Quantifying spatio-temporal dynamics of biomarker pre-concentration and depletion in microfluidic systems by intensity threshold analysis

Abstract

Microfluidic systems are commonly applied towards pre-concentration of biomarkers for enhancing detection sensitivity. Quantitative information on the spatial and temporal dynamics of pre-concentration, such as its position, extent, and time evolution are essential towards sensor design for coupling preconcentration to detection. Current quantification methodologies are based on the time evolution of fluorescence signals from biomarkers within a statically defined region of interest, which does not offer information on the spatial dynamics of pre-concentration and leads to significant errors when the pre-concentration zone is delocalized or exhibits wide variations in size, shape, and position over time under the force field. We present a dynamic methodology for quantifying the region of interest by using a statistical description of particle distribution across the device geometry to determine the intensity thresholds for particle pre-concentration. This method is applied to study the delocalized pre-concentration dynamics under an electrokinetic force balance driven by negative dielectrophoresis, for aligning the pre-concentration and detection regions of neuropeptide Y, and for quantifying the polarizability dispersion of silica nano-colloids with frequency of the force field. We envision the application of this automated methodology on data from 2D images and 3D Z-stacks for quantifying pre-concentration dynamics over delocalized regions as a function of the force field. V C 2014 AIP Publishing LLC.

Nanoslit design for ion conductivity gradient enhanced dielectrophoresis for ultrafast biomarker enrichment in physiological media

“…For the case of nanoslits with 130 nm constrictions, the profiles are somewhat similar (Figures 4(f)-4(h)), with initial preconcentration along constriction sidewalls and a biomarker depletion region along the centerline. However, the preconcentration is considerably slower, as apparent from the longer time intervals, 32 and the biomarker depletion region extends no more than $3 lm along the centerline. For the case of trapping under nDEP conditions with a sub-critical DC field for initiating ICP, the biomarker enrichment rate is gradual (Figure 4(k)) and the trapping profile shows only a very small biomarker depletion region ($0.3 lm along centerline in Figure 4(e)).…”

Preface to Special Topic: Selected Papers from the Advances in Microfluidics and Nanofluidics 2014 Conference in Honor of Professor Hsueh-Chia Chang's 60th Birthday

“…This special issue is dedicated to Professor Hsueh-Chia Chang in honor of his 60th birthday and comprised the original contributions that were presented at the conference. The topics cover a wide range of research efforts from both fundamental science and practical applications of microfluidics and nanofluidics, including biosensors and diagnosis for clinical testing, [1][2][3][4] cell and evolution studies, [5][6][7][8][9][10] advanced bioimaging/optical technologies, 11,12 droplet microfluidics, 13,14 bilayer lipid membrane, 14,15 micro-and nanofabrications, [16][17][18][19][20][21] and environmental and drug screening applications. 22,23 Integrated microfluidic devices for replacing traditional clinical tests have seen significant recent advances.…”

“…18 Rohani et al revealed a method of quantifying spatio-temporal dynamics of biomarker pre-concentration and depletion in microfluidic systems by intensity threshold analysis. 19 Chou's group developed a new DNA combing platform using low-pressure oxygen plasma modified polysilsesquioxane substrates for single-molecule studies and used it to observe DNA-protein complexes and the effect of cancer drug cisplatin on DNA conformation. 20 With the aid of a simulation study, Yoon et al proposed a new way of measuring fluid interfacial nanoroughness through the morphological characteristics of graphene.…”

Microfluidic Device Design for Selective Enrichment of Biocolloids Based on their Deformability and Polarization

“…[1][2][3][4]57] In order to utilize this scheme, an array of insulating micro-or nanoconstrictions are integrated within a nanoslit platform and are used as force lenses to create field non uniformities in an AC electric field applied over the nanoslit. The frequency of the AC field is chosen such that the target analyte undergoes nDEP and is thus translated away from the high field points at the [4] tips of the nanoconstrictions.…”