Multifunctional, inexpensive, and reusable nanoparticle-printed biochip for cell manipulation and diagnosis

Abstract

Isolation and characterization of rare cells and molecules from a heterogeneous population is of critical importance in diagnosis of common lethal diseases such as malaria, tuberculosis, HIV, and cancer. For the developing world, point-of-care (POC) diagnostics design must account for limited funds, modest public health infrastructure, and low power availability. To address these challenges, here we integrate microfluidics, electronics, and inkjet printing to build an ultra-low-cost, rapid, and miniaturized lab-ona-chip (LOC) platform. This platform can perform label-free and rapid single-cell capture, efficient cellular manipulation, rare-cell isolation, selective analytical separation of biological species, sorting, concentration, positioning, enumeration, and characterization. The miniaturized format allows for small sample and reagent volumes. By keeping the electronics separate from microfluidic chips, the former can be reused and device lifetime is extended. Perhaps most notably, the device manufacturing is significantly less expensive, timeconsuming, and complex than traditional LOC platforms, requiring only an inkjet printer rather than skilled personnel and clean-room facilities. Production only takes 20 min (vs. up to weeks) and $0.01-an unprecedented cost in clinical diagnostics. The platform works based on intrinsic physical characteristics of biomolecules (e.g., size and polarizability). We demonstrate biomedical applications and verify cell viability in our platform, whose multiplexing and integration of numerous steps and external analyses enhance its application in the clinic, including by nonspecialists. Through its massive cost reduction and usability we anticipate that our platform will enable greater access to diagnostic facilities in developed countries as well as POC diagnostics in resource-poor and developing countries.lab on a chip | point of care | diagnostics | nanoparticles | microfluidics

Patterning of Nanoparticle‐Based Aerogels and Xerogels by Inkjet Printing

“…In contrast to conventional techniques (dip‐coating, spin‐coating, spray‐coating) the inkjet printing process exhibits benefits of faster manufacturability, a lower material to sample casualty rate, and the production of defined areas with less coating material. Plenty of scientists are using inkjet printing for the deposition of metal NCs or semiconductor NCs to manufacture structured electronic components for chip design and sensing . In addition, some works on laser induced 3D printing for the fabrication of porous materials can be found .…”

Electrical measurement of cross-sectional position of particles flowing through a microchannel

“…In particular, microfluidic impedance cytometers for label-free analysis of single particles and cells at high throughput (Cheung et al 2010;Sun and Morgan 2010;Petchakup et al 2017) have been used in different biological assays, including particle sizing and counting, cell phenotyping and disease diagnostics [e.g. Haandbaek et al (2016), McGrath et al (2017), Rohani et al (2017), Esfandyarpour et al (2017) and Rollo et al (2017)]. Those systems use electrodes integrated in a microchannel to measure variation in the electric field caused by the transit of particles.…”

Lab-on-a-Chip Technologies for the Single Cell Level: Separation, Analysis, and Diagnostics

“…In recent years, more and more targets for detection on diagnostic chips have been investigated. Some salient examples thereof are circulating tumor cells (CTC) of various types of cancer [1,[36][37][38], rare cells (e.g., sickle-cell variants of red blood cells) [39,40], parasites, like Plasmodium falciparum [1,7,10,11,[13][14][15][21][22][23]36,[41][42][43][44][45][46][47][48][49][50] and Trypanosoma spp. [8,44,[51][52][53][54][55][56][57] and even plant pathogens [26,58], as well as-after cells have been lysed-subcellular infection markers (e.g., DNA, RNA fragments) [10,11,22,43,[59][60][61][62].…”

“…This is often achieved with the LAMP test and its derivatives, LAMPport and NINA-LAMP [22,47,48,55,61]. However, many other, especially microfluidic, approaches have also been tested and discussed for their aptitude to be used for POC diagnostic tools [38,45,205,212,[221][222][223][224][225].…”