Measuring biotherapeutic viscosity and degradation on-chip with particle diffusometry.

In the absence of efficient ways to test drug stability and efficacy, pharmaceuticals that have been stored outside of set temperature conditions are destroyed, often at great cost. This is especially problematic for biotherapeutics, which are highly sensitive to temperature fluctuations. Current platforms for assessing the stability of protein-based biotherapeutics in high throughput and in low volumes are unavailable outside of research and development laboratories and are not efficient for use in production, quality control, distribution, or clinical settings. In these alternative environments, microanalysis platforms could provide significant advantages for the characterization of biotherapeutic degradation. Here we present particle diffusometry (PD), a new technique to study degradation of biotherapeutic solutions. PD uses a simple microfluidic chip and microscope setup to calculate the Brownian motion of particles in a quiescent solution using a variation of particle image velocimetry (PIV) fundamentals. We show that PD can be used to measure the viscosity of protein solutions to discriminate native protein from degraded samples as well as to determine the change in viscosity as a function of therapeutic concentration. PD viscosity analysis is applied to two particularly important biotherapeutic preparations: insulin, a commonly used protein for diabetic patients, and monoclonal antibodies which are an emerging class of biotherapeutics used to treat a variety of diseases such as autoimmune disorders and cancer. PD-based characterization of solution viscosity is a new tool for biotherapeutic analysis, and owing to its easy setup could readily be implemented at key points of the pharmaceutical delivery chain and in clinical settings.

Constraints on priming in spatial memory: naturally learned versus experimentally learned environments.

In four experiments, we explored constraints on priming in spatial memory. In Experiments 1 and 2, subjects who were familiar with the locations of buildings on the Vanderbilt campus participated in a recognition test. The subjects' task was to decide whether or not named buildings were on the campus. Foils in this recognition test were realistic but fictional names of buildings. In principle, the subjects could have performed this task without using spatial knowledge; in fact, they must not have used spatial knowledge, because there was no evidence of priming in recognition as a function of the spatial relations between buildings on the campus. This result differs from those obtained in earlier experiments that have examined memory of spatial layouts learned in laboratory settings. In Experiment 3, the fictional foils were replaced by names of buildings in an area of the campus separated geographically from the main campus. Evidently, this change induced subjects to retrieve spatial knowledge, because the spatial priming effect materialized. A fourth experiment replicated the above findings in a single experiment and demonstrated that spatial priming could be obtained when the configuration of buildings was learned experimentally. These results are explained by appealing to the "decontextualization" that takes place in memory over time.

Methodological problems with the use of the retroactive interference design to infer what is stored.

The retroactive interference paradigm has been used in a variety of settings to investigate the nature of the representation of memory. Much of the research using this paradigm is methodologically flawed because it involves treatment comparisons which are inappropriate. It is argued that comparisons must be made between presentation conditions having the same interpolated activity and that, in addition, evidence is required that the differences are not confounded by acquisition level differences if one is to infer mode-specific interference and representation. The methodological issues are discussed in detail and the utility of the retroactive interference design is questioned. Studies employing the design are reviewed, and several conclusions are drawn: (1) there has been no unambiguous demonstration of visual mode-specific interference, (2) there has been no clear demonstration that imagery instructions produce memories that are more susceptible to visual than to auditory interpolation, and (3)no clear demonstrations are yet available that memory for spatial location is more susceptible to visual interference than memory for letters.

Presentation modality, rehearsal-prevention conditions, and auditory confusions in tests of short-term memory.

Ss were presented four-letter sequences either auditorily or visually and asked for ordered recall after 0, 2.1, 4.2, 8.4, or 12.6 sec of digit categorization. Three different rehearsal-prevention conditions were required during presentation of the memory set: categorizing, suppressing (saying "dah"), or pronouncing each letter. Recall was worst after categorizing, best after pronouncing. Auditory presentation led to better recall after no delay but more rapid forgetting than visual presentation, regardless of the rehearsal-prevention condition. These results, and analyses of auditory confusions, are inconsistent with a view of memory which asserts that sensory information is encoded auditorily regardless of presentation modality or vocalization behavior during presentation.