Pen Technologies Research Articles

P-2109. Culture-Free Identification of Microbes in Seconds Directly from Clinical Samples using the MasSpec Pen Technology

Abstract Background Broad spectrum antibiotics are often used empirically in cases of suspected invasive infection requiring surgical intervention while awaiting results of conventional testing (cultures and molecular tests). Rapid and accurate diagnosis of the etiologic pathogens is critical to allow for selection of targeted antibiotics and improve outcomes for patients. We present current results of a large, multi-center clinical study using the MasSpec Pen (MSPen) technology to characterize the metabolic profiles of clinically relevant microbes in culture isolates and apply the technology to culture-independent identification of infectious agents directly in clinical samples.Figure 1.Schematics showing the key operating steps and results when using the MasSpec Pen to perform analysis and identification of bacteria. Methods The MSPen allows direct sample analysis using a solvent droplet followed by immediate mass spectrometry analysis, with total acquisition time of ∼15 seconds (fig 1). In this study 785 samples (635 isolates and 150 clinical specimens) were analyzed using this technology to create distinct metabolic profiles to differentiate bacterial pathogens. 80% of data were used as a training set to develop such profiles; 20 percent of data were used as a test set to identify bacterial infection.Fig 2.Species identification in pure isolates Results We identified over 400 bacterial metabolites and lipids in 10 different microbial species and compiled a unique metabolic profile for each that was used to directly identify specific microbes in cultures and clinical specimens. Among culture isolates, our statistical classifiers were able to achieve 99% accuracy for Gram-typing, and 99% accuracy among 10 bacteria in the test set (fig 2). Using species-specific metabolites and lipids, we were able to identify Pseudomonas aeruginosa directly from 3 infected specimens and Staphylococcus epidermidis directly from infected bone. Conclusion Our results show the incredible promise that direct MSPen analysis has for rapid, culture-independent identification of bacteria from patient tissues. We are working to build classifiers to differentiate bacteria by specific m/z values to improve identification in tissue samples. Disclosures Manoj Kumar, PhD, LSE is an inventor in patents related to the MSPen technology owned by University of Texas Austin and Baylor College of Medicine. LSE is a co-founder,: LSE is an inventor in patents related to the MSPen technology owned by University of Texas Austin and Baylor College of Medicine. LSE is a co-founder, Lindsey M. Kirkpatrick, DO, PhD, Thermo Fisher Scientific: Honoraria Michael Keating, PhD, MS Pen Technologies: Advisor/Consultant Livia Eberlin, PhD, Merck: Honoraria

P‐79: A Study of Prediction Model for Active Pen Coordinate Based on Machine Learning Algorithm

Among digital pen technologies, Active Pen has the advantage of no additional price increase in functional implementation because it commonly uses capacitance touch sensors. However, since sensors designed for finger recognition purposes are used, coordinate accuracy is relatively low compared to digital pen technology that uses dedicated sensors. Therefore, in order to overcome these limitations, this paper studies the Active Pen position prediction algorithm by applying machine learning techniques. The R2 of the model derived in this study was about 0.999, and the RMSE of the predicted position was calculated to be about 10um.

Cognitive behavior during consecutive interpreting: Describing the notetaking process

Digital pen technologies have enabled new forms of interpreting and provided new ways to train interpreting students in consecutive interpreting; however, digital pens also provide an opportunity to collect interpreting process data that can serve as a proxy for cognitive behavior. This article examines the extant literature on notetaking and cognition to advocate for using digital pens to document the notetaking process and describes several ways in which this notetaking data can be analyzed to understand interpreter behavior. In addition, several potential research avenues are outlined to enhance the methodological tools available to undertake interpreting process research in dialogue and consecutive interpreting.

One material, many possibilities via enrichment of luminescence in La2Zr2O7:Tb3+ nanophosphors for forensic stimuli aided applications

Engineering a single material with multidirectional applications is crucial for improving productivity, low cost, flexibility, least power consumption, etc. To achieve these requirements, novel design structures and high-performance materials are in urgent need. Lanthanide-doped nanophosphors have the greatest strengths and ability in order to tune their applications in various dimensions. However, applications of nanophosphor in latent fingerprints visualization, anti-counterfeiting, and luminescent gels/films are still in their infancy. This study demonstrated a simple strategy to enhance the luminescence of Tb3+ (1–11 mol %) doped La2Zr2O7 nanophosphors by conjugating various fluxes via a simple solution combustion route. The photoluminescence emission spectra reveal intense peaks at ~ 491, 546, 587, and 622 nm, which arises from 5D4 → 7FJ (J = 6, 5, 4, 3) transitions of Tb3+ ions, respectively. The highest emission intensity was achieved in the NH4Cl flux assisted nanophosphor as compared to NaBr and NH4F assisted samples. The colorimetric images of fingerprints visualized using the optimized nanophosphor on forensic related surfaces exhibit level –III ridge details, including sweat pores, the width of the ridges, bifurcation angle, and the successive distance between sweat pores, etc. These results are decisive parameters that clearly support the statement “no two persons have ever been found to have the same fingerprints”. The anti-counterfeiting security ink was formulated using optimized nanophosphor and various patterns were designed by simple screen printing and dip pen technologies. The encoded information was decrypted only under ultraviolet 254 nm light. All the designed patterns are exhibit not just what it looks/feel like and how better it works. As a synergetic contribution of enhanced luminescence of the prepared nanophosphor, the green-emissive films were fabricated, which display excellent flexibility, uniformity, and transparency in the normal and ultraviolet 254 nm light illumination. The aforementioned results revealed that the prepared NH4Cl flux-assisted La2Zr2O7: Tb3+(7 mol %) NPs are considered to be the best candidate for multi-dimensional applications.

662. Identification of Clinically Relevant Microbes with the MasSpec Pen

BackgroundIn the age of antimicrobial resistance, rapid identification of infectious agents is critical for antimicrobial stewardship and effective therapy. To this end, ambient ionization mass spectrometry techniques have been applied for rapid identification of microbes directly from culture isolates. We have developed a handheld, mass spectrometry-based device, the MasSpec Pen, that permits direct molecular analysis of a biological sample in seconds (Scheme 1). Here, we employ the MasSpec Pen to identify clinically relevant microbes directly from culture isolates.Methods Staphylococcus aureus, Staphylococcus epidermidis, Group A and B Streptococcus, Kingella kingae (K.k), and Pseudomonas aeruginosa (P.a) were cultured on 5% sheep’s blood nutrient agar at 37 °C overnight. Colonies were transferred to a glass slide where they were analyzed directly with the MasSpec Pen coupled to a Q Exactive mass spectrometer (Thermo Scientific) in negative ion mode. For MasSpec Pen analysis, a 10 µL droplet of water was held in contact with the sample surface for 3 seconds and then aspirated to the mass spectrometer for analysis.Data was normalized and the molecular features resulting from the analysis solvent and nutrient medium were removed. The least absolute shrinkage and selection operator (lasso) statistical method was used to build classification models for prediction of bacterial identity. Model performance was evaluated by leave-one-out cross-validation and a validation set of samples.Scheme 1: MasSpec Pen workflow ResultsVarious small molecules were detected including metabolites and glycerophospholipid species. The mass spectral profiles for each species exhibited qualitative differences among them (Figure 1). Additionally, several quorum-sensing molecules were observed in P.a. including hydroxy-heptyl-quinoline (m/z 242.155).Lasso statistical classifiers were created to differentiate organisms at the level of Gram type, genus, and species with each model comprised of a sparse set of molecular features. Accuracies of 90% or greater were achieved for all lasso models and as high as 98% for the differentiation of Staphylococcus (Staph.) and Streptococcus (Strep.).Figure 1: Molecular profiles of species analyzed Figure 2: Statistical classification results ConclusionThese results demonstrate the potential of the MasSpec Pen as a tool for clinical analysis of infected biospecimens.DisclosuresSydney C. Povilaitis, BA, MS Pen Technologies, Inc. (Other Financial or Material Support, Patent) Livia Eberlin, PhD, MS Pen Technolpogies, Inc. (Board Member, Shareholder)

Enhancement of English learning performance by using an attention-based diagnosing and review mechanism in paper-based learning context with digital pen support

Since English is probably the most popular second language, helping students learn English through technology is a critical issue in non-English-speaking countries. With the growth of digital pen technologies, developing an interactive learning environment that combines printed textbooks and a digital pen to support English-language classroom learning has become feasible. This work presents an attention-based diagnosing and review mechanism (ADRM) based on brainwave detection to help learners identify the passages with low attention level in a lesson as review targets in order to perform efficiently and accurately review processes while reading paper-based English texts with digital pen support in autonomous learning environments. Based on the true experimental design, this work aims to confirm whether the ADRM improves the review performance and sustained attention of learners while reading paper-based English texts with digital pen support. The research participants were a total of 108 students at an industrial vocational high school in Taipei City, Taiwan. All research participants were male and aged from 17 to 18 years. The experimental group used the ADRM while reading paper-based English texts with digital pen support, whereas the control group used the autonomous review while reading paper-based English texts with digital pen support. Experimental results reveal that the review performance of the experimental group was significantly better than that of the control group, proving that the ADRM improved review performance. The results also show that the field-dependent learners in the experimental group exhibited a great improvement in review performance in comparison with the field-independent learners. Additionally, the low-ability learners in the experimental group exhibited better review performance compared to those in the control group. Furthermore, learners with high attention level in the experimental group have exhibited better review performance and sustained attention than the learners in the control group. This work confirms that developing an ADRM based on brainwave detection to assist learners’ review processes is practicable. However, the usability and acceptability of using ADRM instead of human autonomous review should be further considered in the information society.

A microdestructive capillary electrophoresis method for the analysis of blue-pen-ink strokes on office paper

This manuscript describes the development of a capillary electrophoresis (CE) method for the detection of acid and basic dyes and its application to real samples, blue-pen-ink strokes on office paper. First, a capillary zone electrophoresis (CZE) method was developed for the separation of basic and acid dyes, by studying the separation medium (buffer nature, pH and relative amount of additive) and instrumental parameters (temperature, voltage and capillary dimensions). The method performance was evaluated in terms of selectivity, resolution (above 5 and 2 for acid dyes and basic dyes, respectively, except for two basic dye standards), LOD (lower than 0.4mg/L) and precision as intraday and interday RSD values of peak migration times (lower than 0.6%). The developed method was then applied to 34 blue pens from different technologies (rollerball, ballpoint, markers) and with different ink composition (gel, water-based, oil-based). A microdestructive sample treatment using a scalpel to scratch 0.3mg of ink stroke was performed. The entire electropherogram profile allowed the visual discrimination between different types of ink and brands, being not necessary a statistical treatment. A 100% of discrimination was achieved between pen technologies, brands, and models, although non-reproducible zones in the electropherograms were found for blue gel pen samples. The two different batches of blue oil-based pens were also differentiated. Thus, this method provides a simple, microdestructive, and rapid analysis of different blue pen technologies which may complement the current analysis of questioned documents performed by forensic laboratories.

Tensor based non-photo realistic rendering for Korean architectural images

Existing pen and ink sketch technologies can be applied to general images, but they could not produce optimal output for images of traditional architecture, because most images consist of exquisite straight lined patterns in traditional architecture, such as root tiles and window bars. The lines of roofs and eaves need to be described delicately to express pen and ink sketch most effectively. Therefore, by proposing a method to create white noise for light and shade of input images, to extract input vector directions from the white noise, and to determine the direction and length of stroke, a new expression technique is proposed for pen and ink sketch that could best reflect the characteristics of traditional architecture.

The new chalkboard: the role of digital pen technologies in tertiary mathematics teaching

Traditional classroom teaching environments have used board technologies to incorporate handwritten elements within multimodal pedagogical approaches to developing mathematical thinking. In the tertiary sector, increasing use of computing technologies based on keyboard and mouse interfaces and learning environments that emphasize digital displays constrain the use of handwritten elements. This article discusses how the use of pen-enabled Tablet PCs can provide support for handwritten elements, to build on the benefits of traditional pedagogical approaches and facilitate the development of new approaches.

Facilitating English-language learners' oral reading fluency with digital pen technology

Oral reading fluency is an indicator of overall reading competence. Many studies have claimed that repeated reading can promote oral reading fluency. Currently, novel Web- or computer-based reading technologies offer interactive digital materials that promote English oral reading fluency using the repeated reading strategy; however, paper-based English materials in physical classrooms are still used to train students in oral reading fluency because most students are used to learning environments with paper, pen, and face-to-face interaction. With the growth of digital pen technologies, developing an interactive learning environment that combines printed textbooks and a digital pen to support English-language classroom learning has become feasible. Thus, this work presents a digital pen and paper interaction platform (DPPIP) composed of a student-learning tier, course management tier, and teacher tutoring tier, in which digital pen technologies are integrated with printed textbooks and Moodle course management system, to support the repeated reading strategy for promoting English-language oral reading fluency, learning motivation, and learning satisfaction. Meanwhile, this work also examined whether the proposed DPPIP provides different benefits in terms of the promotion of the oral reading fluency to students with field-dependent and field-independent cognitive styles. Based on the non-equivalent control group design in the quasi-experimental research, this work recruited two junior high school classes from Taoyuan County, Taiwan, to participate in an instructional experiment. One class was randomly assigned to the experimental group, which used the DPPIP to perform the repeated reading strategy in order to enhance English-language oral reading fluency. By contrast, the other class was assigned to the control group, which adopted the traditional paired reading method to support the repeated reading strategy to improve English-language oral reading fluency. Analytical results show that applying the proposed DPPIP to support a regular English-language course in classrooms had significantly positive effects in promoting the English-language oral reading fluency, learning motivation, and learning satisfaction of junior high school students. Moreover, this DPPIP simultaneously helped the experimental group students with the field-independent and field-dependent cognitive styles accelerate their oral reading fluency. Importantly, the oral reading fluency of the experimental group students is positively correlated with the frequency which the digital pen was used.

Interactive whiteboards: Real beauty or just “lipstick”?

There has been extensive investment by governments and individual schools in interactive whiteboard technology in developed countries premised on the assumption that their use in education will impact positively on learners’ achievements. Developing countries, such as South Africa, keen to raise attainment among their learners are following suit. While at least one of the nine provinces in South Africa had undertaken pilot roll-outs of interactive whiteboards (IWBs) in schools, the Eastern Cape Department of Education commissioned a feasibility study to determine teachers and learners perceptions of the potential benefits and drawbacks of using interactive pen technology, specifically the eBeam, in their teaching and learning environments, before embarking upon a large scale roll-out. This paper reports on a case study of three government schools and highlights the learners and teachers’ enthusiasm about the “big screen” and the multimedia options, but also raises concerns about the lack of ICT literacy displayed by teachers and learners and the cost of technology. As most of the benefits mentioned by the teachers and learners seemed to accrue to the use of the laptop and data projector combination and most of the drawbacks emanated from the use of the interactive pen technology itself, we suggest that it may not be expeditious to attempt to “leap-frog” the use of interactive technologies. Instead we suggest that an evolution of ICT related pedagogy is necessary to make optimal use of interactive pen technologies such as the eBeam and that teachers should be offered technologies, not have them imposed upon them.

Machine learning in a multimedia document retrieval framework

The Pen Technologies group at IBM Research has recently been investigating methods for retrieving handwritten documents based on user queries. This paper investigates the use of typed and handwritten queries to retrieve relevant handwritten documents. The IBM handwriting recognition engine was used to generate N-best lists for the words in each of 108 short documents. These N-best lists are concise statistical representations of the handwritten words. These statistical representations enable the retrieval methods to be robust when there are machine transcription errors, allowing retrieval of documents that would be missed by a traditional transcription-based retrieval system. Our experimental results demonstrate that significant improvements in retrieval performance can be achieved compared to standard keyword text searching of machine-transcribed documents. We have developed a software architecture for a multimedia document retrieval framework into which machine learning algorithms for feature extraction and matching may be easily integrated. The framework provides a plug-and-play mechanism for the integration of new media types, new feature extraction methods, and new document types.

Talking and writing—how natural in human–machine interaction?

Talking and writing are activities that most humans learn at a relatively early age and carry out fairly effortlessly for the rest of their lives. It is therefore of little surprise that these activities have been considered within the context of human–machine interaction, i.e. the development of a means by which we can elicit machine actions to complete tasks through talking and writing. Given the ease and readiness with which we talk and write to each other, and the rapidly increasing use of computer technology in the developed world, it could be argued that the development of speech and pen technologies comprises a logical and worthwhile progression in HCI (human–computer interaction). It could also be argued, as many individuals have, that the naturalness of these activities in human-to-human communication makes them an obvious choice for machine interactions. The question being considered here is the extent to which speech and pen input provide a natural means of communicating with machines. No one would dispute their naturalness in human-to-human communication, but does this extend to human–machine interaction? Moreover, does the fact that we are so skilled at these activities actually work against us when we come to try these emerging technologies? And finally, how can future research lead towards achieving greater naturalness?

New user interfaces.

Usability of a computer-based information system has three components: user-friendliness, acceptance and user-competence. These are important considerations in human-computer interface designs. So far, visual/manual interface techniques have dominated data-capture activities in hospital settings. Despite the improvements made in these areas, usability issues still remain over the use of such I/O devices like the computer keyboard, touch-sensitive screens, light pen and bar codes. This paper will examine two of the newer user interfaces that have emerged in recent years which can potentially improve computer usability in the healthcare setting. These are voice and pen technologies. Speech as a medium for communicating with computers has several advantages. It gives users freedom of movement away from a computer terminal. It further allows users to enter or receive data while engaged in other activities. For example, a doctor can simultaneously examine a patient and record his findings using voice input. The use of pen technology also liberates the physician and other healthcare workers from the keyboard and monitor. It gives them mobility, facilitates eye contact with patients and most importantly, allows them to tap the newest of computer hardware and software technology with the oldest of communication tools--the pen. Healthcare facilities are beginning to explore the use of these two technologies to improve on user-acceptance and user-competence. Some examples of their successful applications will be given.

Intelligent Medical Record--entry (IMR-E).

This paper describes an automated medical record designed to allow providers to enter patient data at the point of care. The system runs on PCs and Macintoshes and uses a graphical user interface and object-oriented programming to take advantage of current mouse and pen technologies. The provider acquires all relevant patient data by pointing and clicking at selections on input screens, many of which contain anatomical drawings to help the provider quickly and accurately describe patient findings. The system also generates a grammatically correct progress note using the problem-oriented structure. Furthermore, items identified in the assessment and plans portion of the program can be ported to expert systems for medical decisions assistance or to billing systems. The system allows the provider to obtain the necessary information on a focused patient visit in less than 5 min or to enter a complete history and physical.