Abstract
As the point of care diagnosis devices are becoming ever more popular, this paper suggest a miniaturized testing device from a drop of blood to diagnosis of disease for the global healthcare. The minimal requirements for the POC blood-testing device are blood microsampling, blood separation, immunoassay, and detection and communication of the signals. The microsampling of the blood can be achieved by specialized needle, which can be connected to the microchip or analytical devices. The sampled blood is then separated using either a filter (weir or pillar type), or by the phenomena unique to microfluidic system. The separated blood should then go through sandwich, homogeneous non-competitive, or competitive immunoassay, which can effectively diagnose diverse diseases. Lastly, the device should detect and translate the immune-signals to readable, and clinically significant signals. The development of such device will play a great role for improving healthcare technology.
Article PDF
Similar content being viewed by others
References
Sorger PK. Microfluidics closes in on point-of-care assays. Nat Biotechnol. 2008; 26(12):1345–1346.
Webb SA. Returning to diagnostic basics. BioTechniques. 2010; 49(1):491–493.
Grayson AR, Shawgo RS, Johnson AM, Flynn NT, Li Y, Cima MJ, Langer R. A BioMEMS review: MEMS technology for physiologically integrated devices. Proc IEEE. 2004; 92(1):6–21.
Jeong GS, Chung S, Kim CB, Lee SH. Applications of micromixing technology. Analyst. 2010; 135(3):460–473.
Ng J, Shin Y, Chung S. Microfluidic platforms for the study of cancer metastasis. Biomed Eng Lett. 2012; 2(2):72–77.
Park JY, Takayama S, Lee SH. Regulating microenvironmental stimuli for stem cells and cancer cells using microsystems. Integrative Biol. 2010; 2(5–6):229–240.
Quake SR, Scherer A. From micro-to nanofabrication with soft materials. Sci. 2000; 290(5496):1536–1540.
Whitesides GM, Ostuni E, Takayama S, Jiang X, Ingber DE. Soft lithography in biology and biochemistry. Annu Rev Biomed Eng. 2001; 3(1):335–373.
Li T, Barnett A, Rogers KL, Gianchandani YB. A blood sampling microsystem for pharmacokinetic applications: design, fabrication, and initial results. Lab Chip. 2009; 9(24):3495–3503.
Kim MT, Son J, Cho CN, Park CM, Kim KG. Quantitative analysis of applied force on biopsy needle insertions. Biomed Eng Lett. 2012; 2(4):249–254.
Aoyagi S, Izumi H, Isono Y, Makihira K, Fukuda M. Biodegradable polymer needle having a trench for collecting blood by capillary force. Micro electro mechanical systems. Int Conf IEEE MEMS. 2006. 1:450–453.
Mukerjee E, Collins S, Isseroff R, Smith R. Microneedle array for transdermal biological fluid extraction and in situ analysis. Sensor Actuat A-Phys. 2004; 114(2):267–275.
Beebe DJ, Mensing GA, Walker GM. Physics and applications of microfluidics in biology. Annu Rev Biomed Eng. 2002; 4(1):261–286.
Kim ES, Kim S, Choi KY, Han KH. Micro-/nanotechnologybased isolation and clinical significance of circulating tumor cells. Biomed Eng Lett. 2012; 2(2):78–87.
VanDelinder V, Groisman A. Separation of plasma from whole human blood in a continuous cross-flow in a molded microfluidic device. Anal Chem. 2006; 78(11):3765–3771.
Moorthy J, Beebe DJ. In situ fabricated porous filters for microsystems. Lab Chip. 2003; 3(2):62–66.
Crowley TA, Pizziconi V. Isolation of plasma from whole blood using planar microfilters for lab-on-a-chip applications. Lab Chip. 2005; 5(9):922–929.
Chen X, Cui DF, Liu CC, Li H. Microfluidic chip for blood cell separation and collection based on crossflow filtration. Sensor Actuat B-Chem. 2008; 130(1):216–221.
Doyeux V, Podgorski T, Peponas S, Ismail M, Coupier G. Spheres in the vicinity of a bifurcation: elucidating the Zweifach-Fung effect. J Fluid Mech. 2011; 674:359.
Yang S, Ündar A, Zahn JD. A microfluidic device for continuous, real time blood plasma separation. Lab Chip. 2006; 6(7):871–880.
Choi S, Song S, Choi C, Park JK. Continuous blood cell separation by hydrophoretic filtration. Lab Chip. 2007; 7(11):1532–1538.
Lee S, Lee S. Micro total analysis system (µ-TAS) in biotechnology. Appl Microbiol Biot. 2004; 64(3):289–299.
Wild DG. The immunoassay handbook: theory and applications of ligand binding, ELISA and related techniques. Sci. 2013.
Wehmeyer KR, Halsall H, Heineman W. Heterogeneous enzyme immunoassay with electrochemical detection: competitive and “sandwich”-type immunoassays. Clin Chem. 1985; 31(9):1546–1549.
Beck M, Brockhuis S, van der Velde N, Breukers C, Greve J, Terstappen LW. On-chip sample preparation by controlled release of antibodies for simple CD4 counting. Lab Chip. 2012; 12(1):167–173.
Darain F, Gan KL, Tjin SC. Antibody immobilization on to polystyrene substrate-on-chip immunoassay for horse IgG based on fluorescence. Biomed Microdevices. 2009; 11(3):653–661.
Ko YJ, Maeng JH, Ahn Y, Hwang SY, Cho NG, Lee SH. Microchip based multiplex electro immunosensing system for the detection of cancer biomarkers. Electrophoresis. 2008; 29(16):3466–3476.
Lin CC, Wang JH, Wu HW, Lee GB. Microfluidic immunoassays. J Lab Autom. 2010; 15(3):253–274.
Meagher RJ, Hatch AV, Renzi RF, Singh AK. An integrated microfluidic platform for sensitive and rapid detection of biological toxins. Lab Chip. 2008; 8(12):2046–2053.
Reichmuth DS, Wang SK, Barrett LM, Throckmorton DJ, Einfeld W, Singh AK. Rapid microchip-based electrophoretic immunoassays for the detection of swine influenza virus. Lab Chip. 2008; 8(8):1319–1324.
Yoo SJ, Choi YB, Ju JI, Tae GS, Kim HH, Lee SH. Microfluidic chip-based electrochemical immunoassay for hippuric acid. Analyst. 2009; 134(12):2462–2467.
Hu M, Yan J, He Y, Lu H, Weng L, Song S, Fan C, Wang L. Ultrasensitive, multiplexed detection of cancer biomarkers directly in serum by using a quantum dot-based microfluidic protein chip. Acs Nano. 2009; 4(1):488–494.
Bhattacharyya A, Klapperich C. Design and testing of a disposable microfluidic chemiluminescent immunoassay for disease biomarkers in human serum samples. Biomed Microdevices. 2007; 9(2):245–251.
Yu L, Li CM, Liu Y, Gao J, Wang W, Gan Y. Flow-through functionalized PDMS microfluidic channels with dextran derivative for ELISAs. Lab Chip. 2009; 9(9):1243–1247.
Kurita R, Yokota Y, Sato Y, Mizutani F, Niwa O. On-chip enzyme immunoassay of a cardiac marker using a microfluidic device combined with a portable surface plasmon resonance system. Anal Chem. 2006; 78(15):5525–5531.
Chon H, Lim C, Ha SM, Ahn Y, Lee EK, Chang SI, Seong GH, Choo J. On-chip immunoassay using surface-enhanced Raman scattering of hollow gold nanospheres. Anal Chem. 2010; 82(12):5290–5295.
Guan JG, Miao YQ, Chen JR. Prussian blue modified amperometric FIA biosensor: one-step immunoassay for — fetoprotein. Biosens Bioelectron. 2004; 19(8):789–794.
Rossier JS, Girault HH. Enzyme linked immunosorbent assay on a microchip with electrochemical detection. Lab Chip. 2001; 1(2):153–157.
Jang Y, Oh SY, Park JK. In situ electrochemical enzyme immunoassay on a microchip with surface-functionalized poly (dimethylsiloxane) channel. Enzyme Microb Tech. 2006; 39(5):1122–1127.
Zhao WW, Ma ZY, Yu PP, Dong XY, Xu JJ, Chen HY. Highly sensitive photoelectrochemical immunoassay with enhanced amplification using horseradish peroxidase induced biocatalytic precipitation on a CdS quantum dots multilayer electrode. Anal Chem. 2011; 84(2):917–923.
Backmann N, Zahnd C, Huber F, Bietsch A, Plückthun A, Lang HP, Güntherodt HJ, Hegner M, Gerber C. A label-free immunosensor array using single-chain antibody fragments. Proc Natl Acad Sci USA. 2005; 102(41):14587–14592.
Hwang KS, Lee JH, Yoon DS, Park JH, Kim TS. In-situ quantitative analysis of a prostate-specific antigen (PSA) using a nanomechanical PZT cantilever. Lab Chip. 2004; 4(6):547–552.
Gubala V, Harris LF, A. Ricco J, Tan MX, Williams DE. Point of care diagnostics: status and future. Anal Chem. 2012; 84(2):487.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lee, J., Lee, SH. Lab on a chip for in situ diagnosis: From blood to point of care. Biomed. Eng. Lett. 3, 59–66 (2013). https://doi.org/10.1007/s13534-013-0094-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13534-013-0094-y