Integrated microfluidic array plate (iMAP) for cellular and molecular analysis

Abstract

Just as the Petri dish has been invaluable to the evolution of biomedical science in the last 100 years, microfluidic cell assay platforms have the potential to change significantly the way modern biology and clinical science are performed. However, an evolutionary process of creating an efficient microfluidic array for many different bioassays is necessary. Specifically for a complete view of a cell response it is essential to incorporate cytotoxic, protein and gene analysis on a single system. Here we present a novel cellular and molecular analysis platform, which allows access to gene expression, protein immunoassay, and cytotoxicity information in parallel. It is realized by an integrated microfluidic array plate (iMAP). The iMAP enables sample processing of cells, perfusion based cell culture, effective perturbation of biologic molecules or drugs, and simultaneous, real-time optical analysis for different bioassays. The key features of the iMAP design are the interface of on-board gravity driven flow, the open access input fluid exchange and the highly efficient sedimentation based cell capture mechanism (~100% capture rates). The operation of the device is straightforward (tube and pump free) and capable of handling dilute samples (5-cells per experiment), low reagent volumes (50 nL per reaction), and performing single cell protein and gene expression measurements. We believe that the unique low cell number and triple analysis capabilities of the iMAP platform can enable novel dynamic studies of scarce cells.

High-throughput screening approaches and combinatorial development of biomaterials using microfluidics

“…Commonly, designs of systems with multiple chambers allow parallel readouts from individualized cell populations, through independent experiments. For example, an integrated microfluidic array plate was proposed by Dimov et al [37] where cytotoxicity, real-time nuclei acid sequence-based amplification and immunofluorescent protein expression detection were performed in parallel. Yang et al [38] proposed a system creating a 3D hypoxic microenvironment that enabled efficient quantification of human neuronal stem cell self-renewal and differentiation alterations, as an alternative to 2D and 3D hydrogel-based macro culture systems.…”

Recent Developments in Cell-Based Microscale Technologies and Their Potential Application in Personalised Medicine

“…The widened section of the flow channel reduces the flow velocity, providing sufficient time for cells to irreversibly sediment into the trench. This is a highly efficient, merely sedimentation-based cell capture method, whereby experiments with HeLa and MCF7 cells show capture efficiencies close to 100% at flow velocities of 20 µm s -1 (Dimov et al, 2011). Cell loading onto the chip and flow velocities within the microfluidic channels are controlled by fluid levels within a pipette tip at the inlet of the chip.…”

Gravity-oriented microfluidic device for uniform and massive cell spheroid formation

“…1(d4)). [16][17][18] Due to R D ) R A , R B , R C , R E , the input medium is evenly perfused. 15,19 Lastly, if retrieval of the cell spheroids is required, they can be extracted from the trap chambers by applying reverse flow from port 4 to port 1 ( Fig.…”