Researchers at the Stanford University School of Medicine have developed a way to produce a cheap and reusable diagnostic "lab-on-a-chip" with the help of an ordinary inkjet printer - at a production cost of as little as US$ 0.01 per chip. Ron Davis, PhD, professor of biochemistry and of genetics and director of the Stanford Genome Technology Center believes this new technology could usher in a medical diagnostics revolution like the kind brought on by low-cost genome sequencing.
The inexpensive lab-on-a-chip technology has the potential to enhance diagnostic capabilities around the world, especially in developing countries. Due to inferior access to early diagnostics, the survival rate of breast cancer patients is only 40% in low-income nations — half the rate of such patients in developed nations. Other life-threatening diseases, such as malaria, tuberculosis and HIV, also have high incidence and bad patient outcomes in developing countries.
Better access to cheap diagnostics could help turn this around, especially as most such equipment costs thousands of dollars.
A combination of microfluidics, electronics and inkjet printing technology, the lab-on-a-chip is a two-part system. The first is a clear silicone microfluidic chamber for housing cells and a reusable electronic strip. The second part is a regular inkjet printer that can be used to print the electronic strip onto a flexible sheet of polyester using commercially available conductive nanoparticle ink.
Figure: Stanford University - The lab on a chip comprises a clear silicone microfluidic chamber for housing cells and a reusable electronic strip — a flexible sheet of polyester with commercially available conductive nanoparticle ink
Designed as a multifunctional platform, one of its applications is that it allows users to analyse different cell types without using fluorescent or magnetic labels that are typically required to track cells. Instead, the chip separates cells based on their intrinsic electrical properties: When an electric potential is applied across the inkjet-printed strip, cells loaded into the microfluidic chamber get pulled in different directions depending on their "polarizability" in a process called dielectrophoresis. This label-free method to analyse cells greatly improves precision and cuts lengthy labelling processes.
The tool is designed to handle small-volume samples for a variety of assays. The researchers showed the device can help capture single cells from a mix, isolate rare cells and count cells based on cell types. The cost of these multifunctional biochips is orders of magnitude lower than that of the individual technologies that perform each of those functions. A standalone flow cytometer machine, for example, which is used to sort and count cells, costs US$100,000, without taking any operational costs into account.
According to the researchers the technology has the potential to not only advance health care, but also to accelerate basic and applied research. It would allow scientists and clinicians to potentially analyse more cells in shorter time periods, manipulate stem cells to achieve efficient gene transfer and develop cost-effective ways to diagnose diseases.
The team hopes the chip will create a transformation in how people use instruments in the lab.
The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.
The research was supported by a grant from the National Institutes of Health (grant HG000205). The departments of Biochemistry and of Genetics also supported the work.
Rahim Esfandyarpour, PhD, an engineering research associate at the genome center, "Enabling early detection of diseases is one of the greatest opportunities we have for developing effective treatments." Rahim added, "Maybe $1 in the U.S. doesn’t count that much, but somewhere in the developing world, it’s a lot of money."
Rahim continued, "We designed it to eliminate the need for clean-room facilities and trained personnel to fabricate such a device. One chip can be produced in about 20 minutes."
Ron Davis, PhD, professor of biochemistry and of genetics and director of the Stanford Genome Technology Center, said, "The low cost of the chips could democratise diagnostics similar to how low-cost sequencing created a revolution in health care and personalised medicine." Ron added, "Inexpensive sequencing technology allows clinicians to sequence tumour DNA to identify specific mutations and recommend personalised treatment plans. In the same way, the lab on a chip has the potential to diagnose cancer early by detecting tumour cells that circulate in the bloodstream."
Multifunctional, inexpensive, and reusable nanoparticle-printed biochip for cell manipulation and diagnosis
Rahim Esfandyarpour | Matthew J. DiDonatoc | Yuxin Yang | Naside Gozde Durmus | James S. Harris | Ronald W. Davis
Point-of-care diagnostics in the developing world and resource-limited areas require numerous special design considerations to provide effective early detection of disease. Of particular need for these contexts are diagnostic technologies featuring low costs, ease of use, and broad applicability. Here we present a nanoparticle-inkjet-printable microfluidics-based platform that fulfills these criteria and that we expect to significantly reduce the footprint, complexity, and cost of clinical diagnostics. This reusable $0.01 platform is miniaturized to handle small sample volumes and can perform numerous analyses. It can perform complex, minimally invasive analyses of single cells without specialized equipment and personnel. This inexpensive, accessible platform has broad applications in precision diagnostics and is a step toward the democratization of medical technologies.
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-on-a-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, time-consuming, 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.