There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Research data show that more resistant stem cells than common cancer cells exist in cancer patients.To identify unrecognized differences between cancer stem cells and cancer cells might be able to develope effective classification,diagnose and treat ment for cancer.

Stem Cells,Cancer and Cancer Stem Cells

Accurate and high throughput cell sorting is a critical enabling technology in molecular and cellular biology, biotechnology, and medicine While conventional methods can provide high efficiency sorting in short timescales, advances in microfluidics have enabled the realization of miniaturized devices offering similar capabilities that exploit a variety of physical principles We classify these technologies as either active or passive Active systems generally use external fields (eg, acoustic, electric, magnetic, and optical) to impose forces to displace cells for sorting, whereas passive systems use inertial forces, filters, and adhesion mechanisms to purify cell populations Cell sorting on microchips provides numerous advantages over conventional methods by reducing the size of necessary equipment, eliminating potentially biohazardous aerosols, and simplifying the complex protocols commonly associated with cell sorting Additionally, microchip devices are well suited for parallelization, enabling complete lab-on-a-chip devices for cellular isolation, analysis, and experimental processing In this review, we examine the breadth of microfluidic cell sorting technologies, while focusing on those that offer the greatest potential for translation into clinical and industrial practice and that offer multiple, useful functions We organize these sorting technologies by the type of cell preparation required (ie, fluorescent label-based sorting, bead-based sorting, and label-free sorting) as well as by the physical principles underlying each sorting mechanism

Microfluidic cell sorting: a review of the advances in the separation of cells from debulking to rare cell isolation

When Segre and Silberberg in 1961 witnessed particles in a laminar pipe flow congregating at an annulus in the pipe, scientists were perplexed and spent decades learning why such behavior occurred, finally understanding that it was caused by previously unknown forces on particles in an inertial flow. The advent of microfluidics opened a new realm of possibilities for inertial focusing in the processing of biological fluids and cellular suspensions and created a field that is now rapidly expanding. Over the past five years, inertial focusing has enabled high-throughput, simple, and precise manipulation of bodily fluids for a myriad of applications in point-of-care and clinical diagnostics. This review describes the theoretical developments that have made the field of inertial focusing what it is today and presents the key applications that will make inertial focusing a mainstream technology in the future.

/pdf/inertial-focusing-in-microfluidics-5dlv4m3waa.pdf

Inertial Focusing in Microfluidics

Blood cell sorting is critical to sample preparation for both clinical diagnosis and therapeutic research. The spiral inertial microfluidic devices can achieve label-free, continuous separation of cell mixtures with high throughput and efficiency. The devices utilize hydrodynamic forces acting on cells within laminar flow, coupled with rotational Dean drag due to curvilinear microchannel geometry. Here, we report on optimized Archimedean spiral devices to achieve cell separation in less than 8 cm of downstream focusing length. These improved devices are small in size (<1 in.2), exhibit high separation efficiency (∼95%), and high throughput with rates up to 1 × 106 cells per minute. These device concepts offer a path towards possible development of a lab-on-chip for point-of-care blood analysis with high efficiency, low cost, and reduced analysis time.

Continuous separation of blood cells in spiral microfluidic devices

A wide range of microfluidic cell-sorting devices has emerged in recent years, based on both passive and active methods of separation. Curvilinear channel geometries are often used in these systems due to presence of secondary flows, which can provide high throughput and sorting efficiency. Most of these devices are designed on the assumption of two counter rotating Dean vortices present in the curved rectangular channels and existing in the state of steady rotation and amplitude. In this work, we investigate these secondary flows in low aspect ratio spiral rectangular microchannels and define their development with respect to the channel aspect ratio and Dean number. This work is the first to experimentally and numerically investigate Dean flows in microchannels for Re > 100, and show presence of secondary Dean vortices beyond a critical Dean number. We further demonstrate the impact of these multiple vortices on particle and cell focusing. Ultimately, this work offers new insights into secondary flow instabilities for low-aspect ratio, spiral microchannels, with improved flow models for design of more precise and efficient microfluidic devices for applications such as cell sorting and micromixing.

/pdf/dean-flow-dynamics-in-low-aspect-ratio-spiral-microchannels-2eip23cay7.pdf

Dean Flow Dynamics in Low-Aspect Ratio Spiral Microchannels.

Numerous applications in biology and medicine require the efficient and reliable separation of cells for disease diagnosis, genetic analysis, drug screening, and therapeutics. In this work, we demonstrate a novel technology that integrates a passive and an active device to separate, enrich and release cells on-demand from a complex blood sample, or cancer cells derived from a tissue biopsy. We exploit the high throughput (>1 mL min−1), size-based sorting capability of the passive spiral inertial microfluidic (iMF) device to focus particles/cells towards an active lateral cavity acoustic transducer (LCAT) device for size-selective enrichment. We demonstrate that this platform is capable of efficiently (>90%) removing smaller cells, such as RBCs in a blood sample or smaller cancer cells in a heterogeneous cell line, and providing 44 000× enrichment from the remaining sample within 5 min of device operation. Finally, we use this platform for two applications: selective enrichment of the side-population of DU-145 cells from tissue biopsy and isolation of larger monocytes from blood. Our platform integrates the high throughput (processing rate) capacity of spiral iMF with the high selectivity of LCAT, thereby offering a unique route for highly-selective, label-free particle/cell sorting, with potential application in lab-on-chip platforms for liquid biopsy and diagnostics applications.

A high throughput microfluidic platform for size-selective enrichment of cell populations in tissue and blood samples.

Spiral inertial microfluidic channels have been used for cell sorting with high efficiency and throughput, based on the assumption of two counter-rotating Dean vortices in the channel cross-section. However, this assumption does not explain the shift in focusing of the cells or particles upon increase in the flow rate. In this work, for the first time we show presence of a secondary set of Dean vortices in spiral microchannels. This observation redefines the way Dean flows are used for cell focusing at higher flow rates, potentially leading to higher efficiency separations at ultra-high throughputs.

/pdf/evolution-of-secondary-dean-vortices-in-spiral-microchannels-4tes4hmgy7.pdf

Evolution of secondary dean vortices in spiral microchannels for cell separations

In this work, we demonstrate continuous size-based sorting and separation of cells in a simple passive microfluidic device. Our approach takes advantage of the principles of inertial microfluidics and Dean drag forces in spiral microchannels for successful separation of HPET (human prostate epithelial) cells, obtained from a high grade (Gleason 9) prostate punch biopsy, with high throughput (~10,000cells/min) and separation efficiency (>90%). The approach can be extended to other cell types and mixtures.

/pdf/sorting-human-prostate-epithelial-hpet-cells-in-an-inertial-1ul6mbf005.pdf

Nivedita Nivedita

Papers

Continuous separation of blood cells in spiral microfluidic devices

Dean Flow Dynamics in Low-Aspect Ratio Spiral Microchannels.

A high throughput microfluidic platform for size-selective enrichment of cell populations in tissue and blood samples.

Evolution of secondary dean vortices in spiral microchannels for cell separations

Sorting human prostate epithelial (hpet) cells in an inertial microfluidic device