Congratulations! TingTing and Yaoping’s work about highly efficient and controllable cell alignment was published on Microsystems & Nanoengineering!

In this study, a novel solid lift-off method using an ingeniously designed micropore array as a shadow mask was proposed. Efficient and precise control of cell alignment and spreading simultaneously was realized via an ingenious composite-confining structure design, with large micropores (capture pores) in central areas and small micropores (spreading pores) in surrounding areas dominating capture/alignment and adhesion/spreading, respectively.

High-throughput (2.4−3.2×104/cm2) cell patterning were achieved with high efficiencies (86.2 ± 3.2%, 56.7 ± 9.4% and 51.1 ± 4.0% for single-cell, double-cell, and triple-cell, respectively). Precise control of spreading and application toward regulating cell skeleton and cell-cell junction distribution was investigated and verified using murine skeletal muscle myoblasts. To our knowledge, this is the first report to demonstrate highly efficient and controllable multi-cell alignment and adhesion/spreading simultaneously via a simple single-step solid lift-off operation. Notably, this study successfully fills a gap in the literature and promotes the effective and reproducible application of cell patterning methodologies. This work will attract extensive interests in the fields of both basic cellular mechanism research and applied medicine including organ-on-a-chip, tissue engineering, etc.

Full text can be found: https://www.nature.com/articles/s41378-020-00191-5

Tingting Hun#, Yaoping Liu#, Yechang Guo, Yan Sun*, Yubo Fan* and Wei Wang*, A micropore array-based solid lift-off method for highly efficient and controllable cell alignment and spreading. microsystems & nanoengineering 6, 86 (2020)

Doi: https://doi.org/10.1038/s41378-020-00191-5

Congratulations! Tingyu and Yaoping’s work about liquid biopsy of lung cancer was published on Theranostics!

This work realizes a rapid liquid biopsy of lung cancer by separation and detection of exfoliated tumor cells from bronchoalveolar lavage fluid (BALF) with a dual-layer PERFECT (precise, efficient, rapid, flexible, easy-to-operate, controllable and thin) filter system. A preliminary clinical trial enrolling 33 patients has been performed to verify the efficacy of the developed system.

The novel system possesses the following breakthroughs and advantages.

  • This system enables a short time-to-result (<30 min), benefiting from the handling ability of large-volume clinical BALF samples (6-18 mL) of complex contents at a high filtration throughput (54.6% BALF specimens were filtrated within 3 min, and others could be finished completely within 10 min).
  • A high detection sensitivity (80.0%) has been demonstrated, significantly higher than that from the conventional cytocentrifuge (45%). The sensitivity of this platform is neither interfered by the variations of turbidity of the BALF samples, nor associated with the types of lung cancer.
  • This system is compatible with various downstream analysis platforms such as immunofluorescence/immunocytochemistry staining, FISH test, PCR, sequencing and even the AI-based automatic diagnosis, which will fulfill both clinical practices and advanced mechanism studies.
  • The handiness in system set-up, ease of operation, wide adaptability and readiness for integration with related systems, will facilitate the developed system to find powerful applications in clinical practices, such as efficient separation and detection of rare tumor cells, fungi and bacteria from blood, urine, sputum etc.

Full text can be found: https://www.thno.org/v10p6517.htm

Tingyu Li#, Yaoping Liu#, Wei Zhang, Jixin Zhang, Yan Xiong, Ligong Nie, Haichao Li* and Wei Wang*, A rapid liquid biopsy of lung cancer by separation and detection of exfoliated tumor cells from bronchoalveolar lavage fluid with a dual-layer “PERFECT” filter system, Theranostics, 2020; 10(14): 6517-6529.

Doi: 10.7150/thno.4427410 (14): 1591-1606.

北京大学微米/纳米加工技术国家重点实验室王玮教授课题组招收3-4名科研实习生

【主要方向和工作内容】

传统上,对各种疾病的诊断仍以侵入式组织活检为主,这不仅会影响患者的体验和临床效应,还会导致早期发现和监控等领域的新方法难以实施。液体活检作为一种新的取样和检测手段,其非侵入特性将会取代传统的基于组织的诊断。这种手段也已被逐渐应用在越来越多的临床背景中,对各类疾病的发现和控制手段起到了重塑作用。

目前王玮教授课题组针对临床诊断、生物医学基础研究等对大体积(≥10 mL)、复杂背景环境下痕量生物对象捕获的迫切需求,成功开发出柔性微/纳孔滤膜,面积可达20 mm×20 mm,厚度仅为10 μm,孔隙率最高可达91%,形成了超高体积通量(仅靠重力驱动,未稀释全血样品操作能力≥17 mL/min,国际报道最优指标的8倍),超高检测灵敏度(10 mL样品中低至单个目标细胞检出)的液态活检新方法,实现了全血中循环肿瘤细胞/细胞团检出、肺泡灌洗液/痰液/胸水等肺癌相关液态活检标本中脱落肿瘤细胞/细胞团检出,其中基于肺泡灌洗液肿瘤细胞学的肺癌诊断敏感性从45%提升至80%。基于该技术,课题组已与北京大学第一医院、北京大学人民医院、北京协和医院、佑安医院、安徽省胸科医院、大连医科大学附属第二医院等多家医院的覆盖检验科、呼吸内科、泌尿外科、皮肤科、重症监护室、肝脏研究中心等多个临床科室合作,开展所开发的液态活检技术在多种恶性肿瘤、微生物(包含病毒)临床诊断中的应用;此外,课题组所开发的柔性微孔滤膜还被美国麻省理工学院、加州大学戴维斯分校、波士顿大学、圣母大学、瑞典皇家理工学院、新加坡国立大学以及清华大学、上海交通大学、复旦大学和德国默克(Merck)、韩国MD Immune、北京莱尔生物有限公司、北京科途医学科技有限公司、苏州创澜生物科技有限公司等多家单位知名大学研究团队与公司应用于多种细胞/微生物分离的研究和应用中,受到广泛好评,展现出优异的应用潜力。研究成果获第46届日内瓦国际发明展特别嘉许金奖(2018年)、第13届北京发明创新大赛银(2019年)、大连市科学技术一等奖(2019年)、先进体外诊断行业峰会“最佳创新能力奖”(2018年)、第5届微米纳米技术创新与产业化科研成果转化学生大赛一等奖(2018年)、北大医院首届转化医学大赛一等奖(2018年)等奖励。更多详细信息请参见小组网站http://byu8102860001.my3w.com/

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图1 课题组开发的柔性微/纳孔滤膜技术已在多家医院、研究机构和医疗诊断企业得到应用。

为推进相关研究工作的临床应用,现招收对该研究方向感兴趣的科研实习者。主要研究方向如下:

  1. 基于柔性微孔滤膜的细胞力学性能分析与筛选:包括血液中稀有循环肿瘤细胞的俘获,及力学性能筛选、肿瘤干性分析、药效评估等肿瘤相关重要基础机制研究及临床应用效能验证。
  2. 基于柔性微孔滤膜的肺泡灌洗液肿瘤液态活检标准化方法(获Merck创新基金资助):包括临床肺泡灌洗液样品的消化、稀释等过滤前处理方法优化、过滤过程多物理场耦合调制、过滤后滤膜上所俘获肿瘤细胞的下游生化分析(如测序)等,最终实现肺泡灌洗液肺癌液态活检标准化技术方案及临床应用效能验证。
  3. 基于柔性微孔滤膜的自体血回输:包括全血中特定目标对象(如白细胞、红细胞、血浆等)的高效非离心式分离,多形态、多尺寸、多变形能力分离对象的参数化过滤模型,多外力场(振动、侧向流等)辅助的主动过滤调制,实现非离心式自体血回输关键技术及临床应用效能验证。

【科研训练/工作模式】

  1. 刚开始由王玮教授和组内负责该研究方向的师兄/师姐带着熟悉相关工作内容,熟悉、上手后很快自己独立承担其中某个分支工作,由王玮教授直接指导。
  2. 支持发表领域内相关会议、期刊论文并在论文接收的情况下支持前往参加学术会议/论坛/研讨会。小组历届的本科科研实习者基本都有至少1篇次文章/会议经历(人数比例>85%),大于2篇次者人数比例>50%。

【基本要求】

  1. 不限年级,包括gapper;
  2. 绩点>3.5(绩点不是衡量科研水平和决定面试结果的硬性指标,具体可在面试时协谈;历届本研实习者中曾有多人次以<3.0绩点、基于出色的科研成果,在出国读博申请中拿到top offer);
  3. 有细胞生物学、分子生物学、流体计算/仿真、图像处理、人工智能、机器学习等任何一方面基础者优先考虑。

【报名及面试方式】

  1. 有意者请发送简历至w.wang@pku.edu.cn,邮件注明主题:科研实习+姓名;简历包括个人基本信息、教育经历、科研经历(如有)、已学专业课程等相关资料;
  2. 初试通过者将安排面试,根据面试成绩择优录取。

【团队优势】

  1. 课题组拥有浓厚的科研氛围和丰富多彩的日常活动、温馨的团队文化;
  2. 课题组具有深入的交叉学科研究及合作基础,团队成员包括微电子、物理学、生物学、医学、生物医学工程、精密仪器等专业的博士后、研究生、本科生及近10年深度合作的临床医生;
  3. 本团队与世界一流大学的众多教授、领域领先企业与国内多家三甲医院具有广泛深入的合作关系;
  4. 课题组历届本科科研实习生在“飞跃重洋”申请中获得Harvard、MIT、CalTech、UC Berkerley、Princeton、Rockefeller等top院校offer;
  5. 一定数目的助研补助,科研投入越多,补助越多;发表学院A类论文后再单独发放奖励金;表现优异/并有意向者可保研或直博,也可以推荐到国外相关院所进行交流研究等。

无论你的兴趣在临床应用转化还是基础理论研究(倾向于实验操作or倾向于数值模拟计算均可),都可以在这个大团队中找到施展空间,都会得到来自王玮老师以及师兄/师姐尽可能多的支持来满足你的研究兴趣。

【背景介绍】

液态活检微纳米技术因在疾病(如癌症)早期诊断/治疗过程动态监测、疗效评估的重要作用而备受关注和推崇。液体活检技术是MIT科技综述(MIT Technology Review)杂志公布的2015年度十大突破技术之一;福布斯杂事评定为未来五大医疗行业颠覆技术;摩根大通预测:全球千亿美元市场价值。液体活检属于精准医疗计划的重要部分,2015年1月底美国总统奥巴马宣布一个生命科学领域新项目-精准医疗计划,该计划致力于治愈癌症和糖尿病等疾病。2015年3月中国卫计委和科技部也先后召开国家首次精准医疗战略专家会议,提出在2030年前投入600亿人民币用于精准医疗,精准医疗被列入十三五重大科技专项。

微米/纳米加工技术国家重点实验室(北京大学)王玮教授课题组博士后招聘

博士后招聘方向:

  1. 先进液态活检技术及其在临床诊断中的应用,包括:(1)自体细胞分析与功能化研究平台;(2)肿瘤、微生物(如真菌等)的快速精准诊断与鉴别技术。
  2. 三维集成与热管理方向,包括:(1)热管理方向:微流道散热仿真设计、热点仿真、微流道散热芯片加工与测试、大功率集成微系统的热管理;(2)先进封装方向:类脑芯片等先进计算芯片、小芯片的三维集成架构设计,异质异构芯片的混合集成。

申请条件:

  1. 液态活检方向:专业背景为微电子、电子工程、生物学、医学或与以上研究方向相关专业等,具有临床医学研究经验者优先;三维集成与热管理方向:专业背景为微电子、电子工程、热物理学、计算机程序设计或与以上研究方向相关专业等,具有先进封装工艺研究经验者优先;
  2. 已获得博士学位(原则上不超过三年),或即将获得博士学位,品学兼优,身体健康,年龄不超过35周岁;
  3. 以第一作者身份在相关领域发表过SCI论文;
  4. 具有良好的基本实验技能和英文阅读、写作、口头表达能力,能独立负责课题方向完成研究工作;
  5. 踏实肯干,有科研热情及一定的团队协作能力;
  6. 符合北京大学有关博士后管理规定。相关规定网页:https://postdocs.pku.edu.cn/

待遇:

  1. 按照国家和北京大学博士后管理规定享受职工相关工作和生活待遇(五险一金,子女入学入托及博士后公寓(视学校房源而定)或租房补贴),包括相关医疗、工会入会、体检等福利待遇;
  2. 协助申请北大博雅博士后、国家博新博士后等;
  3. 薪酬:全职博士后基本年薪12万以上,在此基础之上,依据实际水平和在站工作表现,课题组发放津贴与年终奖励;
  4. 提供基本研究条件、研究经费和科研设备;
  5. 在站期间课题组将协助博士后人员申请各类基金项目,如国家自然科学基金、中国博士后科学基金等。

申请方式:

将申请函(包括个人简历及两封推荐信等相关证明材料,简历包括学习工作经历、主要研究工作内容、代表论文论著、获得的奖励情况等)发送至合作导师邮箱:王玮,w.wang@pku.edu.cn。邮件标题注明:“应聘博士后+姓名+毕业学校”。初选通过后,邮件通知候选人进行面试。

合作导师简介:

王玮,北京大学教授。2005 年于清华大学航天航空学院获博士学位(导师过增元院士),之后加入北京大学信息科学技术学院和微米/纳米加工技术国家重点实验室,现任重点实验室常务副主任、北京大学微纳电子学系副系主任、北京大学集成微纳系统(MEMS)研究所所长。主要从事生物微机电系统(bioMEMS)、聚合物微纳加工方法、临床诊疗微纳系统相关研究,发表 SCI 检索期刊论文50余篇,领域顶级国际会议论文50余篇,授权、申请发明专利及软件著作权20余项。担任微机电系统领域顶级国际会议 IEEE MEMS’2015、’2016、Transducers’2019 的执行技术委员会委员,微纳流体前沿国际会议’2015 共同主席;担任多个应用中心、重点实验室学术委员会主任或委员。

更多信息请看课题组网站: http://byu8102860001.my3w.com/

团队优势:

  1. 液态活检方向:本团队拥有国际领先的柔性微孔滤膜技术,发表多篇高水平研究论文、申请多项发明专利、在多项发明展及比赛中获奖,并在全球范围内超过50家研究院所、医院和公司得到广泛应用;与MIT、新加坡国立大学等世界一流大学的众多教授,京东方、莱尔等领域领先企业以及北京大学第一医院、大连医科大学附属第二医院等国内多家三甲医院具有广泛深入的合作关系。
  2. 热管理与三维集成方向:本团队与世界一流大学的众多教授、领域领先企业具有广泛深入的合作关系,对于在本组工作优秀者可推荐去世界一流大学学习或华为、航天、中电等领域领先企业工作。
  3. 课题组拥有浓厚的科研氛围和温馨的团队文化;
  4. 课题组具有深入的交叉学科研究及合作基础,现有团队成员包括微电子、物理学、生物学、医学、生物医学工程、精密仪器等专业研究生、本科生。
  5. 依托平台微米/纳米加工技术国家重点实验室设备近亿元,拥有功能齐全的微米/纳米加工平台。

Congratulations! TingTing and Yaoping’s work on in-situ electroporation was reported in IEEE MEMS’ 2020 conference!

Labelling-assisted visualization is a powerful strategy to monitor the track of targeted cells for mechanism study, such as tumor metastasis. This work proposes an in-situ electroporation on an ultra-thin and high-porosity micropore-arrayed filter to introduce a fluorescent dye label into targeted cells. Continue reading “Congratulations! TingTing and Yaoping’s work on in-situ electroporation was reported in IEEE MEMS’ 2020 conference!”

Congratulations! 5 works from Cell Subgroup were reported in Microtas’ 2019 conference!

1. Tingyu and Yaoping’s work about PVA-Functionalized filter for efficient cell recovery and release

This work reports a Polyvinyl Alcohol (PVA)-functionalized filter based on an easy spin-coating process for effective cell capture and release. The PVA-functionalized filter (10-μm-diagonal-micorpore) realized a high recovery rate (82.7±6.4%) of cell separation from a large-volume liquid sample (105 A549 cells spiked in 5 mL PBS) by a gravity-driven filtration in a few seconds. And an easily-operated and rapid (soaking in PBS for 3 minutes) cell release was realized at a high release rate (96.2±8.5%), along with a high cell viability (92.7±0.7% verified via the trypan blue staining), which is critical for further downstream analysis. These results demonstrate the proposed PVA-functionalized filter will find promising applicability in target cell separation for liquid biopsy.

 

2. Yaoping and Meixuan’s work about Kirigami-inspired mesh for rare cell recovery

This work proposes a Kirigami-inspired mesh to achieve an effective recovery of rare cell from whole blood. The shape and size of the micropores were well programmed via careful design of the geometric size of the Kirigami structure and accurate control of the strain loading of stretch. Two different shaped (diamond and hexagon) micropore arrays were successfully realized through the stretching operation. The applicability in rare tumor target retrieval was verified and the recovery rate of rare spiked cancer cell from undiluted whole blood reachedupto81.2±15.2%(67%strainfordiamond-shapedmicropore) at a high throughput (>18mL/(min∙cm2)).

 

3. Tingting and Yaoping’s work about a circulating filtration system for cell recovery

Filtration has been widely known as a promising approach to effectively achieve rare target cell recovery from large-volume samples at a high throughput for liquid biopsy. This paper proposes a circulating filtration system to achieve the recovery of rare target cells at a high efficiency along with a high purity.

4. Wenbo and Yaoping’s work about rapid separation and detection of rare fungi spores from whole blood based on a dual-layer micropore array filtration

This work reports a novel dual-layer filtration system including two membranes with different micropore diameters for rapid separation of fungi spores from undiluted whole blood. The upper membrane is for the depletion of white blood cells (WBCs) and the lower filtration membrane is for the recovery of targeted spores while depleting red blood cells (RBCs). The results demonstrated a rapid spore separation with high recovery rates (82.47%±10.90% from undiluted whole blood with rare spiked spores as targets), along with low blood cell contamination. The proposed system will be a promising point-of-care detection (POCD) tool for fungemia.

5. Yaoping’s work about large-scale nanopore array based on a cost-effective shrinkage process for nanosized target separation

This work proposes a cost-effective shrinkage-based process for large-scale Parylene-C nanopore array fabrication from a prepared micropore array. The diameter of nanopore was well controlled via tuning the shrinkage thickness.  Large-scale (>1 cm2) and uniformly-distributed nanopore arrays with different diameters (100‒900 nm) and only a small thickness (<8 μm) are successfully achieved. The prepared nanopore array was packaged with a home-designed gadget for nanoparticle recovery (104 in 1 mL PBS) through a filtration driven by a centrifugation (200 rpm@1 min). A good performance in nanoparticle recovery is well demonstrated, which indicates the promising applicability in exosome separation for liquid biopsy.

 

微纳电子学系王玮教授课题组在超大体积通量液态活检领域取得系列重要进展

  北京大学微纳电子学系王玮教授课题组基于聚对二甲苯微机电系统(Parylene C MEMS)工艺开发了一种具有高孔隙率(最高可达91.37%)、大面积(大于20 mm×20 mm)的2.5维柔性微孔滤膜。   Continue reading “微纳电子学系王玮教授课题组在超大体积通量液态活检领域取得系列重要进展”

Featured in a recent issue of Lab on a Chip

Congratulations! Yaoping’s work “A high-throughput liquid biopsy platform based on a 2.5D micropore-arrayed filtration membrane” is featured in a recent issue of Lab on a Chip! This technique will enable a powerful system for practical clinical applications of liquid biopsy.

Cover Art – A high-throughput liquid biopsy platform with a high recovery rate and a high cell viability is realized based on a 2.5D micropore-arrayed filtration membrane.

This article is part of the themed collection: Personalised Medicine: Liquid Biopsy.

Citation: Lab Chip, 2019, 19, 68−78.

 

Wish them promising futures! The farewell party finished successfully

Lingqian Zhang, Xiaolong Rao, Yudan Pi, Xiaofan Zhao, Yuanjian Wu, Haida Li, Yechang Guo and Han Xu graduated from Wangwei Group. We held the farewell party on July 8, 2018.

Group photo of the graduation partyGraduates and prof. Wei Wang at the party. From left to right: Yechang Guo, Yuanjian Wu, Yudan Pi (front), Haida Li, prof. Wei Wang, Lingqian Zhang, Xiaolong Rao, Han Xu.From left to right: Han Xu, Haida Li, Lingqian Zhang, prof. Wei Wang, Yudan Pi, Yuanjian Wu, Yechang GuoGroup photo of our members

To the graduates:

there is life after graduation.

And put forth your best effort in everything you do.

Each graduate is unique.

And we will never say goodbye.

 

Congratulations! Lingqian Zhang Finished Dissertation Defense

Dissertation defense meeting for Ph.D. candidates from EECS, Peking University was held in Micro/Namo Electronics Building on May 31st, 2018. Lingqian Zhang directed by prof. Zhihong Li and prof. Wei Wang has passed her dissertation defense.

Defense meeting committee includes Prof. Shanhong Xia as chairman, Prof. Chengjun Huang, Prof. Chen Zhang, Prof. Dacheng Zhang, Prof. Wengang Wu, Prof. Zhihong Li and Prof. Wei Wang as secretary.