Name: biomems in diagnostics and miniaturization
Uploaded: 2023-04-30T06:32:23.000Z
Duration: 8 min 28 s
Channel: JoVE

<div class="chapter_text" id="script_0">
通过使用微量样品和试剂以及并行处理，将分析设备微型化至微米尺度可节省时间和成本。这些微型仪器被称为生物微机电系统（Bio Micro-Electro-Mechanical Devices），也称为 BioMEMs。BioMEMs 可作为体内或体外的微型诊断设备，能够执行取样、过滤、反应或检测等多种功能。此外，其尺寸特征使得分析设备的灵敏度和选择性得到提高。本视频将介绍科研中常用的 BioMEMs 设备、主要的制备方法以及该领域面临的关键挑战。
</div>
<div class="chapter_text" id="script_1">
生物微机电系统&#160;设备通常在洁净室中利用微加工技术制造，至少有一个维度处于微米尺度。制造完成后，该设备将集成到更大的仪器系统中。常见的生物微机电系统&#160;设备为微全分析系统，也称为芯片实验室。这些系统可完成特定分析的全部或部分流程。例如，微流控设备就是芯片实验室系统中最常见的类型之一。微流控设备在芯片上具有微尺度通道，能够利用微量样品体积实现分离、反应和检测。由于其微尺度的结构特征，这些设备采用压力驱动流动。&#160;或通过毛细作用将分析物或试剂输送通过通道。由于系统采用层流，物质传递和混合依赖于扩散。相较于湍流（其混合过程混乱且不规则），层流更受青睐。此外，微流控系统的微小尺寸使其在使用表面固定化催化剂或酶的体系中具有较高的表面积与体积比，从而促进流体流中分析物与表面固定组分之间的增强相互作用。最后，由于其尺寸微小，可实现快速且均匀的热传递，从而在样品加热过程中实现更佳的控制性和均匀性。因此，这类系统被广泛应用于多种诊断场景，甚至可用于制备微粒。在我们介绍了生物微机电系统（BioMEMs）之后，接下来将探讨其典型的 fabrication（制备）方法。
</div>
<div class="chapter_text" id="script_2">
生物微机电系统（BioMEMs）中最常用的材料，尤其是集成电路器件，是硅。硅晶圆通常作为基底材料，其表面可加工出各种形状和图案，甚至可将结构刻蚀到表面内部。聚合物也常被使用，因为它们成本较低，且在某些情况下更易于操作和制备。聚合物可通过注塑成型、压印或复制成型实现复杂结构的简单复制。最后，金属被集成到生物微机电系统中，以改善微尺度电路的制造。金、银和铬等金属通过电镀或蒸发法分层沉积。大多数复杂的微结构采用光刻技术制造，该技术利用光在基底上形成图案。基底通常是硅晶圆，首先在其表面涂覆一种对紫外光敏感的物质，称为光刻胶。然后通过紫外光将掩模上的图案转移到已涂覆的基底上。经过一系列加工步骤后，该图案被永久刻蚀到硅基底中，形成三维结构。另一种常与光刻技术结合使用的技术是软光刻。软光刻是一种利用聚合物复制三维结构的技术。之所以称为“软”光刻，是因为通常使用弹性体聚合物。最常用的弹性体是聚二甲基硅氧烷（PDMS）。PDMS是一种基于硅的弹性体，具有光学透明、无毒、惰性的特性。将PDMS直接浇注在微结构上，随后进行脱气和固化。该技术能够在无需复杂或昂贵加工步骤的情况下实现复杂结构的复制。
</div>
<div class="chapter_text" id="script_3">
尽管制备方法已较为成熟，但在制备和使用BioMEM&#160;器件时仍存在诸多挑战。首先，BioMEM&#160;器件采用亚微米级结构，当结构极为复杂或需要多层加工时，制造难度较大。微型化还会带来在宏观尺度下不会出现的物理挑战。例如，由于尺寸微小，表面粗糙度、通道直径或器件内组装分子的缺陷会被放大，从而影响器件功能。另一个挑战是污染问题。BioMEM&#160;器件必须与环境接触，但同时又需避免环境对其造成影响。灰尘、非目标生物分子或其他微粒极易污染微尺度结构，导致器件功能下降甚至完全失效。因此，最好在洁净室环境中制造这些器件，以最大限度减少污染。这些微型系统有时仅作为概念验证器件使用，后续需放大以适应大体积样品或分析物的检测。然而，这可能带来显著挑战。例如，将微流控器件放大至更大尺寸时，流体流动和传质行为将发生显著变化，导致原本在微尺度下实现的理想结果无法在宏观尺度重现，从而限制了放大过程的应用，通常只能通过并行使用多个小型器件来实现规模化。
</div>
<div class="chapter_text" id="script_4">
生物微机电系统（BioMEM&#160;）器件在生物分析研究的多种应用中被广泛使用。例如，微流控器件可作为极小体积的生物反应器。在本研究中，一个皮升级的生物反应器被用于单细胞分析。单个细胞进入反应腔室后，能够在其中生长和分裂。随着细胞总体密度在生长过程中增加，单个细胞通过微小通道离开反应器，从而实现单细胞分析。这使得研究人员能够在单细胞水平上直接测量细胞生长速率、形态特征以及表型异质性。微流控技术还可用于实现生物分子及其他微尺度组分的快速分离。在此示例中，采用分支式微流控器件对尺寸相近的微珠和细胞进行分离。将微珠和细胞注入通道后，将器件连接至电源以施加电场。在未施加电场时，微珠流经所有通道；而一旦电场开启，微珠仅被引导进入其中一条通道。利用该技术，可将微珠与细胞的混合物分流入不同的通道中实现分离。最后，生物微机电系统（BioMEM&#160;）器件也常被用作微型生物电子器件。在此示例中，一种微米级的场效应晶体管（FET）被构建出来。FET利用电场调控器件中半导体材料的电导率。该FET通过硅纳米线和探针分子进行功能化修饰，使其对环境变化具有敏感性，随后被用于检测DNA或生物标志物等生物靶标。
</div>
<div class="chapter_text" id="script_5">
您刚刚观看了 JoVE 关于生物微机电系统（BioMEMs）的概述。现在您应该了解了什么是生物微机电系统、常用的制造技术、其面临的挑战以及它们在生物工程领域的应用。感谢观看。
</div>

生物微机电系统设备概述

Overview of BioMEM Devices

生物微机电系统（BioMEMs）是一类微米级装置，可利用微量样本和试剂体积用于诊断设备 体内 和 体外这些装置可在微尺度上执行过滤、传感或合成等多种功能，从而降低成本并提高灵敏度。
本视频介绍了生物微机电系统（BioMEMs），探讨了其在生物工程领域的应用，并展示了 fabrication 中的一些主要方法。此外，视频还讨论了设备微型化过程中存在的一些关键挑战，以及该技术的一些应用。

生物微机电系统，也称为BioMEMs，是一类微米级装置，可利用微量样本和试剂体积用于诊断设备。 体内 和 体外这些装置可在微尺度上执行过滤、传感或合成等多种功能，从而降低成本并提高灵敏度。
本视频介绍了生物微机电系统（BioMEMs），探讨了其在生物工程领域的应用，并展示了 fabrication 中的一些主要方法。此外，视频还讨论了设备微型化过程中存在的一些关键挑战，以及该技术的一些应用。

生物微机电系统，也称为BioMEMs，是一类微米级装置，可利用微量样本和试剂进行诊断……

通过使用微量的样品和试剂，并结合并行处理，将分析设备微型化至微米尺度，可节省时间和成本。这些微型仪器被称为生物微机电系统（Bio Micro-Electro-Mechanical Devices），简称BioMEMs。BioMEMs可作为微型化的体内外诊断设备，能够执行取样、过滤、反应或检测等多种功能。此外，其微小尺寸可提高分析设备的灵敏度和选择性。本视频将介绍科研中常用的BioMEMs设备、主要的制备方法以及该领域面临的关键挑战。生物微机电系统（BioMEM?）设备通常在洁净室中采用微加工技术制造，且至少有一个维度处于微米尺度。制造完成后，该设备会与更大的仪器集成。常见的生物微机电设备包括“微全分析系统”，也称为“芯片实验室”（Lab-on-a-chip）。这些系统可完成全部或部分特定分析任务。例如，微流控设备就是最常见的一类芯片实验室系统。微流控设备在芯片上具有微米级通道，能够利用微量样品体积实现分离、反应和检测。由于其微米级的尺寸特征，这些设备依靠压力驱动流动或毛细作用来输送分析物或试剂通过通道。由于系统内为层流，传质和混合过程主要依赖扩散，这优于湍流条件下混乱且不规则的混合方式。此外，微尺度结构使得在使用表面固定催化剂或酶的系统中具有较高的表面积与体积比，从而促进流体流中分析物与表面结合组分之间的相互作用增强。最后，由于其尺寸微小，可实现快速且均匀的热传递，从而在样品加热过程中实现更佳的控制性和均匀性。因此，这些系统被广泛应用于多种诊断场景，甚至可用于制备微粒。在我们介绍了生物微机电系统之后，接下来让我们看看它们通常是如何制造的。生物微机电系统（BioMEMs）中最常用的材料，尤其是集成电路器件，是硅。硅晶圆通常用作基底材料，在其表面之上创建形状和图案，甚至直接在表面进行刻蚀。聚合物也常被使用，因为它们成本较低，且在某些情况下更易于操作和制备。聚合物可通过注塑成型、压印或复制模塑实现复杂结构的简单复制。最后，金属被集成到生物微机电系统中，以改善微尺度电路的制造。金、银和铬等金属通过电镀或蒸发法分层沉积。大多数复杂的微结构采用光刻技术制造，该技术利用光在基底上形成图案。基底通常是硅晶圆，首先涂覆一层对紫外光敏感的物质，称为光刻胶。然后通过紫外光将掩模上的图案转移到已涂覆的基底上。经过一系列加工步骤后，该图案被永久刻蚀到硅基底中，形成三维结构。另一种常与光刻技术结合使用的技术是软光刻。软光刻是一种利用聚合物复制三维结构的技术。之所以称为“软”光刻，是因为通常使用弹性体聚合物。最常用的弹性体是聚二甲基硅氧烷（PDMS）。PDMS是一种基于硅的弹性体，具有光学透明、无毒、惰性的特性。将PDMS直接浇注在微结构上，随后进行脱气和固化。该技术能够在无需复杂或昂贵加工步骤的情况下实现复杂结构的复制。尽管制造方法已相当成熟，但在制备和使用BioMEM?器件时仍存在诸多挑战。首先，BioMEM?器件采用亚微米级结构，当结构极为复杂或需要多层叠加时，加工难度较大。微型化还会带来在宏观尺度下不会出现的物理挑战。例如，由于器件尺寸微小，表面粗糙度、通道直径或器件内组装分子的缺陷会被显著放大，从而影响器件功能。另一个挑战是污染问题。BioMEM?器件必须与环境接触，但同时又需避免环境对其造成影响。灰尘、非目标生物分子或其他微粒极易污染微尺度结构，导致器件功能下降甚至完全失效。因此，最好在洁净室环境中制造这些器件，以最大限度减少污染。这些微型系统有时仅作为概念验证器件使用，最终需放大以适应大体积样品或分析物的检测。然而，这一放大过程可能面临重大挑战。例如，将微流控器件按比例放大至更大尺寸时，流体流动和传质行为将发生显著变化，导致原本在微尺度下实现的理想结果无法在宏观尺度重现，从而限制了放大应用，只能通过并行使用多个小型器件来实现规模化。生物微机电系统（BioMEM?）设备在生物分析研究的广泛应用中发挥着重要作用。例如，微流控设备可被用作极小体积的生物反应器。在本研究中，皮升级生物反应器被用于单细胞分析。单个细胞进入反应室后，能够在其中生长并分裂。随着细胞密度在生长过程中逐渐增加，单个细胞通过微小通道离开反应器，从而实现对单个细胞的分析。该方法可直接在单细胞水平上测量细胞生长速率、形态特征以及表型异质性。微流控技术还可用于实现生物分子及其他微尺度组分的快速分离。在此示例中，采用分支式微流控装置对尺寸相近的微珠和细胞进行分离。将微珠和细胞注入通道后，将装置连接至电源以施加电场。在未施加电场时，微珠会流经所有通道；而一旦开启电场，微珠则仅通过其中一个通道。利用该技术，可将微珠与细胞的混合物分离至不同通道中。最后，生物微机电系统设备也常被用作微型生物电子器件。在此示例中，研究人员在微米尺度上构建了一种场效应晶体管（FET）。场效应晶体管利用电场调控器件中半导体材料的电导率。该FET通过硅纳米线和探针分子进行功能化修饰，使其对环境变化具有敏感性，随后被用于检测DNA或生物标志物等生物靶标。您刚刚观看了 JoVE 关于生物微机电系统（BioMEMs）的概述。现在，您应该了解了什么是生物微机电系统、一些常用的制造技术、其所面临的挑战以及它们在生物工程领域的应用。感谢观看。

Education

教育

JoVE Science Education

Engineering

工程学

Bioengineering

生物工程

BioMEM 设备概述

biomems in diagnostics and miniaturization

Bio-microelectromechanical systems, or BioMEMs, are microscale devices used in diagnostic settings. They work with very small sample and reagent volumes in vivo and in vitro, which means inside a living body or outside it in a lab. These compact systems support bioengineering research and help make diagnostic tools more efficient.

BioMEMs can carry out functions such as filtration, sensing, and synthesis on a tiny scale. Using less material can lower costs and improve sensitivity. The technology also depends on fabrication methods designed for small, precise structures.

Miniaturizing devices creates important design challenges, and those issues are part of BioMEM research. The field also includes many practical uses of these systems. BioMEMs continue to play a growing role in diagnostics and other bioengineering applications.

BioMEMs in Diagnostics and Miniaturization

biomems-in-diagnostics-and-miniaturization

overview of biomaterials

Biomaterials in Medicine and Engineering

Biomaterials are materials designed to interact well with biological organisms or molecules. They may come from an organism, be produced by an organism, or be made as a synthetic polymer. Because of these properties, engineers use biomaterials in medicine and other biological applications. These materials are used in tissue engineering, biosensing, and drug delivery. Tissue engineering uses materials to support the growth or repair of tissues. Biosensing uses materials to detect biological...

collagen hydrogels

Porcine Collagen for Tissue Engineering

Collagen is a useful biomaterial with uses that go beyond the lab. It has also found commercial use in photography. In tissue engineering, collagen can be turned into hydrogels that give engineered tissue support and structure. This page follows the path from porcine skin to a collagen hydrogel. Porcine skin is used as the source of collagen. The material is then prepared for use in tissue engineering applications. The video also shows several applications of collagen and the methods used to...

electrospinning of silk biomaterials

Silk Cocoon Processing for Fiber Mats

Silk cocoons can be processed into a soluble material that is useful for making biomaterials. Silk fibers have been used for fabrics and threads for centuries, but turning them into a versatile pre-polymer solution is a newer technique. That solution can then be shaped into materials with controllable mechanical properties. The process begins with silk worm cocoons. The silk is solubilized, or dissolved, so it can be handled as a liquid-like solution. The video then shows how that silk...

overview of biomem devices

Bio-microelectromechanical systems, or BioMEMs, are microscale devices used in diagnostic settings. They work with very small sample and reagent volumes in vivo and in vitro, which means inside a living body or outside it in a lab. These compact systems support bioengineering research and help make diagnostic tools more efficient. BioMEMs can carry out functions such as filtration, sensing, and synthesis on a tiny scale. Using less material can lower costs and improve sensitivity. The...

microfabrication via photolithography

Photolithography for Silicon Wafer Patterning

Photolithography is a common microfabrication method used to pattern a silicon wafer. It uses light to transfer a design onto the wafer surface. This process helps form the basis for many BioMEM devices. The page also shows how photolithography is carried out in a cleanroom. Cleanroom steps are important because they support careful fabrication of small, detailed features. The video ends by introducing applications of this process in BioMEM device production.

soft lithography

Photolithography for Microfluidic Device Making

Photolithography and soft lithography are used to make BioMEM devices such as microfluidic channels. A microscale pattern is copied by curing an elastomeric polymer over a 3D structure. The result is a polymer piece that can serve as part of a biological device. These polymer structures are then used to build a range of tools. Some are microfluidic channels for biosensing applications. Others are microscale bioreactors that let scientists visualize micro-colonies. The process also shows how...

overview of bioprocess engineering

Bioreactors and Protein Production in Bioprocessing

Bioprocessing uses living organisms to make a desired target product. In many cases, that product is a protein made in a bioreactor, which is a controlled vessel for growing cells. This process often relies on genetically engineered organisms. Engineers design the system so the cells can produce proteins at large scale. That approach is central to making biotherapeutics, which are drugs made from biological materials. Biotherapeutics are important medicines for complex diseases such as...

synthetic biology

Engineering Cells to Produce Proteins

Synthetic biology is a bioengineering method for programming cells to make useful products. In many cases, the goal is to genetically modify an organism so it can produce large amounts of a protein. That protein may already be made by the cell, or it may come from a newly inserted DNA sequence. The process depends on changing an organism’s genetic material. This is done with transformation or transfection, two common ways to introduce DNA into cells. The video also shows how this work is...

batch and continuous bioreactors

Growing Cells in Bioreactors

Bioreactors are used to grow organisms in large volumes. This makes it possible to produce large amounts of a target product. In laboratory and bioengineering settings, they provide a controlled place for cell growth and product formation. The two main reactor types are batch reactors and continuous reactors. A batch reactor contains all of the materials needed for cell growth at the start. A continuous reactor has inlet and outlet ports, so fresh growth media can be added while cell waste is...

overview of biosensing

How Biosensors Detect Molecules

Biosensors detect biological molecules and chemical contaminants by combining biology with physical measurement. They can identify targets such as proteins or cells, as well as non-biological molecules like chemicals or contaminants. This makes biosensing a useful field for studying and monitoring many kinds of samples. These devices rely on different signal types to find the target molecule. Some biosensors use electrical signals, while others depend on optical, electrochemical, or mechanical...

electrochemical biosensing

Glucose Sensors and Cancer Detection

Electrochemical biosensors detect target molecules by measuring an oxidation-reduction event. That signal changes when a molecule binds to the sensor surface. These sensors helped shape modern biosensing after the first glucose biosensor was invented. The glucose biosensor is a key example of this technology. It shows how electrochemical sensing can track a biological target through a measurable electrical change. The same basic idea also helps explain how electrochemical biosensors can be...

optical biosensing

Detecting Molecules with Light

Optical biosensors detect target molecules with light. They monitor binding by reading an optical signal from the sample. This makes them useful for seeing when a target molecule is present. Some optical biosensors use a label molecule. The label creates a measurable signal, such as fluorescence. Other optical biosensors are label-free and track changes in optical properties, such as refractive index, as binding occurs. This page introduces both label and label-free optical biosensors. It...

overview of tissue engineering

Building Artificial Tissue with Biomaterials

Tissue engineering uses biomaterials, specific cells, and growth factors to build artificial tissue. These engineered tissue constructs are designed for tissue repair and, in some cases, organ replacement. The field focuses on how to make tissue work like natural tissue. It begins with a scaffold, which is a structure that supports cell growth. Cells are then added to the scaffold, and growth factors help encourage proliferation, or cell multiplication. The video also outlines common methods...

histotypic tissue culture

3D Cell Growth on Engineered Matrices

Histotypic tissue culture uses an engineered three-dimensional matrix to grow and propagate cells. Compared with common two-dimensional tissue culture, cells in a 3D setting behave more realistically and better mimic native tissue. The method is useful when high cell density is needed. The process begins by harvesting cells from donor tissue. Those cells are then placed onto an engineered construct for culture. This setup supports growth in a three-dimensional space instead of a flat surface.

whole organ tissue culture

Lung Decellularization and Recellularization

Whole organs can be cultured ex vivo using specialized bioreactors to support repair or replacement of entire organs. In this approach, a donor organ is first stripped of all cells. What remains is the three-dimensional structure of the organ, which can then be repopulated with new cells. The lung is the example shown here. The method uses a dynamic culture system that provides mechanical stimulation, similar to what the organ experiences in the body. This type of culture helps induce native...

bioengineering

该系列涵盖了核心生物工程概念, 包括生物材料的生产、histotypic 和整个器官组织培养、生物技术, 以及 bioMEMs 和传感的复杂系统级领域。

Explore BioMEMs, microscale devices used in diagnostics, bioengineering, and fabrication. Learn how miniaturization affects sensing, filtration, and synthesis.

BioMEMs in Diagnostics and Miniaturization

Description

Transcript

Tags