A novel strategy for in situ maskless synthesis of biochips:Self-driving micro-fluid porous type printing (SMPTP)

A novel maskless technique, self-driving micro-fluid porous type printing （SMPTP）, was reported to in situ synthesize oligonucleotide arrays on glass slide, which has the merits of low cost, high quality and simple craft. In SMPTP for fabricating gene- chips, porous fiber tubes with a number of nanometric or micron channels functioned as ＂active letters＂ and were assembled in designed patterns, which are identical to the distribution of monomers in each layer of the array, and four patterns were needed for each layer. By means of capillarity, the synthesis solution was automatically taken into porous tubes assembled in a printing plate and reached the surface. An oligonucleotide array of 160 features with four different 15-mer probes was in situ synthesized using this technique. The four specific oligonucleotide probes, including the matched and the mismatched by the fluorescent target sequence, gave obviously different hybridization fluorescent signals.

Combination of Micro-fluidic Chip with Fluorescence Correlation Spectroscopy for Single Molecule Detection

A single molecule detection technique was developed by the combination of a single channel poly （dimethylsiloxane）/glass micro-fluidic chip and fluorescence correlation spectroscopy （FCS）. This method was successfully used to determine the proportion of two model components in the mixture containing fluorescein and the rhodamine-green succinimidyl ester.

Research of Confocal Laser Induced Fluorescence Detection System for Micro-fluidic Chip

The characteristics such as signal noise ratio（SNR） and sensitivity of the fluorescence detection system for micro-fluidic chip influence the performance of the whole system extremely. The confocal laser induced fluorescence detection system is presented. Based on the debugging of optical and circuit modules, the results of detecting the samples are given and analyzed theoretically, and the improved project is put forward.

Evaluation of specific fecal protein biochips for the diagnosis of colorectal cancer

AIM: To develop and initially test a potential fecal protein biochip for the screening of colorectal cancer (CRC).

Biosensors and Biochips Based on BioMEMS and Nanotechnology

In the past two decades,the biological and medical fields have seen great advances in the development of biosensors and bioehips capable of characterizing and quantifying biomolecules.This lecture is meant to discuss the development and applications of advanced electroanalysis,biophotonics,nanotechnology,MEMS- based biosensors and biochips for biomedical diagnostics and physical performances of athlete.

A NOVEL TECHNIQUE FOR MULTIPLE FAULTS AND THEIR LOCATIONS DETECTION AND START ELECTRODE SELECTION IN MICROFLUIDIC DIGITAL BIOCHIP

A device,that is used for biomedical operation or safety-critical applications like point-of-care health asssment,massive parallel DNA analysis,automated drug discovery,air-quality monitoring and food-safety testing,must have the attributes like relia bility,dependability and correctness.As the biochips are used for these purposes;therefore,these devices must be fault free all the time.Naturally before usi ng these chips,they must be well tested.We are proposing a novel technique that can detect mutiple fults,locate the fault positions within the biochip,as well as calculate the traversal time if the biochip is fault free.The proposed technique also highlights a new idea how to select the appropriate base node or pseudo source(start electrode).The main idea of the proposed technique is to form multiple loops with the neighboring electrode arrays and then test each loop by traversing test droplet to check whether there is any fault.If a fault is detected then the propoed technique also locates it by backtracking the test droplet.In case,no fault is detected,the biochip is fault free then the proposed technique also calculates the time to traverse the chip.The result suggests that the proposed technique is eficient and shows significant improvement to ca lculate fault-free biochip traversal time over existing method.

A deep-reinforcement learning approach for optimizing homogeneous droplet routing in digital microfluidic biochips

Over the past two decades,digital microfluidic biochips have been in much demand for safety-critical and biomedical applications and increasingly important in point-of-care analysis,drug discovery,and immunoassays,among other areas.However,for complex bioassays,finding routes for the transportation of droplets in an electrowetting-on-dielectric digital biochip while maintaining their discreteness is a challenging task.In this study,we propose a deep reinforcement learning-based droplet routing technique for digital microfluidic biochips.The technique is implemented on a distributed architecture to optimize the possible paths for predefined source–target pairs of droplets.The actors of the technique calculate the possible routes of the source–target pairs and store the experience in a replay buffer,and the learner fetches the experiences and updates the routing paths.The proposed algorithm was applied to benchmark suitesⅠand Ⅲ as two different test benches,and it achieved significant improvements over state-of-the-art techniques.

Preface for advances in biochips

Biochip is essentially a bio-microarray device that can perform hundreds or thousands of simultaneous biochemical reactions.[1, 2] It offers the researchers a new way for large-scale genomic, proteomic and functional genomic analyses. The biochips also enable people to quickly screen large numbers of biological analyses for many different purposes, from disease diagnosis to detection of bioterrorism chemical agents.[3]

Investigation into the hydrodynamics of liquid-solid inclined micro-fluidized beds

The inclined micro-fluidized bed(MFB)can enhance heat and mass transfer rates compared to the vertically aligned counterparts,but the increased significance of surface forces and wall effects may cause poor fluidization performance.In this paper,the effects of column inclination and different particle-to-bed ratios(d_(P)/d_(B))on the solid hydrodynamics are investigated in an inclined micro-fluidized bed.The results validated the suitability of using the Ergun equation to predict minimum fluidization velocities due to small deviations between 1.01 and 1.81 times the theoretical values,for a particle-to-bed ratio ranging from 0.025 to 0.165 at inclinations between 0°and 10°.Investigation into the effects on bed expansion behavior showed that the bed contracted with an increase in bed inclination.An unexpected observation during the bed expansion was the appearance of a secondary high voidage region and the appearance of strong circulation patterns with an increase in bed inclination.A detailed analysis of this phenomenon suggested the presence of a critical angle at 6°and 10°for the 85μm particles,4×4 mm bed cross-section and 165μm particles,1×1 mm bed cross-section,respectively.However,the liquid-solid back-mixing was observed due to the modified particle trajectories resulted in the disappearance of the high voidage region.This paper gives new insights into the micro-fluidization behavior in inclined beds thus contributing to the development of micro-fluidized beds and their future applications.

基于B^(*)-树的连续微流控生物芯片流层物理设计方法

作为连续微流控生物芯片设计中的关键步骤,流层物理设计是一个复杂的多目标优化问题,传统方法通常将其分为布局和布线2个阶段。为弥补这2个阶段之间的交互不足,提出了一种基于B^(*)-树的流层物理设计方法,以提高解的质量和求解效率。在布局阶段,采用Memetic算法更高效地搜索解空间。在布线阶段,使用考虑通道顺序的基于协商的算法,同时将布线信息反馈给布局阶段,以调整布局并减少拥挤区域和通道交叉。实验结果表明,与现有算法相比,所提算法在芯片面积、通道总长度以及通道交叉数量等方面取得了更优的效果。

基于混合离散粒子群优化的控制模式分配算法

连续微流控生物芯片是生物化学实验自动化、微型化的革命性技术.多路复用器的控制模式分配作为连续微流控生物芯片自动化设计的关键环节之一,是难的NP(Non-deterministic Polynomial)优化问题.现有工作采用粒子群优化算法求解控制模式分配问题存在过早陷入局部最优解、收敛速度慢以及算法稳定性差的缺点.为此,本文提出一种连续微流控生物芯片下基于混合离散粒子群优化的控制模式分配算法.首先,为了加快算法收敛速度及避免过早陷入局部最优解,提出了离散的自适应区域搜索策略.其次,通过基于样例的社会学习机制提高了算法的稳定性.然后,采用等距抽值的方式筛选出自适应区域搜索策略中重要参数的最佳组合,以进一步提高分配方案的质量.最终实验结果表明,所提算法在多路复用器中阀门使用数量上平均优化了19.01%,在算法稳定性上提高了29.18%,且在现实的生化应用中有良好的性能表现.

面向数字微流控生物芯片的差分隐私方案

近年来,基于数字微流控生物芯片(Digital Microfluidic Biochip,DMFB)的分子诊断技术成为热点研究方向。与传统分子诊断技术相比,数字微流控生物芯片具有精准控制离散液滴、执行生化协议等优势。然而,作为网络物理系统的组成,生物芯片潜在的隐私安全问题日益突出,比如通信信道的窃听攻击,生化协议的篡改攻击,物理结构保护的版权攻击等。差分隐私作为传统数据隐私保护的常用技术可以融入生物芯片应用以保护用户隐私安全。然而,对隐私安全、生物芯片应用以及生物芯片安全三种技术的交叉研究较为少见。调研分析生物芯片应用的实现机制和威胁模型,包括生化协议、网络物理系统及增强隐私保护的DMFB用户数据安全平台,首先在DMFB用户数据平台上描述了拉普拉斯机制、高斯机制和随机响应机制的应用场景和保护方案,其次基于用户层级敏感度、路由权重集合和路由交叉点参数集合这三个策略提出参数安全发布算法,最后创建防篡改概率作为安全性指标,同时建立置信分数、校准度和累计误差率衡量数据可用性。仿真实验结果表明整体方案的隐私安全性可达98%,数据可用性平均可达93.3%,算法性能试验表明方案最佳的隐私预算为0.4,此外,对比同类算法,所提方案平均提高了12.09%隐私安全性和7.02%的数据可用性,因此该方案能够为DMFB执行生化协议安全有效的用户数据平台。

生物芯片技术在食品检验中的应用研究

随着食品安全问题日益受到关注,生物芯片技术作为一种高效、高通量的检测方法,在食品检验中展现出广阔的应用前景。本文综述了生物芯片技术的原理及其在食品检验中的应用,并探讨了其面临的挑战与未来发展前景。

致病性弧菌检测新技术研究进展

随着人们对水产品需求的增加及致病性弧菌引发的食源性疾病的流行,致病性弧菌对水产养殖业及人类健康造成了巨大威胁,基于此,致病性弧菌检测新技术的开发变得尤为迫切。本文介绍了包括免疫学方法、核酸检测方法、基于生物芯片的检测方法、基于核酸适配体的检测方法、基于肽质量指纹图谱技术的检测方法、基于生物传感器技术的检测方法在内的6项检测技术,分析了其优缺点及其在致病性弧菌中的应用。最后,总结了致病性弧菌检测新技术的研究现状,结合新兴技术指出未来研究方向,为致病性弧菌的快速检测提供参考。

完全可编程阀门阵列生物芯片下容错导向的高阶综合算法

作为新一代流式微流控生物芯片,完全可编程阀门阵列(FPVA)生物芯片具有更高的灵活性和可编程性,已经成为一种流行的生物化学实验平台。然而,由于环境或人为因素,制造过程中通常存在一些物理故障,如通道阻塞和泄漏,这无疑会影响生化检测的结果。此外,高阶综合作为架构综合的首要阶段,其结果的质量直接影响着后续设计的优劣。因此,该文首次研究了FPVA生物芯片高阶综合过程中的容错问题,提出了单元功能转换方法、双向冗余方法、故障映射方法等动态容错技术,为实现高效的容错设计提供了技术保障。通过将这些技术集成到高阶综合设计中,进一步实现了一种高质量的FPVA生物芯片下容错导向的高阶综合算法,包括故障感知的实时绑定策略和故障感知的优先级调度策略,为实现芯片架构的鲁棒性和检测结果的准确性奠定了良好的基础。实验结果显示,所提算法能够得到一个FPVA生物芯片下高质量且容错的高阶综合方案,为后续实现容错物理设计方案提供了有力保障。

基于生物芯片技术的生乳中兽药检测方法验证及其应用

为验证生物芯片技术在生乳兽药检测方面的效果并进行推广应用,针对80种常见兽药,采用生物芯片快速检测法对生乳样品进行检测,并同时采用高效液相色谱-串联质谱(high performance liquid chromatographytandem mass spectrometry,HPLC-MS/MS)法确认。结果表明:生物芯片法检出限符合国家标准检出限要求,且部分优于国家标准;该方法线性范围较宽,相关系数均>0.99,线性范围内呈良好的相关性;通过阴性样品加标回收实验,对加入2倍与4倍检出限的标准样品进行测定,加标回收率为70%~130%,变异系数为5%~10%;该方法前处理简单、检测周期短、灵敏度高、通量大,适合大批量样品的快速筛查。利用以上方法对2022—2023年采自上海辖区内的100批次生乳进行检测发现,含有兽药残留的生乳共10批,其中链霉素检出4批(检出值5.86~10.26μg/kg),磺胺吡啶检出3批(检出值1.09~1.42μg/kg),磺胺间二甲氧嘧啶检出2批(检出值1.38~1.46μg/kg),阿维菌素检出1批(检出值1.75μg/kg),经过国标方法确证,以上检出值均远低于国际组织、农业农村部公告或国家标准限量规定。生物芯片法相较于传统的HPLC-MS/MS法具有灵敏度高、线性范围宽和检测速度快等优势,可作为生乳兽药残留快速检测的补充手段,具有较高的应用价值。

动物源性食品中5类兽药残留的生物芯片试剂盒检测准确性评估

该研究基于微阵列生物芯片试剂盒法评估了动物源性食品中多种兽药残留检测的结果准确性。使用微阵列生物芯片试剂盒法分别对鸡肉、鱼肉、猪肉、乳制品、蜂蜜5种动物源性食品基质中的喹诺酮类、四环素类、氟苯尼考、磺胺类和甲氧苄啶残留量进行测定,考察生物芯片试剂盒法的检出限和定量限,对结果进行准确性评估。结果显示,该方法对5种食品基质中5类兽药残留的检出限和定量限均满足要求,选用鱼肉、蜂蜜和乳制品3种基质加标进行检测,5类兽药残留的加标回收率结果均在72.58%~119.87%之间,RSD均在0.21%~22.49%内,与确证方法进行比较,未出现假阳性或假阴性结果,准确性较好。结果表明,生物芯片试剂盒法检测速度快、成本低、结果准确可靠,在动物源性食品多兽药残留同时筛检中具有广阔应用前景。

不同工艺参数对生物微流控芯片结构合成的影响

本文研究了纳米压印光刻技术在微流控生物芯片制造中替代传统光学光刻技术的可行性。首先探究了V50,V60和V703种不同压印胶胶型及不同转速对压印生物芯片结构的影响,最终选择了浓度较高的V70压印胶在转速为3000 r:·min^(-1)条件下进行旋涂。在电感耦合等离子体刻蚀(inductively coupled plasma,ICP)工艺参数方面,保持其他变量不变,研究了不同刻蚀时间对制备生物芯片结构的影响,最终选择刻蚀时间为900 s。研究结果表明上述条件下所制备的生物芯片微结构具备透光性良好、残余层薄和转移精度高的优点。该方法的工艺简单,具有良好的操作性和可重复性,为生物微流控芯片的制备提供了一种有效且高效的解决方案。同时优化了纳米压印和ICP刻蚀的工艺参数。实现了制备微流控生物芯片时所需的纳米压印设备和刻蚀设备所需的关键参数,为未来微流控芯片的开发和优化提供了实验数据和参考依据。

p16INK4a联合人乳头瘤病毒及液基细胞学检查在宫颈上皮内瘤变临床诊断中的应用

目的分析p16INK4a蛋白、人乳头瘤病毒及液基细胞学检查(LCT)在宫颈癌前病变筛查中的检测效率,为宫颈癌的预防和治疗提供依据。方法分析2019年1月—2020年6月广州市妇女儿童医疗中心的139例住院患者的宫颈上皮细胞p16INK4a染色、人乳头瘤病毒检测及宫颈细胞学检测结果。这些病例包括111例宫颈上皮内瘤变(CIN)患者和28例宫颈炎性疾病患者。比较三种方法单独及联合应用筛查CIN病变的效能。结果在对CIN患者的检测中,p16INK4a、生物微流控芯片和宫颈细胞学检测CIN及以上病变的灵敏度分别为91.89%、94.59%和78.20%,特异度分别为57.14%、17.86%和46.43%,AUC分别为0.75、0.56和0.66。而“p16INK4a+LCT”、“p16INK4a+hrHPV”、“LCT+hrHPV”以及三种方法联合检测的灵敏度分别为96.40%、97.30%、94.59%和99.10%,特异度分别为85.71%、92.86%、89.29%和92.86%,AUC分别为0.91、0.95、0.92和0.96。结论p16INK4a和hrHPV联合检测有助于提高诊断的准确性和早期发现率,从而使得能更早进行干预或治疗。通过这种联合应用,可以更准确地鉴别出低级别和高级别的宫颈上皮内瘤变,为个性化的病患管理提供更多信息。

基于STM32F4+OV2640的HPV生物芯片阅读装置设计

定期开展HPV分型筛查,对提高妇女健康水平、预防宫颈癌发生的意义重大。为提高检测的自动化水平,减少人工介入和人为误判,设计HPV生物芯片阅读装置的重要性显著。采用STM32F429处理器结合OV2640CMOS传感器,配备M12镜头和可移动30 mm的载物台,可充分发挥可见光显色的TIB-23型HPV生物芯片的筛查优势。结果表明,所设计的HPV生物芯片阅读装置可直接使用HPV芯片杂交仪生化反应托盘,成功阅读四联装TIB-23型HPV生物芯片。该装置对提高HPV分型筛查自动化水平具有重要意义。