Elevating sampling

Abstract

Sampling – the process of collecting, preparing, and introducing an appropriate volume element (voxel) into a system – is often under appreciated and pushed behind the scenes in lab-on-a-chip research. What often stands in the way between proof-of-principle demonstrations of potentially exciting technology and its broader dissemination and actual use, however, is the effectiveness of sample collection and preparation. The power of micro- and nanofluidics to improve reactions, sensing, separation, and cell culture cannot be accessed if sampling is not equally efficient and reliable. This perspective will highlight recent successes as well as assess current challenges and opportunities in this area.

Blood, sweat, and tears: developing clinically relevant protein biosensors for integrated body fluid analysis

“…2,[16][17][18][19] However, given that the blood volume of a human is on the order of 5 L, and the interstitial fluid volume is ∼17 L, 20 the relatively low abundance of these biomarkers leads to an inexorable statistical sampling issue which cannot be solved without addressing the limitations of bulk fluid sampling. As elegantly described by Labuz et al 10 and Mariella et al 11 Poisson statistics dictates that as analyte concentration is reduced, the probability increases that a collected sample of body fluid does not contain any analyte (37% from 1 mL of sample containing a concentration of 1000 molecules per L). Unchecked, this would (or possibly already has, in some circumstances) lead to a stochastic distribution of false negative results, which have nothing to do with the downstream assays chemistry or detector sensitivity -it is simply that the sample volume may not contain the analyte.…”

“…Unchecked, this would (or possibly already has, in some circumstances) lead to a stochastic distribution of false negative results, which have nothing to do with the downstream assays chemistry or detector sensitivity -it is simply that the sample volume may not contain the analyte. This could certainly be the case in the emerging areas of ultra-sensitive protein detection (<fg mL −1 ), 21 circulating tumor cells (<50 cells per mL), 10 and microbial sepsis (<100 cfu mL −1 ).…”

“…24 There is already evidence that this problem affects the performance of biosensors exposed to body fluids, even those diluted or otherwise treated to account somewhat for the variation. 10 Taking blood as a case in point, many studies have identified changes in biomarker levels as a function of time to analysis, 25,26 different collection tubes and associated fittings, 12,25 and the degree of hemolysis (ruptured red cells leak hemaglobin into serum/plasma which changes colour of the sample leading to inaccurate results in optical assays 12 ), which is in turn affected by the sampling method, sampling site, needle gauge, collection flow rate and the size/flow properties of the specific vein involved. Clearly, attempts to address the issue of pre-analytical variability at the sampling stage could pass "savings" on downstream.…”

“…9 However, progress at the sampling stage lags behind both the assay chemistry and detection methods in terms of research output and perceived importance. 10,11 Accordingly, the majority of sample collection and processing techniques, for any class of analyte, are still reliant on 20 th , and in some cases, 19 th century technology (e.g. needles and blood tubes 12 ).…”

Microalgae: Current Research and Applications

“…Many individual microfluidic components have been presented but major challenges still lie with sample preparation (Labuz and Takayama, 2014;Mariella, 2008) and system integration (Nge et al, 2013). Nevertheless, advances in the lab-on-chip field by 2014 have made the possibility of microfluidic devices becoming widely-used products a not too distant reality (Whitesides, 2014).…”