Nanotechnology is helping create innovative physical systems for single-cell analysis. A number of bio-inspired solid-state devices have emerged in recent years that utilize micro and nanoscale features to interface cells and to detect molecular biomarkers. These provide rapid, label-free, and selective identification of diseased cells. The sensing and recognition of diseased cells when these are very few in numbers, especially in early stages of cancer, require nanoscale approaches that biomimic physiological conditions. Such engineered single-cell analysis approaches are providing new insights about cancer progression and can be important to tackle early cancer detection challenges. The biologically inspired nano-manufacturing frameworks can be extended to other investigations, especially where viscoelastic, mechanical and chemical behaviors can be used combinatorially to faithfully transduce important molecular and cellular anomalies to meaningful signals.  This talk will provide an overview on detection, isolation and sorting of diseased cells with nanotechnologies and microfluidics.

Translation of Research for MR Guided Focused Ultrasound Application for Moving Target Tumour Ablation in Abdominal Area: Project Trans-Fusimo

Minimally invasive surgeries are getting more popular due to their advantageous over traditional methods. Magnetic Resonance Guided Focused Ultrasound has been CE (Conformité Européene) marked, and Food & Drug Administration (FDA) approved for the treatment of uterine fibroids and the treatment of pain for bone metastasis within the last decades. However, to apply this technique for ablation of tumours in the abdominal area is more challenging due to the motion caused by breathing activity. The liver has limitations due to the ribcage as well. These challenges need to be resolved for this technique to be applied to the patients in clinics safely and reliably. The basic science to overcome these challenges were established in project FUSIMO by introducing tracking, motion compensation, and trans-costal beam steering techniques. With the established proof of concept, the next stage is the translation of research from science to the clinical applications. Due to the regulations, the evidence needs to be demonstrated before the clinical trials. For this reason, ISO 13485, quality management system is utilised.  System specs are defined and pre-clinical test protocols are designed to ensure conformance to the specs, the safety, the reliability and the repeatability of the system. Risk analysis are performed to mitigate the risk for animal trials. Assessment of efficacy is to be demonstrated in animal trials and clinical trials. Based on the successful results, CE mark approval will enable this technique to be utilised in clinics for a wider patient population efficient and reliably.  The pathway followed in this application might inspire other researchers in the field to conduct translation of research, which is normally known as valley of death due to limitations imposed by lack of funding and strict limitations of the regulations. So that the established science can help to serve to improve the welfare of the patients.

The application of nanotechnology in medicine is refered as nanomedicine, which is gaining importance and becoming promising espceially with advances in the development of novel nanomaterials.The novel nanomaterials, whose physicochemical properties differ from their larger counterparts due to their higher surface-to volume ratio, have become excellent candidates for biomedical applications.Their small size and larger surface areas make them readily interact with biomolecules in biological enviroments.By gaining acess to various sites of the body, nanoparticles provide the potential to detect and treat the disease.The aim of ‘nanomedicine’might be broadly defined the comphrensive monitoring, control, construction, repair,defense and improvement of biological systems, using engineered nanostructure ultimately to achive medical benefits. Among all nanomaterials, colloidal mesoporous silica particles have been extensively used in diverse biomedical applications (1)contrsat agents/optical labels that enable traceable imaging of targets, (2)carier to transport drug payload for threapeutic intervention and (3) carrier of biomolecular target ligands for targeted delivery.Within the mentioned platform, it is also desired to develop multifunctional silica nanoparticles which posses find-, fight- and follow –capabilities (3F funltionality) that make the nanoparticles feasable to be used as imaging probes for lession location (find), delivering the therapeutic agents to lession sites (fight) and also monitoring the development of threaphy (follow).All these tasks might be accomplished through careful and rational tuning of the physicochemical properties of silica nanoaparticles.In the representation of carried out studies, the methods to obtained tailor-made mesoporous silica nanoparticles provides them 3F multifunctionality will be described and simultaneously their usage in the field will be shown with the case studies. .

"Transrenal DNA" olarak adlandırılan, kaynağı çeşitli organlar olan düşük molekül ağırlıklı (LMW) DNA parçaları böbreklerden geçebilir ve idrarda birikebilir. Transrenal DNA, karaciğer, pankreas, kolon gibi uzak organlardan salınan, elde etmesi zor, “hücresiz DNA”lara erişmek için bir noninvaziv araç sağlar. Piezoelektrik plaka sensör (PEPS), 8 μm kalınlığında, yüksek piezoelektrik özelliğe sahip, kurşun magnezyum niobat-kurşun titanattan (PMN-PT) oluşan bir serbest tabakadır. Algılama için, analite özgü bir reseptör, PEPS yüzeyine sabitlenmiştir. Hedef analitin PEPS yüzeyindeki reseptöre bağlanması rezonans frekansının düşmesine sebep olur. Analitin yerinde, etiketsiz algılanması, PEPS'in rezonans frekansının takip edilmesi ile sağlanır.

Bu çalışmanın amacı, PEPS'I daha da geliştirerek, uzak organlardan kaynağını alan transrenal gen mutasyonlarının hızlı, etiketsiz, çoklu ve yüksek hassasiyette idrarda teşhis edilmesidir. Bu amaçla, hepatocellular karsinom (HCC) için bir risk faktörü olan hepatit B virüsünün (HBV) 1762T / 1764A çifte mutasyonu ve kolorektal karsinomların % 50'sinde (CRC) bulunan kodon 12'deki Kras nokta mutasyonu, model transrenal gen mutasyonları olarak seçilmiştir. Bu amacı gerçekleştirmek için, rezonans spektrumundaki gürültüyü azaltarak algılama rezonansının çözünürlüğünü artıran bir sinyal işleme algoritması geliştirilmiştir. Hedef DNA’nın izolasyonuna yada kopya sayısının artırılmasına duyulan gereksinimi ortadan kaldıracak, doğal olarak bulunan çift sarmallı hedef DNA’yı denşirebilecek, sıcaklık kontrollü kompartmanlar içeren bir akış sistemi uygulanmıştır. Sıcaklık, akış hız ve kilitli nükleik asit (LNA) kullanılarak, mutasyona uğramış DNA'yı yaban türü DNA’dan ayırt edebilecek teşhis özgülüğü artırılmıştır. Birden çok teşhisin eş zamanlı yapılabilmesini mümkün kılan bir system de geliştirilmiştir.

Sonuçlar, PEPS'in Kras noktasal mutasyonlarını idrarda 0.1 aM(60 kopya / ml) hassasiyet ve  1: 1000 mutant-yaban tip oranlı özgülükle, etiketsiz, DNA izolasyonu ve kopya sayısını artırmadan, doğrudan algılayabileceğini gösteriyor