From laboratory bench to benchmark: technology transfer in laboratory medicine

Background: Life Sciences research, enhancing the occurrence of innovation, is able to impact clinical decision-making, both at diagnosis and therapy. Indeed, starting from the knowledge of specific needs and of technical-scientific demands, researchers can conceive and experiment innovative solutions. Despite these strengths, transferring research to the market in Life Sciences shows considerable criticalities. The aim of this paper is to provide concrete evidences on the processes of technology transfer based on the exploitation of the results obtained by KronosDNAsrl, an academic spin-off focused on reproductive medicine. Methods: Different tools were used to evaluate the technical feasibility (validation of the results obtained with the prototype) and to manage the technology transfer process of One4Two®. Results: The different analyses we carried out showed the feasibility of the proposed solution. As a result, the One4Two® prototype has been developed and validated. Conclusions: Here, we provide a strength of evidences on how knowledge obtained by translational research on "bench" can be used to be transferred to the market on "benchmark" enabling innovation in Laboratory Medicine. In addition, the model described for One4Two® can be easily transferred to other products

Innovative technologies for diagnosis and screening of genetic diseases in antenatal age

The rapid progress of the technologies applied to laboratory diagnostics allows several diagnostic and screening options for the identification of genetic diseases and chromosomal alterations in the antenatal age. Couples at risk to have a child with a chromosomal or genetic illness (i.e., carriers of previously identified genetic alterations, a previous child with a genetic condition, and/or a positive family history) should receive personalized genetic counselling, preferably before the pregnancy. In this way, couples will be able to receive appropriate information about the best diagnostic option based on their personal and familial history. Taking into account that prenatal diagnostic options are rapidly changing with the emerging of more sensitive technologies and that, consequently, the offer for diagnostic tests in reproductive medicine is increased, in this review we discuss about the diagnostic indications for each test in antenatal age, such as preimplantation, invasive prenatal and non-invasive prenatal diagnosis (PND). In addition, sampling and the laboratory techniques are well represented. Rapid progress of modern high-throughput molecular technologies, largely based on next generation sequencing, has required clinical validation studies. The most representative studies were included in order to better characterize the technology used for each diagnostic test. Therefore, the combination of innovative diagnostic technologies with the increase in demand (also related to the increased age of both partners facing the first pregnancy) has contributed to the practice of antenatal diagnosis and non-invasive prenatal screening (NIPT)

The evolving role of genetic tests in reproductive medicine

Infertility is considered a major public health issue, and approximately 1 out of 6 people worldwide suffer from infertility during their reproductive lifespans. Thanks to technological advances, genetic tests are becoming increasingly relevant in reproductive medicine. More genetic tests are required to identify the cause of male and/or female infertility, identify carriers of inherited diseases and plan antenatal testing. Furthermore, genetic tests provide direction toward the most appropriate assisted reproductive techniques. Nevertheless, the use of molecular analysis in this field is still fragmented and cumbersome. The aim of this review is to highlight the conditions in which a genetic evaluation (counselling and testing) plays a role in improving the reproductive outcomes of infertile couples. We conducted a review of the literature, and starting from the observation of specific signs and symptoms, we describe the available molecular tests. To conceive a child, both partners' reproductive systems need to function in a precisely choreographed manner. Hence to treat infertility, it is key to assess both partners. Our results highlight the increasing importance of molecular testing in reproductive medicine

Facts, Challenges, Difficulties and Hopes in Single-Cell Biology: Physiopathological Studies

Single-cell approaches are being increasingly used to unravel the many diverse mechanisms underlying biological processes that characterize each cell irrespective of the influx of other cells even within the same tissue. Consequently, the interference of metabolites and nervous stimuli emanating from the circulatory or nervous system in a higher organism like man is avoided. However, while the single-cell approach yields a wealth of data about single-cell metabolism and internal regulatory mechanisms, information about interactions and interrelations among similar or dissimilar cells may remain obscure. Starting from these considerations, here we summarize, without attempting to be exhaustive, some areas in which we think single-cell biological studies could be effective in translational medicine and in other areas of applied sciences. In this short review we describe the facts, challenges and perspectives related to these issues

Microbiota and Human Reproduction: The Case of Male Infertility

The increasing interest in metagenomics is enhancing our knowledge regarding the composition and role of the microbiota in human physiology and pathology. Indeed, microbes have been reported to play a role in several diseases, including infertility. In particular, the male seminal microbiota has been suggested as an important factor able to influence couple’s health and pregnancy outcomes, as well as offspring health. Nevertheless, few studies have been carried out to date to deeper investigate semen microbiome origins and functions, and its correlations with the partner’s reproductive tract microbiome. Here, we report the state of the art regarding the male reproductive system microbiome and its alterations in infertility

Dissecting Intra-Tumor Heterogeneity by the Analysis of Copy Number Variations in Single Cells: The Neuroblastoma Case Study

Tumors often show intra-tumor heterogeneity because of genotypic differences between all the cells that compose it and that derive from it. Recent studies have shown significant aspects of neuroblastoma heterogeneity that may affect the diagnostic-therapeutic strategy. Therefore, we developed a laboratory protocol, based on the combination of the advanced dielectrophoresis-based array technology and next-generation sequencing to identify and sort single cells individually and carry out their copy number variants analysis. The aim was to evaluate the cellular heterogeneity, avoiding overestimation or underestimation errors, due to a bulk analysis of the sample. We tested the above-mentioned protocol on two neuroblastoma cell lines, SK-N-BE(2)-C and IMR-32. The presence of several gain or loss chromosomal regions, in both cell lines, shows a high heterogeneity of the copy number variants status of the single tumor cells, even if they belong to an immortalized cell line. This finding confirms that each cell can potentially accumulate different alterations that can modulate its behavior. The laboratory protocol proposed herein provides a tool able to identify prevalent behaviors, and at the same time highlights the presence of particular clusters that deviate from them. Finally, it could be applicable to many other types of cancer

The total testing process harmonization: the case study of SARS-CoV-2 serological tests

The total testing process harmonization is central to laboratory medicine, leading to the laboratory test's effectiveness. In this opinion paper the five phases of the TTP are analyzed, describing, and summarizing the critical issues that emerged in each phase of the TTP with the SARS-CoV-2 serological tests that have affected their effectiveness. Testing and screening the population was essential for defining seropositivity and, thus, driving public health policies in the management of the COVID-19 pandemic. However, the many differences in terminology, the unit of measurement, reference ranges and parameters for interpreting results make analytical results difficult to compare, leading to the general confusion that affects or completely precludes the comparability of data. Starting from these considerations related to SARS-CoV-2 serological tests, through interdisciplinary work, the authors have highlighted the most critical points and formulated proposals to make total testing process harmonization effective, positively impacting the diagnostic effectiveness of laboratory tests

Congenital Diarrheal Disorders: An Updated Diagnostic Approach

Congenital diarrheal disorders (CDDs) are a group of inherited enteropathies with a typical onset early in the life. Infants with these disorders have frequently chronic diarrhea of sufficient severity to require parenteral nutrition. For most CDDs the disease-gene is known and molecular analysis may contribute to an unequivocal diagnosis. We review CDDs on the basis of the genetic defect, focusing on the significant contribution of molecular analysis in the complex, multistep diagnostic work-up