# Technique Evolutions for Microorganism Detection in Complex Samples: A Review
###### Abstract  
Rapid detection of microorganisms is a major challenge in the medical and industrial sectors. In a pharmaceutical laboratory, contamination of medical products may lead to severe health risks for patients, such as sepsis. In the specific case of advanced therapy medicinal products, contamination must be detected as early as possible to avoid late production stop and unnecessary costs. Unfortunately, the conventional methods used to detect microorganisms are based on time-consuming and labor-intensive approaches. Therefore, it is important to find new tools to detect microorganisms in a shorter time frame. This review sums up the current methods and represents the evolution in techniques for microorganism detection. First, there is a focus on promising ligands, such as aptamers and antimicrobial peptides, cheaper to produce and with a broader spectrum of detection. Then, we describe methods achieving low limits of detection, thanks to Raman spectroscopy or precise handling of samples through microfluidics devices. The last part is dedicated to techniques in real-time, such as surface plasmon resonance, preventing the risk of contamination. Detection of pathogens in complex biological fluids remains a scientific challenge, and this review points toward important areas for future research.  
Improvements in the detection of microorganisms are needed in medical and pharmaceutical domains [4; 5; 6]. Advanced therapy medicinal products such as gene therapy, cell therapy, and tissue engineering, constitute new medical important advances, specifically concerning the manipulation of living structures and reconstruction of the human body. Tissue engineering, sometimes referred to as regenerative medicine, includes applications that repair or replace, partially or completely, tissues (bone, skin, and muscle). Nevertheless, these therapies can increase microbial transmission risks to recipients, usually by bacteria but also yeasts and fungi. Cell products must be controlled during their production for microbial contamination as it can lead to life-threatening complications during transplantation, such as bacteremia causing septic shock. However, conventional tools are often bulky, expensive, and require several days to analyze a set of culture. These disadvantages are mainly related to the fact that these methods are mostly based on microbial growth [7]. These long response times are a real problem and have potentially fatal consequences. Therefore, the interest of developing new rapid and efficient tools for the detection of pathogens is increasingly important for pharmaceutical industries and regulatory agencies.  
The economic and health issues require reducing the detection delay to a few hours or even minutes, while having portable devices (easily transportable). However, it is difficult to combine sensitivity, cost-effectiveness, high selectivity, and simplicity in a portable and compact device. As a result, there is an increasing interest to produce and apply real-time detection devices with a high sensitivity but a rather low specificity allowing the detection of a wide panel of microorganisms. Given the large number of possible applications, this challenging task has drawn the interest of researchers [8]. In recent years, many articles have reported on the design and implementation of elaborate microbiological protocols [1; 3; 8; 9; 10] trying to provide more accurate, faster, analytic-specific, and robust results. Here, we conducted a literature review of technologies currently being developed for rapid pathogen detection in biological samples.