A microfluidic cartridge for fast and accurate diagnosis of <i>Mycobacterium tuberculosis</i> infections on standard laboratory equipment

Homann, Ana R.; Niebling, Laura; Zehnle, S.; Beutler, Markus; Delamotte, Lubov; Rothmund, Marie-Christine; Czurratis, Daniel; Beller, Klaus-Dieter; Zengerle, Roland; Hoffmann, Harald; Paust, Nils

doi:10.1039/d1lc00035g

Cited by 30 publications

(25 citation statements)

References 19 publications

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“…In most LoaD systems, these valves retain the liquid during so-called laboratory unit operations ("LUOs"), such as metering and mixing, which are extensively covered in the literature [45,[50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69], and briefly in a subsequent section within the context of LSI. Furthermore, while essential ingredients for full-fledged LoaD applications, we refer to the numerous specialized publications regarding the many, primarily optical or electrochemical, techniques for downstream detection [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]70,71].…”

Section: Introductionmentioning

confidence: 99%

Design Optimization of Centrifugal Microfluidic “Lab-on-a-Disc” Systems towards Fluidic Larger-Scale Integration

Ducrée

2021

Applied Sciences

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Enhancing the degree of functional multiplexing while assuring operational reliability and manufacturability at competitive costs are crucial ingredients for enabling comprehensive sample-to-answer automation, e.g., for use in common, decentralized “Point-of-Care” or “Point-of-Use” scenarios. This paper demonstrates a model-based “digital twin” approach, which efficiently supports the algorithmic design optimization of exemplary centrifugo-pneumatic (CP) dissolvable-film (DF) siphon valves toward larger-scale integration (LSI) of well-established “Lab-on-a-Disc” (LoaD) systems. Obviously, the spatial footprint of the valves and their upstream laboratory unit operations (LUOs) have to fit, at a given radial position prescribed by its occurrence in the assay protocol, into the locally accessible disc space. At the same time, the retention rate of a rotationally actuated CP-DF siphon valve and, most challengingly, its band width related to unavoidable tolerances of experimental input parameters need to slot into a defined interval of the practically allowed frequency envelope. To accomplish particular design goals, a set of parametrized metrics is defined, which are to be met within their practical boundaries while (numerically) minimizing the band width in the frequency domain. While each LSI scenario needs to be addressed individually on the basis of the digital twin, a suite of qualitative design rules and instructive showcases structures are presented.

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Section: Introductionmentioning

confidence: 99%

Design Optimization of Centrifugal Microfluidic “Lab-on-a-Disc” Systems towards Fluidic Larger-Scale Integration

Ducrée

2021

Applied Sciences

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“…These LUOs are overwhelmingly processed in a batch-wise, rather than a continuous-flow fashion, by transiently sealing their fluidic exit with a normally-closed valve, thus intermittently stopping the flow while continuing rotation within certain boundaries, e.g., for vigorous agitation of the liquid sample. These centrifugal LUOs and their linked downstream detection techniques have been comprehensive reviewed elsewhere [24][25][26][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67].…”

Section: Introductionmentioning

confidence: 99%

Systematic Review of Centrifugal Valving Based on Digital Twin Modelling towards Highly Integrated Lab-on-a-Disc Systems

Ducrée¹

2021

Preprint

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Current, application-driven trends towards larger-scale integration (LSI) of microfluidic systems for comprehensive assay automation and multiplexing pose significant technological and economical challenges to developers. By virtue of their intrinsic capability for powerful sample preparation, centrifugal systems have attracted significant interest in academia and business since the early 1990s. This review models common, rotationally controlled valving schemes at the heart of such “Lab-on-a-Disc” (LoaD) platforms to predict critical spin rates and reliability of flow control mainly based on geometries, location and liquid volumes to be processed, and their experimental tolerances. In absence of larger-scale manufacturing facilities during product development, the method presented here facilitates the provision of efficient simulation tools for virtual prototyping and characterization to greatly expedite design optimization according to key performance metrics. This virtual in silico approach thus significantly accelerates, de-risks and lowers costs along the critical advancement from idea, fluidic testing, bioanalytical validation and scale-up to commercial mass manufacture.

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“…This paper introduces strategies to incorporate anti-counterfeit technologies into commercially already well-established centrifugal microfluidic platform. These "Lab-on-a-Disc" (LoaD) systems, which have been successfully developed in industry [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and academia [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] since the early 1990s, pursue a conceptually simple mechanism for the transport and conditioning of liquid samples and reagents in so-called laboratory unit operations (LUOs) through the artificial gravity field created by a conventional spindle motor [52][53][54][55][56][57][58][59][60][61][62][63][64]…”

Section: Introductionmentioning

confidence: 99%

Anti-Counterfeit Technologies for Microfluidic “Lab-on-a-Disc” Systems

Ducrée¹

2021

Preprint

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Non-genuine medical products, including diagnostic devices, have become a lucrative business for fraudsters, causing significant damage to revenues and reputation of companies, as well as posing a significant risk to the health of people and societies. Along a “digital twin” representing centrifugal microfluidic flow control on exemplary “Lab-on-a-Disc” (LoaD) systems, a novel, two-pronged strategy to safeguard miniaturized point-of-care devices by means of secret features and manufacturing challenges is outlined; such “hardware encryption” is flexibly programmed for each chip during production, and deciphered from a secure, local or online database at the time of use. This way, unlicensed copying may be efficiently deterred by an unfavourable economy-of-scale, even in absence of legal prosecution.

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A microfluidic cartridge for fast and accurate diagnosis of Mycobacterium tuberculosis infections on standard laboratory equipment

Abstract: We present a novel centrifugal microfluidic approach for fast and accurate Tuberculosis (TB) diagnosis based on the use of standard laboratory equipment. The herein presented workflow can directly be integrated...

Cited by 30 publications

References 19 publications

Design Optimization of Centrifugal Microfluidic “Lab-on-a-Disc” Systems towards Fluidic Larger-Scale Integration

Design Optimization of Centrifugal Microfluidic “Lab-on-a-Disc” Systems towards Fluidic Larger-Scale Integration

Systematic Review of Centrifugal Valving Based on Digital Twin Modelling towards Highly Integrated Lab-on-a-Disc Systems

Anti-Counterfeit Technologies for Microfluidic “Lab-on-a-Disc” Systems

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