A lab-on-disc centrifugal microfluidic system for ultraprecise plasma separation.

As the medical community puts forward higher requirements for the speed and convenience of disease diagnosis, point-of-care testing has become a hot research topic to overcome various kinds of healthcare problems. Blood test is considered to be highly sensitive and accurate in clinical diagnosis. However, conventional plasma separation system tends to be bulky and needs professional operations. Moreover, imprecise separation may cause residual biochemical substances such as blood cells to affect the detection results. In this work, to solve these problems, we designed a portable centrifugal microfluidic platform for automatic, rapid and ultraprecise blood separation. The disc consists of multichambers and multi-microchannels where a plasma reservoir and a cell reservoir are connected to each other and collinear with the center of the circle. This structure overcomes the weakness of low separation efficiency (when hematocrit increases) under the traditional blood separation structure (bifurcation structure). As a result, the proposed system achieved 99.9% plasma purity, 99.9% separation efficiency (with a blood hematocrit of 48%) and 32.5% plasma recovery rate in the 50s, which provides a strong guarantee for rapid blood diagnosis and analysis, especially in areas where medical resources are limited.

Application of centrifugal microfluidics in immunoassay, biochemical analysis and molecular diagnosis.

Rapid diagnosis plays a vital role in daily life and is effective in reducing treatment costs and increasing curability, especially in remote areas with limited availability of resources. Among the various common methods of rapid diagnosis, centrifugal microfluidics has many unique advantages, such as less sample consumption, more precise valve control for sequential loading of samples, and accurately separated module design in a microfluidic network to minimize cross-contamination. Therefore, in recent years, centrifugal microfluidics has been extensively researched, and it has been found to play important roles in biology, chemistry, and medicine. Here, we review the latest developments in centrifugal microfluidic platforms in immunoassays, biochemical analyses, and molecular diagnosis, in recent years. In immunoassays, we focus on the application of enzyme-linked immunosorbent assay (ELISA); in biochemical analysis, we introduce the application of plasma and blood cell separation; and in molecular diagnosis, we highlight the application of nucleic acid amplification tests. Additionally, we discuss the characteristics of the methods under each platform as well as the enhancement of the corresponding performance parameters, such as the limit of detection, separation efficiency, etc. Finally, we discuss the limitations associated with the existing applications and potential breakthroughs that can be achieved in this field in the future.

Surface Hydrophilic Modification for Chip of Centrifugal Microfluidic Immunoassay System.

The surface of a centrifugal microfluidic immunoassay system chip such as polymethyl methacrylate (PMMA) is often hydrophobic, which leads to problems such as poor liquid transfer efficiency and easy-to-block siphon channels, leading to bad fluid control. Therefore, surface hydrophilic modification for such chips is necessary to improve the rapidity and sensitivity of the system. Chemical modification is commonly used, but there is little research on the hydrophilic effect of different concentrations of hydrophilic reagents. According to function requirements for different microchannels of the chip (some only need to ensure the liquid can flow into the next chamber, and some also need to ensure the function of "closing the door" during immunoassay incubation), we explored the best combination of hydrophilic reagent and concentration through experiments. Firstly, three hydrophilic reagents were used for modification. Secondly, the hydrophilic effects of different reagents and concentrations were explored by contact angle test, the influence of different modification methods on liquid transfer efficiency was characterized by residual liquid calculation in the chamber. Finally, the effect of different hydrophilic reagents on absorbance was also tested. By experimental results and comprehensively considering the stability of the modification effect and the function requirements, Tween-20 (2.0% v/v) was chosen as the modifying reagents of the first siphon valve and the second siphon valve, and TritonX-100 (2.0% v/v) was chosen for the third siphon valve, which effectively reduces the contact angle and improves the liquid transfer efficiency, leading to further improvement of the rapidity and sensitivity of the centrifugal microfluidic immunoassay system by efficient siphoning and high plasma separation efficiency (99%).

A field programmable gate array based synchronization mechanism of analog and digital local oscillators in bandwidth-interleaved data acquisition systems.

This paper studies the synchronization between the analog and digital local oscillators (LOs) in bandwidth-interleaved (BI) data acquisition systems (DAQS). It gives a detailed analysis of the random synchronization phase difference between the analog and digital LOs in the BI-DAQS among different acquisition frames. Exploiting the synchrony relation between the analog LO and sampling clock of the BI-DAQS, the synchronization between analog and digital LOs, where the digital LO is generated in the sampling clock domain, in each acquisition frame is realized in the Field Programmable Gate Array (FPGA). A BI-DAQS platform with a 5.5 GHz bandwidth and 20 Gs/s sampling rate is built to validate the proposed synchronization mechanism. Experimental results in the platform show the efficacy of the proposed synchronization mechanism, which consumes only a small amount of the flip-flops and look-up tables in the FPGA without any additional hardware assistance.

A fast Fourier transform based method to estimate frequency response mismatches in time interleaved systems.

Time interleaving (TI) technique is widely used in acquisition systems to improve the sampling rate. However, as a parallel sampling structure, it inevitably brings in channel mismatches, such as the offset mismatch, gain mismatch, and time mismatch. Moreover, the gain mismatch and time mismatch are frequency-dependent, which means that the gain mismatch and time mismatch will be different when the signal frequency changes. This is because the gain and time mismatches are the special circumstances of frequency response mismatches. In this paper, a frequency response mismatch estimation method in TI acquisition systems is proposed and analyzed. First, the two kinds of mismatch models are compared to find the relationship between frequency response mismatches and the gain and time mismatches. Then, a mismatch estimation method that can estimate mismatches when the analog bandwidth exceeds the sampling rate of a single channel in a time interleaving analog to digital converter is proposed. Sinusoids with different frequencies are utilized to convert the question of estimating frequency response mismatches to acquiring the mismatch coefficients at a series of frequency points. Furthermore, a semi-automatic estimation technique is proposed to reduce the operation time, and a 10 GSPS eight-channel TI system is introduced. Simulations show the accuracy and effectiveness of the proposed method. At last, the frequency response mismatches are calibrated by using the estimated parameters. The calibration improves the performance of an eight-channel TI system from the original spurious free dynamic range of 27.6639 to 56.7029 dB and signal-to-noise ratio of 25.5468 to 32.7667 dB. The calibration result demonstrates the usefulness of the proposed method.

Frequency response mismatch calibration in 2-channel time-interleaved oscilloscopes.

The time-interleaved (TI) structure has been widely implemented in high speed, wideband data acquisition systems to increase the system sampling rate. However, the frequency responses of each sub-sampling path are not identical. This is named frequency response mismatches (FRMs). In TI-based printed circuit board level systems, due to the impact of the parasitic parameters, the FRMs are more complicated than the mismatches in TI analog-to-digital converters (TIADCs), which degrade the system performance severely. Therefore, the FRM calibration in 2-channel TI acquisition systems with two features is researched. The first one is that the TI system has a larger mismatch range than in most previous research. The second one is that the channel frequency response uses the general model. The calibration structure is established by the analysis of the digital TI model, which implements the TI operation in the digital domain to reconstruct the mismatches in the time domain. Furthermore, the problem of designing an arbitrary frequency response filter is transformed to the question of designing a three-stage cascaded filter group, which gives a method to realize the arbitrary frequency response in a real system. An oscilloscope prototype is proposed to verify the calibration performance. The simulation and experiment show the following: (i) Even though it uses the general frequency response and the FRMs are significant, the proposed method is still effective. (ii) The mismatch range of magnitude and phase responses is highly suppressed, and the spurious-free dynamic range is improved by 16.26 dB after calibration of the prototype.

Application of Microfluidics in Immunoassay: Recent Advancements.

In recent years, point-of-care testing has played an important role in immunoassay, biochemical analysis, and molecular diagnosis, especially in low-resource settings. Among various point-of-care-testing platforms, microfluidic chips have many outstanding advantages. Microfluidic chip applies the technology of miniaturizing conventional laboratory which enables the whole biochemical process including reagent loading, reaction, separation, and detection on the microchip. As a result, microfluidic platform has become a hotspot of research in the fields of food safety, health care, and environmental monitoring in the past few decades. Here, the state-of-the-art application of microfluidics in immunoassay in the past decade will be reviewed. According to different driving forces of fluid, microfluidic platform is divided into two parts: passive manipulation and active manipulation. In passive manipulation, we focus on the capillary-driven microfluidics, while in active manipulation, we introduce pressure microfluidics, centrifugal microfluidics, electric microfluidics, optofluidics, magnetic microfluidics, and digital microfluidics. Additionally, within the introduction of each platform, innovation of the methods used and their corresponding performance improvement will be discussed. Ultimately, the shortcomings of different platforms and approaches for improvement will be proposed.

A digital bandwidth interleaved structure correction method based on itemized correction.

To satisfy the input bandwidth and sampling rate requirements of data acquisition systems, digital bandwidth-interleaved analog-to-digital converters (DBI-ADCs) offer a practical parallel structure. However, the existing DBI-ADC correction methods are broadly inadequate in terms of design, testing, and implementation. Moreover, the evaluation and correction of the most significant feature of the DBI-ADC structure-wideband acquisition performance-is also imperfect. This paper proposes an itemized correction method for DBI-ADC structures. The proposed method simplifies the complex correction filter bank design algorithm into multiple simple correction filters and then separates and corrects the various errors of the DBI-ADC system. This dramatically simplifies the design, testing, and implementation process of the system, resulting in a highly convenient method for practical engineering. In addition, this method achieves a good correction effect, with an appropriate balance between the correction effect and the project implementation. Simulation results and experimental results verify the effectiveness of the proposed method.

An adaptive calibration technique of timing skew mismatch in time-interleaved analog-to-digital converters.

Because of the exponential increase of sampling rate, time-interleaved analog-to-digital converter (TIADC) has a fast growth in the high-speed applications. However, the channel mismatch error is a serious challenge for the performance of TIADC. In this article, we address the timing skew mismatch error and propose a novel adaptive calibration method. The principle and operating process of the calibration algorithm are explained. To validate the proposed technique, we designed a four-channel TIADC-based digital oscilloscope with a sampling rate of 10 GS/s. Based on this instrumentation platform, (i) calibration algorithm was implemented by hardware; and (ii) a test platform consisting of advanced instruments and tools was setup to testify the effect and robustness of proposed algorithm. Moreover, the technical details of instrumentation are described for the first time. The experimental results show that the calibration algorithm significantly suppresses the distortions due to timing skew mismatch error. The TIADC-based instrumentation achieves spurious-free dynamic range of 52.48 dB and effective number of bits of 5.83 bit, respectively. Besides, the complexity of the proposed algorithm is compared and discussed.

Real-time self-adaptive calibration method for high speed acquisition system.

The main factors that enable capture of complex and transient signals in real-time are improved sampling rates and processing speeds. The time-interleaved architecture is an effective method that allows systems to break through the speed bottleneck of single analog-to-digital converters (ADCs) and go beyond the state-of-the-art process technology limit. However, the performance of the acquisition system may be reduced because of the offset, gain, and time mismatch errors that occur in time-interleaved ADC systems. To correct these errors, this paper first proposes a self-adaptive correction algorithm and then introduces real-time solutions for this algorithm. Finally, the proposed calibration method is implemented in a digital phosphor oscilloscope. Simulations and experimental testing indicate that this system shows good real-time performance and provides a high dynamic performance with an effective number of bits of 7.3 bits and a signal-to-noise ratio of 45.5574 dB.

A seamless acquisition digital storage oscilloscope with three-dimensional waveform display.

In traditional digital storage oscilloscope (DSO), sampled data need to be processed after each acquisition. During data processing, the acquisition is stopped and oscilloscope is blind to the input signal. Thus, this duration is called dead time. With the rapid development of modern electronic systems, the effect of infrequent events becomes significant. To capture these occasional events in shorter time, dead time in traditional DSO that causes the loss of measured signal needs to be reduced or even eliminated. In this paper, a seamless acquisition oscilloscope without dead time is proposed. In this oscilloscope, three-dimensional waveform mapping (TWM) technique, which converts sampled data to displayed waveform, is proposed. With this technique, not only the process speed is improved, but also the probability information of waveform is displayed with different brightness. Thus, a three-dimensional waveform is shown to the user. To reduce processing time further, parallel TWM which processes several sampled points simultaneously, and dual-port random access memory based pipelining technique which can process one sampling point in one clock period are proposed. Furthermore, two DDR3 (Double-Data-Rate Three Synchronous Dynamic Random Access Memory) are used for storing sampled data alternately, thus the acquisition can continue during data processing. Therefore, the dead time of DSO is eliminated. In addition, a double-pulse test method is adopted to test the waveform capturing rate (WCR) of the oscilloscope and a combined pulse test method is employed to evaluate the oscilloscope's capture ability comprehensively. The experiment results show that the WCR of the designed oscilloscope is 6,250,000 wfms/s (waveforms per second), the highest value in all existing oscilloscopes. The testing results also prove that there is no dead time in our oscilloscope, thus realizing the seamless acquisition.