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E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum.

ABSTRACT: The multiplexed, point-of-care measurement of specific antibodies could improve the speed with which diseases are diagnosed and their treatment initiated. To this end, we are developing E-DNA scaffold sensors, which consist of a rigid, nucleic acid "scaffold" attached on one end to an electrode and presenting both a redox reporter and an epitope on the other. In the absence of antibody, the reporter efficiently transfers electrons when interrogated electrochemically. Binding-induced steric hindrance limits movement, reducing electron transfer in a manner that is both easily measured and quantitatively related to target concentration. Previously we have used monoclonal antibodies to explore the analytical performance of E-DNA sensors, showing that they support the rapid, single-step, quantitative detection of multiple antibodies in small volume samples. Here, in contrast, we employ authentic human samples to better explore the platform's clinical potential. Specifically, we developed E-DNA sensors targeting three HIV-specific antibodies and then compared the analytical and clinical performance of these against those of gold standard serological techniques. Doing so we find that, although the multistep amplification of an ELISA leads to a lower detection limits, the clinical sensitivity of ELISAs, E-DNA sensors and lateral-flow dipsticks are indistinguishable across our test set. It thus appears that, by merging the quantitation and multiplexing of ELISAs with the convenience and speed of dipsticks, E-DNA scaffold sensors could significantly improve on current serological practice.

SUBMITTER: Parolo C

PROVIDER: S-EPMC8433188 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Gait impairments including shuffling gait and hesitation are common in people with Parkinson's disease (PD), and have been linked to increased fall risk and freezing of gait. Nowadays the gait metrics mostly focus on the spatiotemporal characteristics of gait, but less is known of the angular characteristics of the gait, which may provide helpful information pertaining to the functional status and effects of the treatment in PD. OBJECTIVE:This study aimed to quantify the angles of steps during walking, and explore if this novel step angle metric is associated with the severity of PD and the effects of the treatment including the acute levodopa challenge test (ALCT) and deep brain stimulation (DBS). METHODS:A total of 18 participants with PD completed the walking test before and after the ALCT, and 25 participants with PD completed the test with the DBS on and off. The walking test was implemented under two conditions: walking normally at a preferred speed (single task) and walking while performing a cognitive serial subtraction task (dual task). A total of 17 age-matched participants without PD also completed this walking test. The angular velocity was measured using wearable sensors on each ankle, and three gait angular metrics were obtained, that is mean step angle, initial step angle, and last step angle. The conventional gait metrics (ie, step time and step number) were also calculated. RESULTS:The results showed that compared to the control, the following three step angle metrics were significantly smaller in those with PD: mean step angle (F1,48=69.75, P<.001, partial eta-square=0.59), initial step angle (F1,48=15.56, P<.001, partial eta-square=0.25), and last step angle (F1,48=61.99, P<.001, partial eta-square=0.56). Within the PD cohort, both the ALCT and DBS induced greater mean step angles (ACLT: F1,38=5.77, P=.02, partial eta-square=0.13; DBS: F1,52=8.53, P=.005, partial eta-square=0.14) and last step angles (ACLT: F1,38=10, P=.003, partial eta-square=0.21; DBS: F1,52=4.96, P=.003, partial eta-square=0.09), but no significant changes were observed in step time and number after the treatments. Additionally, these step angles were correlated with the Unified Parkinson's Disease Rating Scale, Part III score: mean step angle (single task: r=-0.60, P<.001; dual task: r=-0.52, P<.001), initial step angle (single task: r=-0.35, P=.006; dual task: r=-0.35, P=.01), and last step angle (single task: r=-0.43, P=.001; dual task: r=-0.41, P=.002). CONCLUSIONS:This pilot study demonstrated that the gait angular characteristics, as quantified by the step angles, were sensitive to the disease severity of PD and, more importantly, can capture the effects of treatments on the gait, while the traditional metrics cannot. This indicates that these metrics may serve as novel markers to help the assessment of gait in those with PD as well as the rehabilitation of this vulnerable cohort.

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E-DNA scaffold sensors and the reagentless, single-step, measurement of HIV-diagnostic antibodies in human serum.

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