Barcode Particles Research Articles

AIEgens-integrated structural color barcodes for binary screening of microRNAs

Highly sensitive microRNAs (miRNA) imaging is of great value in the early diagnosis of tumors. Here, we present a novel aggregation-induced emission luminogens (AIEgens) integrated structural color barcode for binary screening of miRNAs. The barcode particles consist of periodically ordered silica nanoparticles encoded cores, and tetraphenylethylene carboxylate derivatives TPE-(COOH)4 integrated inverse opal polyacrylamide (PAAm) hydrogel shells. As the miRNA probes are decorated in the adjacent TPE-(COOH)4 molecules, the skeletal networks of the hydrogel as well as the TPE-(COOH)4 molecules would be closer with the presence of target miRNA due to the formation of a double helix. This phenomenon could not only result in fluorescence change of the TPE-(COOH)4 molecules, but also contribute to structural color variation of shell hydrogel. These two optical signals could be employed as binary channels for more accurate detection of target miRNAs. During this process, the solid cores of the barcodes could keep stable structural colors, thus providing foundation codes for multiplexed detection of miRNAs. Based on these features, we have demonstrated that the AIEgens-integrated structural color barcodes could realize the multiplexed screening of miRNAs in a microfluidics device for in vitro diagnosis, which implies the potential prospects in biomedical fields.

Label-free multiplex detection of miRNA-assayed hydrogel barcode using a low-aspect-ratio micropore sensor

We report a rapid and label-free multiplex sensing of target miRNAs using hydrogel barcodes and a low-aspect-ratio micropore device. A 6-bit hydrogel barcode representing codes 0 and 1 was fabricated using flow lithography and functionalized with probe DNA. Subsequently, the probe DNA was assayed with the target miRNA at a specific concentration. The barcode particles in the solution were translocated through a low-aspect-ratio micropore, and the current signal between the cis and trans electrodes was measured. Therefore, the micropore sensor successfully detected the encoded data of the 6-bit hydrogel barcodes. We analyzed signals, such as overshoot, peak drop, and translocation time, to determine the appropriate parameter and subsequently the target miRNA concentration. We observed that the magnitude of the overshoot signal was significantly associated with the concentration of the target miRNA, matched with finite element method (FEM) analysis results. The micropore sensor individually detected the four types of miRNAs in conjunction with the encoded data and achieved a detection limit of 10 pM. In addition, this micropore sensor enabled multiplex sensing of four types of encoded barcodes assayed with different miRNAs in each sample at once.

Droplet microfluidic generation of a million optical microparticle barcodes.

Micron-scale barcode particles enable labelling of small objects. Here, we demonstrate high-throughput barcode fabrication inside a microfluidic chip that can embed multiple, dye-doped high quality-factor whispering gallery mode cavities inside aqueous droplets at kilohertz rates. These droplets are then cured to form polyacrylamide hydrogel beads as small as 30 μm in diameter. Optical resonance spectra of the embedded cavities provide the hydrogels with unique barcodes with their diversity combinatorically scaled with the number of embedded cavities. Using 3 cavities per hydrogel, we obtain approximately one million uniquely identifiable, optically readable barcode microparticles.

Structural color barcodes for biodiagnostics

AbstractSuspension array technology has revolutionized the field of biodiagnostics due to its capability of multiplex assays. Construction of the barcodes is essential, where structural color barcode is one of the most satisfying candidates because of its stable encoding and convenient decoding features. Benefiting from microfluidics technique, structural color barcode particles have been synthesized with finely tuned size, configuration, and surface reactive moieties. This allows for the barcode's interactions with disease‐specific biomarkers at multiscale, from the molecular to the tissue/organ level. In this minireview, we present the very latest progress on structural color barcodes for biodiagnostic applications. We discuss in depth through typical examples of how the sensitive and efficient assays of different types of analytes are accomplished concerning the specific features entailed in the barcodes. We also provide critical thinking about the remaining challenges and future development of structural color barcodes from a biodiagnostics perspective.

Quantum dots integrated biomass pollens as functional multicolor barcodes

Tremendous interests have been aroused in exploring efficient and readily-prepared barcode particles, with information coding and specific identification features, for biomedical analytical applications. Here, we propose a novel type of barcode for optical encoding and fluorescence enhancement via depositing quantum dots (QDs) on natural pollens intermediated by a polyelectrolyte layer. The exquisite prickly surface morphology and an intrinsic high surface-to-volume ratio of the pollens resulted in a fluorescence enhancement, due to which a much lower detection limit was reached. Besides, the easily-tunable fluorescence peak and intensity of QDs and the repeatable deposition process allowed for the generation of coding combinations for the simultaneous determination of multiple targets. These features endow the QD-coated pollens extraordinary barcodes for applications in multiplexed bioassays.

Micropore device for identification of 4-bit hydrogel barcode

We report the precise decoding of a shape-modulated hydrogel barcode particle using a micropore fluidic device. Using an electrical simulation, we deduced the optimal pore geometry that yields the maximal sensing signal. We fabricated hydrogel particles with different dimensions and prepared the micropore device along with a fluidic cell and a patch clamp. Accordingly, we experimentally determined the most appropriate shape of the hydrogel barcode particle that allows efficient differentiation between a 0 code and a 1 code. Thus, we successfully decoded 4-bit hydrogel barcode particles with high speed and high accuracy.

Hollow Colloid Assembled Photonic Crystal Clusters as Suspension Barcodes for Multiplex Bioassays.

Barcode particles have a demonstrated value for multiplexed high-throughput bioassays. Here, a novel photonic crystal (PhC) barcode is presented that consists of hollow colloidal nanospheres assembled through microfluidic droplet templates. Due to their gas-filled core, the resultant barcode particles not only show increased refractive index contrast, but also remain in suspension by adjusting the overall density of the PhC to match that of a detection solution. In addition, magnetic nanoparticles can be integrated to give the barcodes a magnetically controllable motion ability. The encoding ability of the barcodes is demonstrated in microRNA detection with high specificity and sensitivity, and the excellent features of the barcodes make them potentially very useful for biomedical applications.

Emerging barcode particles for multiplex bioassays

With the increasing demand for multiplex and high-throughput analysis of large numbers of biomolecules, multiplex technology becomes a promising tool for carrying out thousands of individual reactions at the same time for large-scale biological analysis. Among current technologies, suspension arrays based on appropriate barcode particles have been popularly used in multiplex bioassays of many research fields with the ability of unique encoding, such as in the clinical, medicinal, nutritional, and environmental fields. Besides the unique form of barcode, these particles have higher flexibility, better sensitivity, and faster reaction kinetics. In this review, we present some examples of typical barcode particles that are divided into different groups depending on how they are encoded and their applications in multiplex bioassays for different targets such as proteins, DNA and RNA sequences, and cells. The bioassays for monitoring food safety, drug research, and clinical diagnosis are also described.

Quantum-dot-encapsulated core-shell barcode particles from droplet microfluidics.

The development of robust quantum dot (QD) barcode particles with specific compositions and simple identification is important to meet the demand for high-throughput assays. Here, we present a multiple-inner phase channel capillary microfluidic approach to generate novel QD-encapsulated core-shell barcode particles with distinctive features for multiplexing analysis. By using different QD dispersed polyethylene glycol diacrylate (PEGDA) solutions as the inner phases, the particles were endowed with hydrogel locked QD cores, which could maintain the dispersed status and provide distinctive identification for the particles. The shells of the barcode particles were silica nanoparticle-dispersed ethoxylated trimethylolpropane triacrylate (ETPTA) resin, which could not only improve the stability and biocompatibility of QDs, but also provide functional groups for immobilization of biomolecules due to the assembling of the silica nanoparticles on their surfaces. Due to the advanced emulsification capability of the capillary microfluidic device, double emulsion templates with multiple inner droplet phases and their resultant multicomponent QD-encapsulated core-shell barcode particles could be continually generated. These particles showed remarkable spectral coding capacity in practice, which make them ideal for biomedical applications.

Fabrication of Multicompartment Particles via Sequential Micromolding Method

본 연구는 순차적인 마이크로 몰딩 방법을 이용한 고분자 다중 분획 입자 제조 방법에 관한 것이다. 다중 분획 입자는 poly(dimethylsiloxane)(PDMS) 마이크로 몰드 내로 단량체 혼합물의 주입, 휘발성 용매의 증발, 광중합으로 이루어지는 일련의 과정을 통해 제조한다. 이때, 단량체 혼합물에 포함된 휘발성 용매의 농도에 따라, 다중 분획입자를 구성하는 각 구획의 부피분율을 제어하는 것이 가능하다. 또한 단량체 혼합물의 농도 및 다중 분획 입자 제조공정의 반복횟수에 따라, 단일 입자, 이중 입자, 삼중 입자를 선택적으로 제조가 가능함을 보여준다. 제조한 각각의 다중 분획 입자에 형광염료를 함입하여 특정한 정보를 인코딩한 바코드 입자로써의 활용 가능성을 증명한다. 본 연구에서 제안하는 다중 분획 입자를 제조하기 위한 순차적인 마이크로 몰딩 방법은 쉽고, 빠르며, 고가의 장비를 필요로 하지 않는 장점을 가지며, 제조된 다중 분획 입자는 약물 저장 및 전달 소재, 바이오 센서, 그리고 선택적인 흡착-탈착을 유도할 수 있는 고감도 기능성 재료로서 응용이 가능할 것으로 기대한다.

Cells Cultured on Core-Shell Photonic Crystal Barcodes for Drug Screening.

The development of effective drug screening platforms is an important task for biomedical engineering. Here, a novel methacrylated gelatin (GelMA) hydrogel-encapsulated core-shell photonic crystal (PhC) barcode particle was developed for three-dimensional cell aggregation culture and drug screening. The GelMA shells of the barcode particles enable creation of a three-dimensional extracellular matrix (ECM) microenvironment for cell adhesion and growth, while the PhC cores of the barcode particles provide stable diffraction peaks that can encode different cell spheroids during culture and distinguish their biological response during drug testing. The applicability of this cell spheroids-on-barcodes platform was investigated by testing the cytotoxic effect of tegafur (TF), a prodrug of 5-fluorouracil (5-FU), on barcode particle-loaded liver HepG2 and HCT-116 colonic tumor cell spheroids. The cytotoxicity of TF against the HCT-116 tumor cell spheroids was enhanced in systems using cocultures of HepG2 and NIH-3T3 cells, indicating the effectiveness of this multiple cell spheroids-on-barcodes platform for drug screening.

Photonic Crystal Microbubbles as Suspension Barcodes.

A novel suspension array was developed that uses photonic crystal (PhC) microbubbles as barcode particles. The PhC microbubbles have an outer transparent polymeric shell, a middle PhC shell, and an inner bubble core, and they were achieved by extraction-derived self-assembly of colloidal nanoparticles in semipermeable solid microcapsules. The encoded elements of the microbubbles originated from their PhC structure with a coated shell, which not only improved the stability of the codes but also provided a flexible surface for bioassays. By using multicompartmental microcapsule templates, PhC microbubbles with substantial coding levels and controllable movement could also be achieved. In addition, as the size of the encapsulated bubbles could be tailored, the overall density of the PhC microbubbles could be adjusted to match the density of a detection solution and to remain in suspension. These remarkable properties make the PhC microbubbles excellent barcode particles.

Microfluidic synthesis of barcode particles for multiplex assays.

The increasing use of high-throughput assays in biomedical applications, including drug discovery and clinical diagnostics, demands effective strategies for multiplexing. One promising strategy is the use of barcode particles that encode information about their specific compositions and enable simple identification. Various encoding mechanisms, including spectroscopic, graphical, electronic, and physical encoding, have been proposed for the provision of sufficient identification codes for the barcode particles. These particles are synthesized in various ways. Microfluidics is an effective approach that has created exciting avenues of scientific research in barcode particle synthesis. The resultant particles have found important application in the detection of multiple biological species as they have properties of high flexibility, fast reaction times, less reagent consumption, and good repeatability. In this paper, research progress in the microfluidic synthesis of barcode particles for multiplex assays is discussed. After introducing the general developing strategies of the barcode particles, the focus is on studies of microfluidics, including their design, fabrication, and application in the generation of barcode particles. Applications of the achieved barcode particles in multiplex assays will be described and emphasized. The prospects for future development of these barcode particles are also presented.

Aptamer-functionalized barcode particles for the capture and detection of multiple types of circulating tumor cells.

Aptamer-functionalized barcode particles are employed to capture and detect various types of circulating tumor cells (CTCs). The particles are spherical colloidal crystal clusters, and the reflection properties that arise from their structures are how their codes are evaluated. Aptamer functionalization (with TD05, Sgc8, and Sgd5) make the particles interact with specific CTC types; dendrimers are used to amplify the effect of the aptamers, allowing for increased sensitivity, reliability, and specificity in CTC capture, detection, and subsequent release.

Convenient generation of quantum dot-incorporated photonic crystal beads for multiplex bioassays.

Barcode particles have a demonstrated value for multiplexed bioassays in clinical diagnostics, drug discovery, and so on. Attempts to develop this technology are focusing on the generation of novel particles with a large number of identifications to increase the throughput of the assays. Here we report a new type of barcode particles with quantum dot (QD)-photonic crystal (PC) joint spectrum encoding. These barcode particles are simply prepared by in-situ polymerization of CdTe QDs-contained acrylamide pre-gel in the colloidal photonic crystal beads (PCBs). By encapsulating different wavelength-and-intensity QDs into the PCBs with various-reflection spectra, thousands of available barcode particles could be obtained. Moreover, by employing magnetic nanoparticles into the PCBs, the achieved barcode particles could be conferred a function of controllable movement under magnetic field. This feature could significantly increase the sensitivity and simplify the processing of the bioassays.

Multifunctional photonic crystal barcodes from microfluidics

Biological systems are often studied through the use of assays, in which different experimental parameters are varied systematically. One method uses so-called barcode particles to track different samples. However this approach is complicated by the difficulty of producing barcode systems that allow for a sufficient number of configurations. Zhongze Gu and colleagues from Southeast University in Nanjing, China, have now developed a barcode system based on photonic crystals. These crystals, whose color reflection can be controlled during fabrication, are prepared with the help of a microfluidic system that also enables the simultaneous incorporation of the biomolecules to be probed. The barcodes particles also contain a magnetic tagged component that allows them to be moved in a magnetic field for easier read-out. By combining several types of photonic crystals in one unit, up to 1.28 million marker combinations are possible.

Microfluidic Generation of Multifunctional Quantum Dot Barcode Particles

We develop a new strategy to prepare quantum dot (QD) barcode particles by polymerizing double-emulsion droplets prepared in capillary microfluidic devices. The resultant barcode particles are composed of stable QD-tagged core particles surrounded by hydrogel shells. These particles exhibit uniform spectral characteristics and excellent coding capability, as confirmed by photoluminescence analyses. By using double-emulsion droplets with two inner droplets of distinct phases as templates, we have also fabricated anisotropic magnetic barcode particles with two separate cores or with a Janus core. These particles enable optical encoding and magnetic separation, thus making them excellent functional barcode particles in biomedical applications.