Self-organizing magnetic beads for biomedical applications

In the field of biomedicine magnetic beads are used for drug delivery and to treat hyperthermia. Here we propose to use self-organized bead structures to isolate circulating tumor cells using lab-on-chip technologies. Typically blood flows past microposts functionalized with antibodies for circulating tumor cells. Creating these microposts with interacting magnetic beads makes it possible to tune the geometry in size, position and shape. We developed a simulation tool that combines micromagnetics and discrete particle dynamics, in order to design micropost arrays made of interacting beads. The simulation takes into account the viscous drag of the blood flow, magnetostatic interactions between the magnetic beads and gradient forces from external aligned magnets. We developed a particle-particle particle-mesh method for effective computation of the magnetic force and torque acting on the particles

New generation of electrochemical immunoassay based on polymeric nanoparticles for early detection of breast cancer

Screening and early diagnosis are the key factors for the reduction of mortality rate and treatment cost of cancer. Therefore, sensitive and selective methods that can reveal the low abundance of cancer biomarkers in a biological sample are always desired. Here, we report the development of a novel electrochemical biosensor for early detection of breast cancer by using bioconjugated self-assembled pH-responsive polymeric micelles. The micelles were loaded with ferrocene molecules as "tracers" to specifically target cell surface-associated epithelial mucin (MUC1), a biomarker for breast and other solid carcinoma. The synthesis of target-specific, ferrocene-loaded polymeric micelles was confirmed, and the resulting sensor was capable of detecting the presence of MUC1 in a sample containing about 10 cells/mL. Such a high sensitivity was achieved by maximizing the loading capacity of ferrocene inside the polymeric micelles. Every single event of binding between the antibody and antigen was represented by the signal of hundreds of thousands of ferrocene molecules that were released from the polymeric micelles. This resulted in a significant increase in the intensity of the ferrocene signal detected by cyclic voltammetry

Biomedical applications of magnetic hydrogels

Hydrogels are used in biomedical applications thanks to their high-water content, porosity, and their ability to easily modify their properties (mechanical, chemical, microstructure, etc.). Hydrogels are the materials that most resemble the extracellular matrix of mammals. In recent years, magnetic hydrogels have become especially important. These are the result of combining magnetic nanoparticles with different hydrogel matrices. Among its properties, they have the ability to be remotely controlled modifying their physical properties, such as stability, stiffness and temperature (magnetic hyperthermia). Such unique characteristics make magnetic hydrogels very promising in biomedical applications such as, tissue engineering, drug delivery, biosensors, and cancer therapy. At this respect, this chapter focuses on the main biomedical applications of magnetic hydrogels and the most important discoveries on the subject.This study was supported by project FIS2017?85954-R (Ministerio de Economía, Industria y Competitividad, MINECO, and Agencia Estatal de Investigación, AEI, Spain, cofunded by Fondo Europeo de Desarrollo Regional, FEDER, European Union). CGV acknowledges financial support by Ministerio de Ciencia, Innovación y Universidades and University of Granada, Spain, for her FPU17/00491 grant

Microtransformers: controlled microscale navigation with flexible robots

Artificial microswimmers are a new technology with promising microfluidics and biomedical applications, such as directed cargo transport, microscale assembly, and targeted drug delivery. A fundamental barrier to realising this potential is the ability to control the trajectories of multiple individuals within a large group. A promising navigation mechanism for "fuel-based" microswimmers, for example autophoretic Janus particles, entails modulating the local environment to guide the swimmer, for instance by etching grooves in microchannels. However, such techniques are currently limited to bulk guidance. This paper will argue that by manufacturing microswimmers from phoretic filaments of flexible shape-memory polymer, elastic transformations can modulate swimming behaviour, allowing precision navigation of selected individuals within a group through complex environments

Microengineering Aligned Collagen Substrates In Microfluidic Systems

Cells in vivo are surrounded by a fibrous matrix of proteins and macromolecules called the extracellular matrix (ECM), of which type I collagen is the major constituent. During tissue development or cell-matrix interactions, collagen fibers organize into aligned domains with defined degrees of alignment and directionality. Aligned fibers guide stem cell differentiation and influence cell-cell communication and cell motility. In the tumor microenvironment, aligned fibers guide tumor cell invasion and have been linked to poor patient outcomes. Since fiber alignment instructs cell behavior in vivo, there is a need for in vitro models to replicate fiber alignment and thus provide a relevant microenvironment for cells. Microfluidic systems have been established as advanced cell culture platforms to provide precise control over soluble factor concentration, cell patterning, and fluid flow. However, controlling the fiber alignment of a 3D material within them has remained a challenge. This work addresses existing technological challenges to integrate 3D collagen matrices with aligned fibers into microfluidic platforms. To do so, this work i) Demonstrates for the first time that extensional flows can align 3D collagen matrices (250 µm thick) in a microchannel, ii) Develops modular microfluidic platforms with capabilities to directly access and perfuse 3D collagen, and iii) Develops biofabrication capabilities to create interfaces between different ECM materials in 3D, and create tissue barriers using ultrathin nanomembranes. It is anticipated that the novel ECM microengineering capabilities and approach to integrating the engineered matrices into microfluidic devices will provide a path to develop tissue-specific in vitro models with engineered matrices