Microfluidic isolation of aptamers with affinity towards multiple myeloma monoclonal immunoglobulins

IF 3 4区医学 Q3 ENGINEERING, BIOMEDICAL

Biomedical Microdevices Pub Date : 2022-12-08 DOI:10.1007/s10544-022-00643-x

Timothy R. Olsen, Claudia Tapia-Alveal, Kechun Wen, Tilla S. Worgall, Milan N. Stojanovic, Qiao Lin

{"title":"Microfluidic isolation of aptamers with affinity towards multiple myeloma monoclonal immunoglobulins","authors":"Timothy R. Olsen, Claudia Tapia-Alveal, Kechun Wen, Tilla S. Worgall, Milan N. Stojanovic, Qiao Lin","doi":"10.1007/s10544-022-00643-x","DOIUrl":null,"url":null,"abstract":"<div><p>Multiple myeloma (MM) is a bone marrow cancer of resident plasma cells that affects 125,000 patients in the U.S. with about 30,000 new cases per year. Its signature is the clonal proliferation of a single plasma cell that secretes a patient specific monoclonal immunoglobulin (M-Ig). Targeting the M-Ig in patient serum could allow sensitive and noninvasive identification of minimal residual disease in multiple myeloma. Aptamers, which are single-stranded oligonucleotides with affinity and specificity to a target molecule, have recently been introduced as affinity reagents for recognition of MM M-Igs. Here we exploit microfluidic SELEX technology to enable rapid and efficient generation of aptamers against M-Ig proteins from MM patients. We first characterize the technology by isolating aptamers with affinity towards the monoclonal antibody rituximab as a model M-Ig and then apply the technology to isolating aptamers specifically targeting M-Igs obtained from serum samples of MM patients. We demonstrate that high-affinity DNA aptamers (K<sub>D</sub> < 50 nM) for M-Ig proteins from a patient sample could be isolated via microfluidic SELEX within approximately 12 h and using less than 100 micrograms of patient M-Ig. Such aptamers can potentially be used in personalized monitoring of minimal residual disease in MM patients.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"25 1","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2022-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Microdevices","FirstCategoryId":"5","ListUrlMain":"https://link.springer.com/article/10.1007/s10544-022-00643-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}

引用次数: 3

Abstract

Multiple myeloma (MM) is a bone marrow cancer of resident plasma cells that affects 125,000 patients in the U.S. with about 30,000 new cases per year. Its signature is the clonal proliferation of a single plasma cell that secretes a patient specific monoclonal immunoglobulin (M-Ig). Targeting the M-Ig in patient serum could allow sensitive and noninvasive identification of minimal residual disease in multiple myeloma. Aptamers, which are single-stranded oligonucleotides with affinity and specificity to a target molecule, have recently been introduced as affinity reagents for recognition of MM M-Igs. Here we exploit microfluidic SELEX technology to enable rapid and efficient generation of aptamers against M-Ig proteins from MM patients. We first characterize the technology by isolating aptamers with affinity towards the monoclonal antibody rituximab as a model M-Ig and then apply the technology to isolating aptamers specifically targeting M-Igs obtained from serum samples of MM patients. We demonstrate that high-affinity DNA aptamers (K_D < 50 nM) for M-Ig proteins from a patient sample could be isolated via microfluidic SELEX within approximately 12 h and using less than 100 micrograms of patient M-Ig. Such aptamers can potentially be used in personalized monitoring of minimal residual disease in MM patients.

Abstract Image

查看原文本刊更多论文

具有多发性骨髓瘤单克隆免疫球蛋白亲和力的适配体的微流控分离

多发性骨髓瘤(MM)是一种常驻浆细胞的骨髓癌，在美国有12.5万名患者，每年约有3万例新病例。其特征是单个浆细胞的克隆增殖，该细胞分泌患者特异性单克隆免疫球蛋白(M-Ig)。靶向患者血清中的M-Ig可以对多发性骨髓瘤的微小残留疾病进行敏感和无创的鉴定。核酸适配体是一种对靶分子具有亲和力和特异性的单链寡核苷酸，最近被引入作为识别MM - M-Igs的亲和试剂。在这里，我们利用微流控SELEX技术能够快速有效地生成针对MM患者M-Ig蛋白的适配体。我们首先通过分离对单克隆抗体利妥昔单抗具有亲和力的适配体作为模型M-Ig来表征该技术，然后将该技术应用于分离从MM患者血清样本中获得的特异性靶向M-Ig的适配体。我们证明了高亲和力DNA适体(KD <50 nM)的M-Ig蛋白可以通过微流控SELEX在大约12小时内分离，使用少于100微克的患者M-Ig。这种适体可以潜在地用于MM患者微小残留疾病的个性化监测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biomedical Microdevices 工程技术-工程：生物医学

CiteScore

6.90

自引率

3.60%

发文量

审稿时长

6 months

期刊介绍： Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology. General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules. Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.