Microfluidics and photonics for Bio-System-on-a-Chip: A review of advancements in technology towards a microfluidic flow cytometry chip

Autor: Frank S. Tsai, Chun-Hao Chen, Yu-Hwa Lo, Jessica Godin, Sung Hwan Cho, Wen Qiao
Rok vydání: 2008
Předmět:
Zdroj: Journal of Biophotonics. 1:355-376
ISSN: 1864-0648
1864-063X
DOI: 10.1002/jbio.200810018
Popis: Microfluidics and photonics come together to form a field commonly referred to as ‘optofluidics’. Flow cytometry provides the field with a technology base from which both microfluidic and photonic components be developed and integrated into a useful device. This article reviews some of the more recent developments to familiarize a reader with the current state of the technologies and also highlights the requirements of the device and how researchers are working to meet these needs. A microfluidic flow cytometer protoype employing on-chip lenses for illumination and light collection in conjunction with a microfluidic sample flow system for device miniaturization. Keywords: Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS), cells on a chip, other integrated-optical elements and systems, fabrication techniques, lithography, pattern transfer, flows in microelectromechanical systems (MEMS) and nanoelectromechanical systems (NEMS), fluorescence 1. Introduction Over the past decade, the field of microfluidics has begun to show great promise for research assays and diagnostics as well as for clinical applications. The field has evolved from devices comprised of simple microfluidic channels into complex devices that can mix fluids [1], pump liquids [2], perform digital logic [3–6], individually culture cells [7], determine optimal reaction conditions [8], and much more. Small-scale fluidic devices, by definition, will have a low Reynolds number, making controlled laminar flow systems easily achievable. Microfluidics further offers the advantages of small size for miniaturization and parallelization of devices. Furthermore, this small size opens the door to the potential of portable devices. Additionally, typical fabrication processes often readily lend themselves to mass production, potentially helping to create lower-cost devices. With these advantages, the idea of low-cost lab-on-a-chip devices can start to become a reality [9]. Such devices would be very useful to researchers, clinical laboratories, and point-of-care clinicians in remote and/or resource-poor settings. The functionality of microfluidics will expand greatly if these devices can be combined with photonics to create a new technology platform: integrated microfluidic photonics, often referred to as optofluidics [10]. Embracing photonics is a logical path of evolution for microfluidics, as the most popular techniques for biological and chemical detection are photonic in nature. Fluorescence, fluorescence resonance energy transfer (FRET), optical scattering, and surface-enhanced Raman spectroscopy (SERS) are some the most effective and accurate methods to detect analytes at the cellular and molecular level. Integration of microfluidics with photonics represents not only a new technology platform but also a transformation to the new paradigm of bio-system-on-a-chip (BSoC) [11]. As electronic integrated circuits have transformed the world of electronics, integrated microfluidic photonic circuits hold the promise to revolutionize the field of biomedicine. In spite of the rapid advances in microfluidics and photonics, however, the field is admittedly still in its embryonic stage. Technological innovations and breakthroughs are needed to demonstrate the performance and cost advantages offered through miniaturization and integration. Given the diversity of the applications, target application is needed to guide the technology development; a bio-system that is not only the workhorse for the industry but also a test vehicle to assess and benchmark the technology. The flow cytometer, or FACS (fluorescence-activated cell sorter), is just the candidate to meet these requirements. Flow cytometers are commonly-used research and clinical tool in which the properties of each component of a sample, such as cells, are individually measured. A flow system brings cells one by one past an interrogation point, where they are illuminated by a light source. Typically the system is comprised of fluid flow through a small laser beam. As each analyte is illuminated, it scatters light with a characteristic directional intensity distribution. Further, fluorescently tagged antibodies are often used to mark and identify cells (immunofluorescence). Fluorescence may also be measured when stains are used (to quantify DNA content, show cell viability, etc), or when fluorescent proteins are present (for example when used as reporters in research settings). Thus light scattered from the cell and one or more colors of fluorescence emitted from the illuminated cell are measured, providing a number of parameters to yield statistics about the samples subpopulations. In addition, many machines have a sorting apparatus to isolate analytes of interest for further study. The development of new cytometers is typically focused on either enhancing performance (higher throughput, more measurable parameters) or increasing accessibility (smaller, less expensive machines). The cytometer is almost inherently microfluidic in nature, rapidly interrogating small volumes of fluid. Taking the cytometer to a microfluidic platform could transform the device into a smaller, possibly mass-producible machine, and may be able to address performance enhancement as well. The cost of the cytometer, currently around $30,000 for more basic research models and more typically on the order of $100,000, could be significantly lowered, opening up new markets that were previously inaccessible due to prohibitive costs. Additionally, microfluidic cartridges could potentially be disposable, supplying a sterile device as well as containing and limiting exposure to biohazardous materials such as blood. Disposable devices also bypass the issue of device clogging, a problem experienced in benchtop cytometry, by allowing the user to quickly replace the microfluidic cartridge and continue their work. Microfluidic devices may further be able to reduce the sample size necessary for some assays, such as T-cell enumeration for HIV patients, limiting the amount of blood needed from patients as well as reducing the necessary volume of costly reagents, helping to lower testing costs. As with any new technology platform, though, there are a number of obstacles that must be overcome to realize a practical microfluidic flow cytometer. Recent research has made great headway on a number of fronts. This article takes a look at recent progress towards the achievement of a lab-on-a-chip flow cytometer. The basic cytometer includes (i) a fluidic system, (ii) an optical interrogation system and systems for light collection, and often (iii) a cell sorting apparatus. Advances pertaining to each of these components will be discussed.
Databáze: OpenAIRE
Externí odkaz: