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

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

COVIDIAGNOSTIX : health technology assessment of serological tests for SARS-CoV-2 infection.

Abstract Objective In vitro diagnostic tests for SARS-COV-2, also known as serological tests, have rapidly spread. However, to date, mostly single-center technical and diagnostic performance's assessments have been carried out without an intralaboratory validation process and a health technology assessment (HTA) systematic approach. Therefore, the rapid HTA for evaluating antibody tests for SARS-COV-2 was applied. Methods The use of rapid HTA is an opportunity to test innovative technology. Unlike traditional HTA (which evaluates the benefits of new technologies after being tested in clinical trials or have been applied in practice for some time), the rapid HTA is performed during the early stages of developing new technology. A multidisciplinary team conducted the rapid HTA following the HTA Core Model® (version 3.0) developed by the European Network for Health Technology Assessment. Results The three methodological and analytical steps used in the HTA applied to the evaluation of antibody tests for SARS-COV-2 are reported: the selection of the tests to be evaluated; the research and collection of information to support the adoption and appropriateness of the technology; and the preparation of the final reports and their dissemination. Finally, the rapid HTA of serological tests for SARS-CoV-2 is summarized in a report that allows its dissemination and communication. Conclusions The rapid-HTA evaluation method, in addition to highlighting the characteristics that differentiate the tests from each other, guarantees a timely and appropriate evaluation, becoming a tool to create a direct link between science and health management

Complex chromosome rearrangements related 15q14 microdeletion plays a relevant role in phenotype expression and delineates a novel recurrent syndrome

Complex chromosome rearrangements are constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints. These are rarely seen in the general population but their frequency should be much higher due to balanced states with no phenotypic presentation. These abnormalities preferentially occur de novo during spermatogenesis and are transmitted in families through oogenesis