electro-optic modulation up to 70 Gbit/s has been demonstrated using a silicon Mach-Zehnder modulator with a bias voltage of -1.5 V. In a wide frequency range from DC, an increasing input impedance of the modulator was designed to equalize its electro-optic frequency response. Without a bias voltage, the 3 dB bandwidth was measured as 35 GHz and it is predicted to be as high as 55 GHz at -3 V bias. Frequency responses of the modulator operated with counter-propagating waves were tested to verify the proposed prediction model.

Design of polarization-independent adiabatic splitters fabricated on silicon-on-insulator substrates.

A novel design for a polarization-independent SOI-based 2 × 2 3-dB adiabatic splitter with sub-micron-scale dimensions is proposed and modeled. To achieve slow and smooth mode evolution, a structure with simultaneous tapering of velocity and coupling is used. To reduce the adiabatic region length by adjusting the gap separation, the coupling strengths of TE and TM polarizations as a function of the gap value are analyzed. For both polarizations, a high uniformity within ± 0.2dB over a broad bandwidth from 1520 to 1650 nm is achieved with a 300-µm-long adiabatic region.

High-speed, low-loss silicon Mach-Zehnder modulators with doping optimization.

We demonstrate a high-speed silicon Mach-Zehnder modulator (MZM) with low insertion loss, based on the carrier depletion effect in a lateral PN junction. A 1.9 dB on-chip insertion loss and a VπLπ < 2 V·cm were achieved in an MZM with a 750 µm-long phase shifter by properly choosing the doping concentration and precisely locating the junction. High-speed modulations up to 45-60 Gbit/s have been demonstrated with an additional 1.6 dB optical loss, indicating a total insertion loss of 3.5 dB. A high extinction ratio of 7.5 dB was also realized at the bit rate of 50 Gbit/s with an acceptable insertion loss of 6.5 dB.

Low cross-talk 2 × 2 silicon electro-optic switch matrix with a double-gate configuration.

In this study, a low cross-talk 2 × 2 silicon electro-optic switch matrix based on a double-gate configuration is proposed and experimentally demonstrated. The switch matrix consists of four Mach-Zehnder-based 2 × 2 switching elements with 400 µm long modulation arms. Low cross-talk values of -31 and -43 dB are, respectively, obtained for the "cross" and "bar" states over a 40 nm wide wavelength range around 1550 nm. The values for the total steady-state power consumption of the "cross" and "bar" states are 40.8 and 19.1 mW, respectively.

Nonblocking 4×4 silicon electro-optic switch matrix with push-pull drive.

A compact rearrangeable nonblocking 4×4 silicon electro-optic switch matrix based on a Spanke-Benes network is proposed and fabricated by a 0.18 µm standard commercial complementary metal-oxide semiconductor line. By respectively modulating the two modulation arms with a push-pull drive, a cross talk (CT) of less than -18 dB is obtained for the switching element with 150-µm-long modulation arms. The total steady-state power consumption of the switch matrix ranges from 4.46 to 35.92 mW for different routing states. The CT values of the routing state with the minimum and maximum power consumptions are less than -19 dB and less than -12 dB, respectively.

Compact and low-loss silicon power splitter based on inverse tapers.

A compact, low-loss, optical power splitter based on inverse tapers is proposed and fabricated on a silicon-on-insulator platform. High efficiency mode evolution between the fundamental mode of the input waveguide and the super mode of the output waveguides is realized using optimized tapers. A 1×4 splitter with insertion loss lower than 0.4 dB and uniformity better than 0.68 dB in a wavelength range from 1510 to 1550 nm are demonstrated within a footprint of only ~75 µm(2). These properties are very promising for ultrahigh density photonic integration applications.

Two-mode multiplexer and demultiplexer based on adiabatic couplers.

A two-mode (de)multiplexer based on adiabatic couplers is proposed and experimentally demonstrated. The experimental results are in good agreement with the simulations. An ultralow mode cross talk below -36 dB and a low insertion loss of about 0.3 dB over a broad bandwidth from 1500 to 1600 nm are measured. The design is also fabrication-tolerant, and the insertion loss can be further improved in the future.

Silicon-on-insulator-based adiabatic splitter with simultaneous tapering of velocity and coupling.

We propose and experimentally demonstrate a 2×2 3 dB adiabatic splitter based on silicon-on-insulator technology, with simultaneous tapering of the phase velocity and coupling. The advantages of the proposed splitter are indicated by analyzing the effective index evolution of the system modes and comparing them with the simulated performances. The experimental results are in good agreement with the simulations. Over the 100 nm wavelength range measured, the output uniformity is better than 0.2 dB. A low and flat excess loss of about 0.3 dB per splitter is obtained, with a variation below 0.2 dB.

Mach-Zehnder-based five-port silicon router for optical interconnects.

We propose and fabricate a five-port silicon optical router based on Mach-Zehnder interferometer switches. Only 10 switching elements and five low-loss waveguide crossings are required in our design. Through thermal control of the switching network, we successfully demonstrate 20 possible I/O paths of the five-port optical router at a data transmission rate of 32 Gb/s. The results here show great potential for application in ultrahigh-capacity optical interconnects.

Multiplex single-cell droplet PCR with machine learning for detection of high-risk human papillomaviruses.

High-risk human papillomavirus (HPV) testing can significantly decline the incidence and mortality of cervical cancer. Microfluidic technology provides an effective method for accurate detection of high-risk HPV by utilizing multiplex single-cell droplet polymerase chain reaction (PCR). However, current strategies are limited by low-integration microfluidic chip, complex reagent system, expensive detection equipment and time-consuming droplet identification. Here, we developed a novel multiplex droplet PCR method that directly detected high-risk HPV sequences in single cells. A multiplex microfluidic chip integrating four flow-focusing structures was designed for one-step and parallel droplet preparation. Using single-cell droplet PCR, multi-target sequences were detected simultaneously based on a monochromatic fluorescence signal. We applied machine learning to automatically identify the large populations of single-cell droplets with 97% accuracy. HPV16, 18 and 45 sequences were sensitively detected without cross-contamination in mixed CaSki and Hela cells. The approach enables rapid and reliable detection of multi-target sequences in single cells, making it powerful for investigating cellular heterogeneity related to cancer diagnosis and treatment.

High speed silicon Mach-Zehnder modulator based on interleaved PN junctions.

A high speed silicon Mach-Zehnder modulator is proposed based on interleaved PN junctions. This doping profile enabled both high modulation efficiency of V(π)L(π) = 1.5~2.0 V·cm and low doping-induced loss of ~10 dB/cm by applying a relatively low doping concentration of 2 × 10(17) cm(-3). High speed operation up to 40 Gbit/s with 7.01 dB extinction ratio was experimentally demonstrated with a short phase shifter of only 750 µm.

25 Gbit/s silicon microring modulator based on misalignment-tolerant interleaved PN junctions.

A high-speed depletion-mode silicon-based microring modulator with interleaved PN junctions optimized for high modulation efficiency and large alignment tolerance is demonstrated. It is fabricated using standard 0.18 µm complementary metal-oxide-semiconductor processes and provides low V(π)L(π)s of 0.68 V·cm to 1.64 V·cm with a moderate doping concentration of 2 × 10(17) cm(-3). The measured modulation efficiency decreases by only 12.4% under ± 150 nm alignment errors. 25 Gbit/s non-return-zero modulation with a 4.5 dB extinction ratio is experimentally realized at a peak-to-peak driving voltage of 2 V, demonstrating the excellent performance of the novel doping profile.

High-speed silicon modulator based on cascaded microring resonators.

A high-speed silicon modulator based on cascaded double microring resonators is demonstrated in this paper. The proposed modulator experimentally achieved 40 Gbit/s modulation with an extinction ratio of 3.9 dB. Enhancement of the modulator achieves with an ultra-high optical bandwidth of 0.41 nm, corresponding to 51 GHz, was accomplished by using cascaded double ring structure. The described modulator can provides an ultra-high-speed optical modulation with a further improvement in electrical bandwidth of the device.

Design and fabrication of a photonic crystal channel drop filter based on an asymmetric silicon-on-insulator slab.

We report on the design and fabrication of a photonic crystal (PC) channel drop filter based on an asymmetric silicon-on-insulator (SOI) slab. The filter is composed of two symmetric stick-shape micro-cavities between two single-line-defect (W1) waveguides in a triangular lattice, and the phase matching condition for the filter to improve the drop efficiency is satisfied by modifying the positions and radii of the air holes around the micro-cavities. A sample is then fabricated by using electron beam lithography (EBL) and inductively coupled plasma (ICP) etching processes. The measured Q factor of the filter is about 1140, and the drop efficiency is estimated to be 73% +/- 5% by fitting the transmission spectrum.

One step DNA amplification of mammalian cells in picoliter microwell arrays.

We developed a strategy for direct DNA amplification of single cells on a PEG-modified silica chip with 30 600 picoliter-sized microwells. HPV-positive cells in heterogeneous populations were successfully detected with high accuracy sensitivity as high as single copy.