We have demonstrated label free detection of CD4+ and CD8+ T-Lymphocyte whole cells and CD4+ T-Lymphocyte cell lysis using the optofluidic ring resonator (OFRR) sensor. The OFRR sensing platform incorporates microfluidics and photonics in a setup that utilizes small sample volume and achieves a fast detection time. In this work, white blood cells were isolated from healthy blood and the concentrations were adjusted to match T-Lymphocyte levels of individuals infected with HIV. Detection was accomplished by immobilizing CD4 and CD8 antibodies on the inner surface of the OFRR. Sensing results show excellent detection of CD4+ and CD8+ T-Lymphocyte cells at medically significant concentrations with a detection time of approximately 30 minutes. This work will lead to a rapid and low-cost sensing device that can provide a CD4 and CD8 count as a measure of HIV progression.
References
[1]
Sia, S.K.; Chin, C.D.; Linder, V. Lab-on-a-chip Devices for Global Health: Past Studies and Future Opportunities. Lab Chip?2006, 7, 41–57.
[2]
Gemignani, M.; Maiman, M.; Fruchter, R.G.; Arrastia, C.D.; Gibbon, D.; Ellison, T. CD4 Lymphocytes in Women with Invasive and Preinvasive Cervical Neoplasia. Gynecol. Oncol?1995, 59, 364–369.
[3]
Cheng, X.; Irimia, D.; Dixon, M.; Sekine, K.; Demirci, U.; Zamir, L.; Tompkins, R.G.; Rodriguez, W.; Toner, M. A Microfluidic Device for Practical Label-free CD4+ T Cell Counting of HIV-infected Subjects. Lab Chip?2006, 7, 170–178.
[4]
Autran, B.; Carcelain, G.; Li, T.S.; Blanc, C.; Mathez, D.; Tubiana, R.; Katlama, C.; Debre, P.; Leibowitch, J. Positive Effects of Combined Antiretroviral Therapy on CD4+ T Cell Homeostasis and Function in Advanced HIV Disease. Science?1997, 277, 112–116.
[5]
Kaufmann, D.; Pantaleo, G.; Sudre, P.; Telenti, A. CD4-Cell Count in HIV-1 Infected Individuals Remaining Viraemic with Highly Active Antiretroviral Therapy (HAART). Lancet?1998, 351, 723–728.
[6]
Gazzard, B.; Committee, B.W. British HIV Association (BHIVA) Guidelines for the Treatment of HIV-infected Adults with Antiretroviral Therapy. HIV Med?2006, 7, 487–503.
[7]
DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-infected Adults and Adolescents, Available online: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf (accessed on 1 December 2009).
[8]
Phillips, A.N.; Sabin, C.A.; Elford, J.; Bofill, M.; Lee, C.A.; Janossy, G. CD8 Lymphocyte Counts and Serum Immunoglobulin a Levels Early in HIV Infection as Predictors of CD4 Lymphocyte Depletion During 8 Years of Follow-up. AIDS?1993, 7, 975–980.
[9]
Taylor, J.M.; Fahey, J.L.; Detels, R.; Giorgi, J.V. CD4 Percentage, CD4 Number, and CD4:CD8 Ratio in HIV Infection: Which to Choose and How to Use. J. AIDS?1989, 2, 114–124.
[10]
Rabin, R.L.; Roederer, M.; Maldonado, Y.; Petru, A.; Herzenberg, L.A.; Herzenberg, L.A. Altered Representation of Naive and Memory CD8 T Cell Subsets in HIV-infected Children. J. Clin. Invest?1995, 95, 2054–2060.
[11]
Roederer, M.; Dubs, J.G.; Anderson, M.T.; Raju, P.A.; Herzenberg, L.A.; Herzenberg, L.A. CD8 Naive T Cell Counts Decrease Progressively in HIV-infected Adults. J. Clin. Invest?1995, 95, 2061–2066.
[12]
Livingstone, W.J.; Moore, M.; Innes, D.; Bell, J.E.; Simmonds, P.; Study, E.H.T. Frequent Infection of Peripheral Blood CD8-Positive T-Lymphocytes with HIV-1. Lancet?1996, 348, 649–654.
[13]
Strauss, K.; Hannet, I.; Engels, S.; Shiba, A.; Ward, D.M.; Ullery, S.; Jinguji, M.G.; Valinsky, J.; Barnett, D.; Orfao, A.; Kestens, L. Performance Evaluation of the FACSCount System: A Dedicated System for Clinical Cellular Analysis. Cytometry?1996, 26, 52–59.
[14]
Jokerst, J.V.; Floriano, P.N.; Christodoulides, N.; Simmons, G.W.; McDevitt, J.T. Integration of Semiconductor Quantum Dots into Nano-bio-chip Systems for Enumeration of CD4+ T Cell Counts as the Point-of-need. Lab Chip?2008, 8, 2080–2090.
[15]
Wang, Y.; Kang, Y.; Xu, D.; Chon, C.H.; Barnett, L.; Kalams, S.A.; Li, D.; Li, D. On-Chip Counting the Number and Percentage of CD4+ T-Lymphocytes. Lab Chip?2007, 8, 309–315.
Zhu, H.; White, I.M.; Suter, J.D.; Dale, P.S.; Fan, X. Analysis of Biomolecule Detection with Optofluidic Ring Resonator Sensors. Opt. Express?2007, 15, 9139–9146.
[20]
Suter, J.D.; White, I.M.; Zhu, H.; Shi, H.; Caldwell, C.W.; Fan, X. Label-Free Quantitative DNA Detection Using the Liquid Core Optical Ring Resonator. Biosens. Bioelectron?2007, 23, 1003–1009.
[21]
Yang, G.; White, I.M.; Fan, X. An Opto-fluidic Ring Resonator Biosensor for the Detection of Organophosphorus Pesticides. Sens. Actuator. B Chem?2008, 133, 105–112.
[22]
White, I.; Gohring, J.; Fan, X. SERS-Based Detection in an Optofluidic Ring Resonator Platform. Opt. Express?2007, 15, 17433–17442.