Download Week 41 (2015-10-05)

Biobank literature update week 40 (2015)
[1] Integration, Networking, and Global Biobanking in the Age of New Biology. Karimi-Busheri F, Rasouli-Nia A.
Advances in experimental medicine and biology 2015; 864:1-9. Scientific revolution is changing the world forever. Many
new disciplines and fields have emerged with unlimited possibilities and opportunities. Biobanking is one of many that is
benefiting from revolutionary milestones in human genome, post-genomic, and computer and bioinformatics
discoveries. The storage, management, and analysis of massive clinical and biological data sets cannot be achieved
without a global collaboration and networking. At the same time, biobanking is facing many significant challenges that
need to be addressed and solved including dealing with an ever increasing complexity of sample storage and retrieval,
data management and integration, and establishing common platforms in a global context. The overall picture of the
biobanking of the future, however, is promising. Many population-based biobanks have been formed, and more are
under development. It is certain that amazing discoveries will emerge from this large-scale method of preserving and
accessing human samples. Signs of a healthy collaboration between industry, academy, and government are
encouraging.
[2] The Future of Biobanking: A Conceptual Look at How Biobanks Can Respond to the Growing Human Biospecimen
Needs of Researchers. Somiari SB, Somiari RI. Advances in experimental medicine and biology 2015; 864:11-27.
Biobanking of human biological specimens has evolved from the simple private collection of often poorly annotated
residual clinical specimens, to well annotated and organized collections setup by commercial and not-for-profit
organizations. The activities of biobanks is now the focus of international and government agencies in recognition of the
need to adopt best practices and provide scientific, ethical and legal guidelines for the industry. The demand for more,
high quality and clinically annotated biospecimens will increase, primarily due to the unprecedented level of genomic,
post genomic and personalized medicine research activities going on. Demand for more biospecimens provides new
challenges and opportunities for developing strategies to build biobanking into a business that is better able to supply
the biospecimen needs of the future. A paradigm shift is required particularly in organization and funding, as well as in
how and where biospecimens are collected, stored and distributed. New collection sites, organized as Research Ready
Hospitals (RRHs) and new public-private partnership models are needed for sustainability and increased biospecimen
availability. Biobanks will need to adopt industry-wide standard operating procedures, better and "non-destructive"
methods for quality assessment, less expensive methods for sample storage/distribution, and objective methods to
manage scarce biospecimens. Ultimately, the success of future biobanks will rely greatly on the success of public-private
partnerships, number and diversity of available biospecimens, cost management and the realization that an effective
biobank is one that provides high quality and affordable biospecimens to drive research that leads to better health and
quality of life for all.
[3] Sustainability of Biobanks in the Future. De Souza YG. Advances in experimental medicine and biology 2015; 864:2935. Human biorepositories are essential in providing high quality specimens that are well characterized. Biospecimens
are used in basic, clinical, and translational research. However, as regulatory requirements and scientific demands
increase the complexity of the daily operations of a biorepository, the cost of maintaining a biobank will increase. How
can biobanks today maintain sustainability during the current economic climate and changing landscape of operating a
biorepository? This is a brief review of how different biobanks have approached sustainability.
[4] Biobanking: The Future of Cell Preservation Strategies. Baust JM, Corwin WL, VanBuskirk R, Baust JG. Advances in
experimental medicine and biology 2015; 864:37-53. With established techniques cryopreservation is often viewed as an
"old school" discipline yet modern cryopreservation is undergoing another scientific and technology development
growth phase. In this regard, today's cryopreservation processes and cryopreserved products are found at the forefront
of research in the areas of discovery science, stem cell research, diagnostic development and personalized medicine. As
the utilization of cryopreserved cells continues to increase, the demands placed on the biobanking industry are
increasing and evolving at an accelerated rate. No longer are samples providing for high immediate post-thaw viability
adequate. Researchers are now requiring samples where not only is there high cell recovery but that the product
recovered is physiologically and biochemically identical to its pre-freeze state at the genominic, proteomic, structural,
functional and reproductive levels. Given this, biobanks are now facing the challenge of adapting strategies and
protocols to address these needs moving forward. Recent studies have shown that the control and direction of the
Biobank literature update week 40 (2015)
molecular response of cells to cryopreservation significantly impacts final outcome. This chapter provides an overview of
the molecular stress responses of cells to cryopreservation, the impact of the apoptotic and necrotic cell death
continuum and how studies focused on the targeted modulation of common and/or cell specific responses to freezing
temperatures provide a path to improving sample quality and utility. This line of investigation has provided a new
direction and molecular-based foundation guiding new research, technology development and procedures. As the use of
and the knowledge base surrounding cryopreservation continues to expand, this path will continue to provide for
improvements in overall efficacy and outcome.
[5] Biobanking for Personalized Medicine. Liu A, Pollard K. Advances in experimental medicine and biology 2015;
864:55-68. A biobank is an entity that collects, processes, stores, and distributes biospecimens and relevant data for use
in basic, translational, and clinical research. Biobanking of high-quality human biospecimens such as tissue, blood and
other bodily fluids along with associated patient clinical information provides a fundamental scientific infrastructure for
personalized medicine. Identification of biomarkers that are specifically associated with particular medical conditions
such as cancer, cardiovascular disease and neurological disorders are useful for early detection, prevention, and
treatment of the diseases. The ability to determine individual tumor biomarkers and to use those biomarkers for disease
diagnosis, prognosis and prediction of response to therapy is having a very significant impact on personalized medicine
and is rapidly changing the way clinical care is conducted. As a critical requirement for personalized medicine is the
availability of a large collection of patient samples with well annotated patient clinical and pathological data, biobanks
thus play an important role in personalized medicine advancement. The goal of this chapter is to explore the role of
biobanks in personalized medicine and discuss specific needs regarding biobank development for translational and
clinical research, especially for personalized medicine advancement.
[6] A Global View of Breast Tissue Banking. Wilson H, Botfield B, Speirs V. Advances in experimental medicine and
biology 2015; 864:69-77. The importance of accessing high quality clinical samples for translational research is now
firmly recognised. Traditionally these samples were collected and curated by individuals with an interest in a particular
disease type. In recent years the idea of centralising and storing tissue collections in the form of tissue banks or biobanks
has developed. As a result a number of biobanks have been established in many different countries. These can be either
single centres or multi centre collaborations, often in the form of a federated network. This chapter outlines the
development of breast tissue banking in a global context and discusses some of the challenges that lie ahead for the
field, in particular how to meet the growing needs of researchers, how to make the best use of donated samples and
how to increase the visibility of samples residing in biobanks to researchers.
[7] Biobanking of Cerebrospinal Fluid for Biomarker Analysis in Neurological Diseases. Willemse EA, Teunissen CE.
Advances in experimental medicine and biology 2015; 864:79-93. Cerebrospinal fluid (CSF) reflects pathophysiological
aspects of neurological diseases, where neuroprotective strategies and biomarkers are urgently needed. Therefore,
biobanking is very relevant for biomarker discovery and evaluation for these neurological diseases.An important aspect
of CSF biobanking is quality control, needed for e.g. consistent patient follow-up and the exchange of patient samples
between research centers. Systematic studies to address effects of pre-analytical and storage variation on a broad range
of CSF proteins are needed and initiated.Important features of CSF biobanking are intensive collaboration in
international networks and the tight application of standardized protocols. The current adoption of standardized
protocols for CSF and blood collection and for biobanking of these samples, as presented in this chapter, enables
biomarker studies in large cohorts of patients and controls.In conclusion, biomarker research in neurodegenerative
diseases has entered a new era due to the collaborative and multicenter efforts of many groups. The streamlining of
biobanking procedures, including sample collection, quality control, and the selection of optimal control groups for
investigating biomarkers is an important improvement to perform high quality biomarker studies.
[8] Biobanking in the Twenty-First Century: Driving Population Metrics into Biobanking Quality. Roberts JN, Karvonen
C, Graham K et al. Advances in experimental medicine and biology 2015; 864:95-114. Biospecimens are the essential
substrates for human biomarker research. Across the globe, biobanks have developed the facilities and mechanisms to
Biobank literature update week 40 (2015)
collect, process, store and distribute those substrates to researchers. However, despite some notable successes, less
than one hundred of the tens of thousands of purported biomarkers have been independently validated. We propose
the need for a new paradigm in biobanking; simply pursuing larger numbers of participants, larger networks of biobanks
and higher sample integrity will not, in itself, transform the success rate or efficiency of biomarker research. We propose
that biobanks must embrace the intrinsic observational nature of biospecimens and furnish the recipients of
biospecimens with the population metrics (descriptive statistics) that can facilitate the scientific rigor that is mandated
in other areas of observational research. In addition, we discuss the value of population-based ascertainment and
recruitment and the importance of the timing of biospecimen collections. Any assessment of biospecimen quality must
go beyond the sample itself and consider both the patient/participant selection and the most appropriate and
informative timing for specimen collection, particularly prior to any treatment intervention in diseased populations. The
examples and rationales that we present are based largely on cancer-related collections because the feasibility of
population metrics is greatly assisted by the comprehensive registries that are more common for cancer than other
chronic diseases. Changing the biobanking paradigm from tacitly 'experimental' to explicitly 'observational' represents a
profound but urgent methodological shift that will influence the establishment, management, reporting and impact of
biobanks in the twenty-first century.
[9] Challenges in Developing a Cancer Oriented-Biobank: Experience from a 17 Year-Old Cancer Biobank in Sao Paulo,
Brazil. Campos AH, Soares FA. Advances in experimental medicine and biology 2015; 864:115-123. Brazil and Latin
America will face a cancer epidemic in the coming years. Efforts towards cancer prevention, early detection and
treatment must be associated with active research that helps understanding the geographical variations of this disease.
The creation of cancer-oriented biobanks should be part of this strategy. This article outlines the challenges of
establishing a cancer-oriented biobank at the A. C. Camargo Center, a private, non-profit institution located in Sao Paulo,
Brazil. We analyze important issues related to the day-to-day operations of the biobank within an institutional and
national context, as well as the lessons learned over the years. It is hoped that the information contained in this paper
will be useful for the development of other biobanks in Brazil and other countries in Latin America.
[10] China Biobanking. Zhang Y, Li Q, Wang X, Zhou X. Advances in experimental medicine and biology 2015; 864:125140. Biobanks are playing increasingly important roles in clinical and translational research nowadays. China, as a
country with the largest population and abundant clinical resources, attaches great importance to the development of
biobanks. In recent years, with the increasing support from the Chinese government, biobanks are blooming across the
country. This paper provides a detailed overview of China biobanking, which is further divided in the following four
parts: (i) general introduction of the number, category and distribution of current biobanks; (ii) summarization of the
current development status, and issues that Chinese biobanks are faced with; (iii) international cooperation between
China and the global biobanking community; (iv) prospect of the modern twenty-first century Chinese biobanks, which
would achieve standardized operation, systematic specimen management, and extensive collaboration, and thus
provide support for the robust research discoveries and personalized medicine etc.
[11] Establishing an Iso-Compliant Modern Cancer-Biobank in a Developing Country: A Model for International
Cooperation. Sughayer MA, Souan L. Advances in experimental medicine and biology 2015; 864:141-155. King Hussein
Cancer (KHCC) is a specialized cancer center that treats both adult and pediatric cancer patients from Jordan and the
neighboring countries. KHCC is acknowledged as a leader in cancer treatment in the Middle East and its vision is to
maintain its leading position in cancer therapy and research. Hence, KHCC embarked on establishing the first ISO
compliant cancer biobank (KHCCBIO) in Jordan.Currently, there are very few biobanks in the Middle East, hence, KHCC
wanted to change this situation by establishing an ISO-compliant cancer biobank which would incorporate all current
international guidelines and best-in class practices under an approved quality management system for the benefit of
researchers in Jordan, its neighboring countries, and throughout the world. The established biobank would follow the
highest ethical standards in collecting, processing, storing and distributing high-quality, clinically annotated
biospecimens.The strategy used in establishing KHCCBIO was based on taking advantage of international networking and
collaboration. This in essence led to knowledge transfer between well established organizations, institutions and
individuals from Europe and Jordan, in existing technological innovation and internationally recognized quality
Biobank literature update week 40 (2015)
standards. KHCC efforts were facilitated by a grant from the European Union under the seventh frame work
program.Future aims of KHCCBIO are to develop KHCC's research infrastructure, increase its scope and visibility and
improve its competitiveness throughout the biomedical science arena. Moreover, KHCCBIO is aiming to establish a
platform for future knowledge transfer and collaborative research; develop partnerships between European and Middle
Eastern organizations.
[12] Nursing and Biobanking. Sanner J, Yu E, Nomie K. Advances in experimental medicine and biology 2015; 864:157163. Nurses are a pivotal component of the translational research movement and apply scientific discoveries to the
healthcare and clinical practice fields. Biobanking is also an important factor in furthering translational research by
providing biospecimens and related clinical data to the research community. The effectiveness of any biobanking effort
necessitates the enrollment of large numbers of diverse participants, which signifies a need for the nursing profession to
secure the knowledge necessary to impact biobanking practices and to promote participant advocacy. In addition,
biobanks provide the volume, variety, veracity, and velocity of data that can address the challenges of nursing research.
Nurse scientists, research nurse coordinators and clinical research and practice nurses must be informed about the
various benefits and risks associated with biobanking in addition to ethical issues surrounding informed consent,
participant privacy, and the release of research results. Ultimately, nurses need to possess competencies to facilitate
biobanking practices both at the research bench and at the point of care.
[13] A Data-Centric Strategy for Modern Biobanking. Quinlan PR, Gardner S, Groves M et al. Advances in experimental
medicine and biology 2015; 864:165-169. Biobanking has been in existence for many decades and over that time has
developed significantly. Biobanking originated from a need to collect, store and make available biological samples for a
range of research purposes. It has changed as the understanding of biological processes has increased and new sample
handling techniques have been developed to ensure samples were fit-for-purpose.As a result of these developments,
modern biobanking is now facing two substantial new challenges. Firstly, new research methods such as next generation
sequencing can generate datasets that are at an infinitely greater scale and resolution than previous methods. Secondly,
as the understanding of diseases increases researchers require a far richer data set about the donors from which the
sample originate.To retain a sample-centric strategy in a research environment that is increasingly dictated by data will
place a biobank at a significant disadvantage and even result in the samples collected going unused. As a result
biobanking is required to change strategic focus from a sample dominated perspective to a data-centric strategy.
[14] The Importance of Quality Patient Advocacy to Biobanks: A Lay Perspective from Independent Cancer Patients
Voice (ICPV), Based in the United Kingdom. Wilcox M, Grayson M, MacKenzie M et al. Advances in experimental
medicine and biology 2015; 864:171-183. Biobanking in the twentieth century will become of increasing importance in
health research. Regulation and governance of biobanks must be open and transparent to ensure public trust and
confidence and increase donation. Effective Lay Involvement all levels in biobank organisations should be standard
practice helping ensure patient benefit remains the central aim and assisting the Promotion of Biobanks and
Recruitment of Donors. Properly selected, educated and supported, they become valued members of the Biobank Team.
This chapter is based on the work of Independent Cancer Patients' Voice (ICPV) in the UK and recognises that the
National Health Service provides a framework which is not universal and neither is the model of patient advocacy which
has been developed particularly in cancer research. However, although it has not been easy to find potential members
for ICPV, nor to attract funding, we have earned the respect of our professional colleagues by our commitment in giving
time and developing the skills necessary to provide effective involvement. These colleagues have enthusiastically
mentored and supported us and have provided venues and tutoring for Educational Events. We are sure that patient
advocates in other countries would welcome the opportunity for similar involvement and hope our experiences will be
of interest.
[15] Thermal Pretreatment Improves Viability of Cryopreserved Human Endothelial Cells. Hofmann N, Sun H,
Chatterjee A et al. Biopreserv Biobank 2015. A high survival rate of cryopreserved cells requires optimal cooling and
thawing rates in the presence of a cryoprotective agent (CPA) or a combination of CPAs in adequate concentrations. One
Biobank literature update week 40 (2015)
of the most widely used CPAs, dimethyl sulfoxide (Me2SO), however is toxic at high concentrations and has detrimental
effects on cellular functions. Additional processing steps are necessary to remove the CPA after thawing, which make
the process expensive and time consuming. Therefore it is of great interest to develop new cryoprotective strategies to
replace the currently used CPAs or to reduce their concentration. The aim of this study was to investigate if thermal
activation of human pulmonary microvascular endothelial cells (HPMEC ST-1.6R), prior to cryopreservation, could
improve their post-thaw viability since the resulting heat shock protein expression acts as an intrinsic cellular protection
mechanism. The results of this study suggest that both heat and cold shock pretreatments improve cryopreservation
outcome of the HPMEC ST-1.6R cells. By re-cultivating cells after heat shock treatment before cryopreservation, a
significant increase in cellular membrane integrity and adherence capacity could be achieved. However a combination of
thermal activation and cryopreservation with alternative CPAs such as ectoine and L-proline could not further enhance
the cell viability. The results of this study showed that pretreatment of endothelial cells with thermal activation could be
used to reduce the Me2SO concentration required in order to preserve cell viability after cryopreservation.
[16] A Model to Estimate Frozen Tissue Collection Targets in Biobanks to Support Cancer Research. Meredith AJ, Slotty
A, Matzke L et al. Biopreserv Biobank 2015. Human biospecimens are used in 40% of cancer research publications.
Tumor biobanks are an important source for these biospecimens and support both prospective and retrospective
research studies. Supporting retrospective research requires tumor tissue biobanks to accrue an adequate inventory, or
stock, of cases comprising tumor biospecimens and associated treatment and outcomes data. We propose a model to
establish appropriate targets for stocks of frozen tissue biospecimens in tumor biobanks, sufficient to support cancer
research needs. Our model considers national levels of investment in academic cancer research relative to research use
of cases described in publication output, and scales this to the local context of the BC Cancer Agency Tumour Tissue
Repository (TTR) as an example. Adjustment factors are then applied to correct for the primary intended user base of
the biobank, as well as variables intrinsic to all biobanking operations and case collection. On this basis we estimate a
current target stock for the TTR of approximately 4500 cases. Local research demand derived from case release data can
then be applied to fine-tune accrual targets and refine the biobank's relative portfolio of cases from different tumor
sites. We recognize that current targets will need regular remodeling as research demands change over time and that
our initial model has some limitations related to the need to extrapolate from available research and biobank utilization
data, and does not incorporate biospecimen/case contributions within the context of a network. However, we believe
the lack of models to estimate inventory targets for tumor biobanks and to better balance research demand with
biospecimen supply, contributes to the hesitation of funders to provide support, and also the problems of sustainability
faced by many biobanks. Creating tangible inventory targets will improve biobank efficiency, sustainability, and may also
encourage increased and stable funding.
[17] The Informatics Challenges Facing Biobanks: A Perspective from a United Kingdom Biobanking Network. Quinlan
PR, Groves M, Jordan LB et al. Biopreserv Biobank 2015. The challenges facing biobanks are changing from simple
collections of materials to quality-assured fit-for-purpose clinically annotated samples. As a result, informatics
awareness and capabilities of a biobank are now intrinsically related to quality. A biobank may be considered a data
repository, in the form of raw data (the unprocessed samples), data surrounding the samples (processing and storage
conditions), supplementary data (such as clinical annotations), and an increasing ethical requirement for biobanks to
have a mechanism for researchers to return their data. The informatics capabilities of a biobank are no longer simply
knowing sample locations; instead the capabilities will become a distinguishing factor in the ability of a biobank to
provide appropriate samples. There is an increasing requirement for biobanking systems (whether in-house or
commercially sourced) to ensure the informatics systems stay apace with the changes being experienced by the
biobanking community. In turn, there is a requirement for the biobanks to have a clear informatics policy and directive
that is embedded into the wider decision making process. As an example, the Breast Cancer Campaign Tissue Bank in the
UK was a collaboration between four individual and diverse biobanks in the UK, and an informatics platform has been
developed to address the challenges of running a distributed network. From developing such a system there are key
observations about what can or cannot be achieved by informatics in isolation. This article will highlight some of the
lessons learned during this development process.
Biobank literature update week 40 (2015)
[18] How Severely Is DNA Quantification Hampered by RNA Co-extraction? Sanchez I, Remm M, Frasquilho S et al.
Biopreserv Biobank 2015. The optional RNase digest that is part of many DNA extraction protocols is often omitted,
either because RNase is not provided in the kit or because users do not want to risk contaminating their laboratory.
Consequently, co-eluting RNA can become a "contaminant" of unknown magnitude in a DNA extraction. We extracted
DNA from liver, lung, kidney, and heart tissues and established that 28-52% of the "DNA" as assessed by
spectrophotometry is actually RNA (depending on tissue type). Including an RNase digest in the extraction protocol
reduced 260:280 purity ratios. Co-eluting RNA drives an overestimation of DNA yield when quantification is carried out
using OD 260 nm spectrophotometry, or becomes an unquantified contaminant when spectrofluorometry is used for
DNA quantification. This situation is potentially incompatible with the best practice guidelines for biobanks issued by
organizations such as the International Society for Biological and Environmental Repositories, which state that
biospecimens should be accurately characterized in terms of their identity, purity, concentration, and integrity.
Consequently, we conclude that an RNase digest must be included in DNA extractions if pure DNA is required. We also
discuss the implications of unquantified RNA contamination in DNA samples in the context of laboratory accreditation
schemes.
[19] Tensions Between Policy and Practice in Finnish Biobank Legislation. Tupasela A. Biopreserv Biobank 2015. In 2012
a new biobanking law came into effect in Finland which, according to some, is one of the most comprehensive and
broad national biobanking legislations in the world to date. The law covers both clinical and research collections and
provides institutions with great flexibility in terms of transferring existing collections into a biobank. The law also
includes provisions for individuals whose samples are stored in the biobank to request information regarding the studies
in which the sample has been used. However, this provision also compels biobanks to provide an account of the
significance of the research findings to their individual health. This legal provision has created tension between policy
and practice in that most biobanks will struggle to interpret and apply this provision in practice. The relationship
between the rights and needs to conduct research using biobank material and individual rights of access is sometimes
unclear and fraught with interpretational challenges. The derivation of national interpretations of European Directives
and Conventions gives rise to what I call interpretive regulatory dissonance. This is expected to be a challenge for
harmonizing European and global biobanking activities in the future.
[20] Caring Decisions: The Development of a Written Resource for Parents Facing End-of-Life Decisions. Xafis V, Gillam
L, Hynson J et al. Journal of palliative medicine 2015. BACKGROUND: Written resources in adult intensive care have been
shown to benefit families facing end of life (EoL) decisions. There are few resources for parents making EoL decisions for
their child and no existing resources addressing ethical issues. The Caring Decisions handbook and website were
developed to fill these gaps. AIM: We discuss the development of the resources, modification after reviewer feedback
and findings from initial pilot implementation. DESIGN: A targeted literature review-to identify resources and factors
that impact on parental EoL decision-making; development phase-guided by the literature and the researchers'
expertise; consultation process-comprised a multi-disciplinary panel of experts and parents; pilot evaluation study-hardcopy handbook was distributed as part of routine care at an Australian Children's Hospital. SETTING/PARTICIPANTS:
Twelve experts and parents formed the consultation panel. Eight parents of children with life-limiting conditions and
clinicians were interviewed in the pilot study. RESULTS: Numerous factors supporting/impeding EoL decisions were
identified. Caring Decisions addressed issues identified in the literature and by the multidisciplinary research team. The
consultation panel provided overwhelmingly positive feedback. Pilot study parents found the resources helpful and
comforting. Most clinicians viewed the resources as very beneficial to parents and identified them as ideal for training
purposes. CONCLUSIONS: The development of the resources addressed many of the gaps in existing resources. The
consultation process and the pilot study suggest these resources could be of significant benefit to parents and clinicians.
[21] Forensic uses of research biobanks: should donors be informed? Dranseika V, Piasecki J, Waligora M. Medicine,
health care, and philosophy 2015. Occasional reports in the literature suggest that biological samples collected and
stored for scientific research are sometimes accessed and used for a variety of forensic purposes. However, donors are
almost never informed about this possibility. In this paper we argue that the possibility of forensic access may constitute
a relevant consideration at least to some potential research subjects in deciding whether to participate in research. We
Biobank literature update week 40 (2015)
make the suggestion that if some type of forensic access to research collections is likely to be perceived by the subjects
as a reason against donating their biological materials, there are good ethical reasons to make this type of access
impossible or at least severely restricted. We also provide an ethical argument for the claim that, if a total ban on this
type of forensic access cannot be achieved, potential research subjects should be informed about the extent to which
this type of forensic access is possible.
[22] Does science need bioethicists? Ethics and science collaboration in biomedical research. Kerasidou A, Parker M.
Research ethics 2014; 10:214-226. Biomedical research is an increasingly multidisciplinary activity bringing together a
range of different academic fields and forms of expertise to investigate diseases that are increasingly understood to be
complex and multifactorial. Recently the discipline of ethics has been starting to find a place in large-scale biomedical
collaborations. In this article we draw from our experience of working with the Malaria Genomic Epidemiology Network
(MalariaGEN) and other research projects to reflect upon the integration of ethics into biomedical research. We examine
the way in which ethics input may be valuable to research, the forms it tends to take, and also the problems and
limitations of such collaborations.
[23] A widefield fluorescence microscope with a linear image sensor for image cytometry of biospecimens:
Considerations for image quality optimization. Hutcheson JA, Majid AA, Powless AJ, Muldoon TJ. The Review of
scientific instruments 2015; 86:093709. Linear image sensors have been widely used in numerous research and industry
applications to provide continuous imaging of moving objects. Here, we present a widefield fluorescence microscope
with a linear image sensor used to image translating objects for image cytometry. First, a calibration curve was
characterized for a custom microfluidic chamber over a span of volumetric pump rates. Image data were also acquired
using 15 mum fluorescent polystyrene spheres on a slide with a motorized translation stage in order to match linear
translation speed with line exposure periods to preserve the image aspect ratio. Aspect ratios were then calculated after
imaging to ensure quality control of image data. Fluorescent beads were imaged in suspension flowing through the
microfluidics chamber being pumped by a mechanical syringe pump at 16 mul min(-1) with a line exposure period of 150
mus. The line period was selected to acquire images of fluorescent beads with a 40 dB signal-to-background ratio. A
motorized translation stage was then used to transport conventional glass slides of stained cellular biospecimens. Whole
blood collected from healthy volunteers was stained with 0.02% (w/v) proflavine hemisulfate was imaged to highlight
leukocyte morphology with a 1.56 mm x 1.28 mm field of view (1540 ms total acquisition time). Oral squamous cells
were also collected from healthy volunteers and stained with 0.01% (w/v) proflavine hemisulfate to demonstrate
quantifiable subcellular features and an average nuclear to cytoplasmic ratio of 0.03 (n = 75), with a resolution of 0.31
mum pixels(-1).