Effect of Biointerfacing Linker Chemistries on the Sensitivity of Silicon Nanowires for Protein Detection

Point-of-care diagnostics show promise in removing reliance on centralized lab testing facilities and may help increase both the survival rate for infectious diseases as well as monitoring of chronic illnesses. CMOS compatible diagnostic platforms are currently being considered as possible solutions as they can be easily miniaturized and can be cost-effective. Top-down fabricated silicon nanowires are a CMOS-compatible technology which have demonstrated high sensitivities in detecting biological analytes, such as proteins, DNA, and RNA. However, the reported response of nanowires to these analytes has varied widely since several different functionalization protocols have been attempted with little characterization and comparison. Here we report protocols for fabrication and functionalization of silicon nanowires which yield highly stable nanowires in aqueous solutions and limits of detection to ∼1 pg/mL of the model protein used in the study. A thorough characterization was done into optimizing the release of the silicon nanowires using combined dry and wet etch techniques, which yielded nanowires that could be directly compared to increase output statistics. Moreover, a range of different linker chemistries were tried for reacting the primary antibody, and its response to target and nonspecific antigens, with polyethylene glycol based linker BS­(PEG)₅ providing the best response. Consequently, this chemistry was used to characterize different oxide thicknesses and their responses to the mouse IgG antigen, which with the smallest oxide thickness yielded 0.1–1 pg/mL limits of detection and a dynamic range over 3 orders of magnitude

(a)cells exhibit negative DEP at 1 kHz and 3 Vpp; they are collected at the centers of the finger electrodes

(b) Some of the cells exhibit negative DEP, while others exhibit positive DEP, at 10 kHz and 3 Vpp; Cells are collected at both the centers of the finger electrodes and the edges of the finger electrodes. (c) As frequency increases to 50 kHz (at 3 Vpp), all the cells exhibit positive DEP and are collected at the edges of the finger electrodes.<p><b>Copyright information:</b></p><p>Taken from "Effects of Dielectrophoresis on Growth, Viability and Immuno-reactivity of "</p><p>http://www.jbioleng.org/content/2/1/6</p><p>Journal of Biological Engineering 2008;2():6-6.</p><p>Published online 16 Apr 2008</p><p>PMCID:PMC2373775.</p><p></p

The ELISA results for the immuno-reactivity of DEP treated and untreated cells to PAb Lm404 (anti-InlB), PAb C639 (anti-ActA), anti-species antibody from KPL (Gathersburg, MD) and C11E9 monoclonal antibody

Cell concentrations were about 10cfu/ml. Statistically significant difference was observed at P > 0.0002 (*) and P > 0.009 (**).<p><b>Copyright information:</b></p><p>Taken from "Effects of Dielectrophoresis on Growth, Viability and Immuno-reactivity of "</p><p>http://www.jbioleng.org/content/2/1/6</p><p>Journal of Biological Engineering 2008;2():6-6.</p><p>Published online 16 Apr 2008</p><p>PMCID:PMC2373775.</p><p></p

The growth profiles of DEP-treated in LCGM medium monitored by real time pH measurements, along with control samples

The DEP treatment conditions and initial cell numbers in the samples are shown in each plot. DEP voltages for all samples were at 20 Vpp. Arrows indicate the detection times on pH-growth curves.<p><b>Copyright information:</b></p><p>Taken from "Effects of Dielectrophoresis on Growth, Viability and Immuno-reactivity of "</p><p>http://www.jbioleng.org/content/2/1/6</p><p>Journal of Biological Engineering 2008;2():6-6.</p><p>Published online 16 Apr 2008</p><p>PMCID:PMC2373775.</p><p></p

Additional file 3: Table S3. of Design and integration of a problem-based biofabrication course into an undergraduate biomedical engineering curriculum

Responses to Rating Scale Questions in Mid- and End-Course Surveys. (DOC 29 kb

Additional file 5: Table S5. of Design and integration of a problem-based biofabrication course into an undergraduate biomedical engineering curriculum

Responses to Open-Ended Questions in Mid-Course Survey. (DOC 31 kb

Additional file 1: Table S1. of Design and integration of a problem-based biofabrication course into an undergraduate biomedical engineering curriculum

Detailed Course Schedule. (DOC 145 kb

Additional file 4: Table S4. of Design and integration of a problem-based biofabrication course into an undergraduate biomedical engineering curriculum

Responses to Rating Scale Questions in End-Course Survey. (DOC 30 kb

Additional file 2: Table S2. of Design and integration of a problem-based biofabrication course into an undergraduate biomedical engineering curriculum

Lab Supply Inventory. (DOC 45 kb

Real-time SLIM setup.

<p>The inset I shows the coherent summation of the scattered and unscattered lights. The inset II shows the SLIM image of a micro-bead (3.0 µm diameter) immersed in oil. The measured height is 3.04 µm.</p