Lithium is the first-line treatment for bipolar disorder. However, the narrow therapeutic window of serum (s-)lithium is near its toxicity range, necessitating continuous monitoring of patients, a process involving regular hospital visits. On-demand home sampling could allow for more frequent testing, possibly resulting in safer patient outcomes, further dosage optimization, and increased compliance. This article presents a device that measures the s-lithium concentration from whole blood. The device consists of a single-use cartridge able to conduct on-chip serum filtration, volume-metering and an on-chip colorimetric assay. Spiked whole blood shows good linearity (Pearson's r = 0.96, R2 = 0.92), a limit-of-detection of 0.3 mmol L-1, and an average deviation of 0.05 mmol L-1 (+/- 6%) compared to atomic absorption spectroscopy. The on-chip colorimetric assay has shown to be a promising technique for measuring s-lithium concentration from whole blood and could allow patients to assess lithium levels at home and make the treatment available for new patient groups.

Patient-centric sampling strategies, where the patient performs self-sampling and ships the sample to a centralized laboratory for readout, are on the verge of widespread adaptation. However, the key to a successful patient-centric workflow is user-friendliness, with few noncritical user interactions, and simple, ideally biohazard-free shipment. Here, we present a capillary-driven microfluidic device designed to perform the critical biomarker capturing step of a multiplexed immunoassay at the time of sample collection. On-chip sample drying enables biohazard-free shipment and allows us to make use of advanced analytics of specialized laboratories that offer the needed analytical sensitivity, reliability, and affordability. Using C-Reactive Protein, MCP1, S100B, IGFBP1, and IL6 as model blood biomarkers, we demonstrate the multiplexing capability and applicability of the device to a patient-centric workflow. The presented quantification of a biomarker panel opens up new possibilities for e-doctor and e-health applications.

Rapid on-site evaluation (ROSE) increases the diagnostic accuracy of fine-needle aspiration (FNA) samples from cysts, a sack-like fluid-containing tissue that sometimes can be precancerous, but is highly dependent on the skills and availability of cytopathologists. We present a semiautomated sample preparation device for ROSE. The device consists of a smearing tool and a capillary-driven chamber that allow smearing and staining of an FNA sample in a single platform. Here, we show the capability of the device to prepare samples for ROSE, using a human pancreatic cancer cell line (PANC-1) and liver, lymph node, and thyroid FNA model samples. Using microfluidics, the device reduces the equipment needed in an operating room for FNA sample preparation, which may lead to a wider implementation of ROSE in healthcare centers.

Background: Performing complete blood counts (CBC) from patients´ homes could have atransformative impact on e-based healthcare. Blood microsampling and sample drying are enablingelements for patient-centric healthcare. The aim of this study is to investigate the potential of dry bloodsamples for image-based cell quantification of red and white blood cells. Methods: A manual samplepreparation method is developed and tested for image-based red and white blood cell counting. Resultsand Conclusion: Dry blood samples enable image-based cell counting of red and white blood cells with agood correlation to gold standard hematology analyzer data (avg. CV < 6.5%, R2 > 0.8), and resolve thebasic morphology of white blood cell nuclei. The presented proof-of-principle study is a first step towardpatient-centric CBCs.

Sample preparation is an integral part of bio-medical analysis routines, as it makes specimens of interest compatible with downstream instrumentation. Correct and proper sample preparation is of critical importance for reliable analysis results. However, conventional preparation procedures often entail numerous manual user interactions, which cause variations in sample quality and can lead to biased results. Microfluidics is a promising technology to address these problems since on-chip integration of sample preparation steps, such as volume metering, liquid handling, and sample fixation, can minimize critical user interactions. This thesis explores capillary-driven microfluidic devices for sample preparation of bio-medical specimens in patient-centric blood analysis workflows and laboratory environments. Patient-centric blood analysis, where patients take and send samples to a central laboratory for quality-assured readout, is an emerging field where capillary-driven microfluidic solutions can enable consistent sample preparation in remote locations. Blood plasma, the gold standard in blood analysis routines, is typically extracted by centrifugation, which is not readily available in remote settings. To address this limitation, we realized a microfluidic device for capillary-driven blood plasma separation from undiluted human whole blood. Based on this approach, we developed a device that generates a volume-defined dried plasma spot ready to be shipped to a laboratory for mass spectrometry. Using the same plasma separation approach, we developed a device that performs the critical analyte binding step of a multiplexed immunoassay at the time of sample collection. Sample drying and shipment to a laboratory then allow to make use of the unparalleled performance of highly specialized laboratory equipment. Along the same line of patientcentric workflows, we showed that specially treated dry blood samples enablered and white blood cell quantification with good correlation to gold standard hematology analyzer data. In addition, this thesis describes microfluidic devices that prepare samples in laboratory environments. We present microfluidic alternatives to manual procedures for the preparation of virus particles and proteins for transmission electron microscopy, and for the preparation of liquid biopsy samples for cytology investigations.

Provberedning är en kritisk del i biomedicinska analysrutiner för att göra prover kompatibla med instrument i analysens senare moment. Korrekt provberedning är kritiskt för att få pålitliga analysresultat. Konventionell provberedning innehåller dock ofta flera manuella steg, vilket orsakar variation i provkvalitet och kan leda till felaktiga resultat. Mikrofluidik är en lovande teknologi för att hantera dessa problem. Genom att integrera provberedningssteg som exempelvis volymmätning, vätskehantering och provfixering på ett mikrofluidiskt chip, kan manuell interaktion med provet minimeras. Den här avhandlingen utforskar kapillärdrivna mikrofluidiska chip för provberedning av biomedicinska prover för analys i både patientcentrerade arbetsflöden och labbmiljöer. Patientcentrerad blodanalys, där patienterna själva tar och skickar provet till ett centralt labb för kvalitetssäkrad avläsning, är ett framväxande fält där kapillärdrivna mikrofluidiska lösningar kan möjliggöra pålitlig provberedning även utanför labbet. Blodplasma är guldstandard i blodanalysrutineroch extraheras vanligtvis med centrifugering – en utrustning som sällan finns tillgängligt utanför en labbmiljö. För att adressera denna begränsning så utvecklade vi ett mikrofluidiskt chip för kapillärdriven blodplasma-separation från outspädda helblodsprover från människa. Baserat på denna teknik för blodplasma-separation utvecklade vi två olika chip. Det ena extraherar en specifik volym blodplasma som torkar in, och är därefter redo att transporteras till ett labb för masspektrometri. Det andra utför den kritiska analytbindningen i multiplexa immunanalyser under tiden som provet tas. Intorkning av vätskeprovet och efterföljande transport till ett labb möjliggör användandet av högspecialiserad labbutrustning. Vi visar även att en speciell behandling avtorkade blodprover gör det möjligt att kvantifiera röda och vita blodkroppar med god korrelation till guldstandard inom hematologi. Utöver detta beskriver den här avhandlingen mikrofluidiska chip som förbereder prover i labbmiljöer. Vi presenterar mikrofluidiska alternativ till manuella procedurer för beredning av viruspartiklar och proteiner för transmissionselektronmikroskopi och för beredningen av biopsiprover i vätskeform för cytologiska utvärderingar.

Rapid on-site evaluation (ROSE) significantly improves the diagnostic yield of fine needle aspiration (FNA) samples but critically depends on the skills and availability of cytopathologists. Here, we introduce a portable device for semi-automated sample preparation for ROSE. In a single platform, the device combines a smearing tool and a capillary-driven chamber for staining FNA samples. Using a human pancreatic cancer cell line (PANC-1) and liver, lymph node, and thyroid FNA model samples, we demonstrate the capability of the device to prepare samples for ROSE. By minimizing the equipment needed in the operating room, the device may simplify the performance of FNA sample preparation and lead to a wider implementation of ROSE.

On-chip immunoassays have great potential to accelerate point-of-care (POC) testing. However, most attempts require either impractical readout equipment or are outperformed by the sensitivity, reliability and affordability offered by centralized laboratories. Here, we present a capillary-driven microfluidic device that unites the best of two worlds: Bead-based analyte isolation at the POC, where analyte drying enables simple mail-based shipping, combined with the powerful capabilities of centralized laboratories. Using C-reactive protein (CRP) as model biomarker we demonstrate on-chip assay performance similar to conventional assays, with a LOD of 10 pg/ml and average CV of 9.7 % (48 microfluidic devices).

Transmission electron microscopy (TEM) allows for visualizing and analyzing viral particles and has become a vital tool for the development of vaccines and biopharmaceuticals. However, appropriate TEM sample preparation is typically done manually which introduces operator-based dependencies and can lead to unreliable results. Here, we present a capillary-driven microfluidic single-use device that prepares a TEM grid with minimal and non-critical user interaction. The user only initiates the sample preparation process, waits for about one minute and then collects the TEM grid, ready for imaging. Using Adeno-associated virus (AAV) particles as the sample and NanoVan (R) as the stain, we demonstrate microfluidic consistency and show that the sample preparation quality is sufficient for automated image analysis. We further demonstrate the versatility of the microfluidic device by preparing two protein complexes for TEM investigations using two different stain types. The presented TEM sample preparation concept could alleviate the problems associated with human inconsistency in manual preparation protocols and allow for non-specialists to prepare TEM samples.

Transmission electron microscopy (TEM) allows to directly visualize and characterize small biological particles, such as viruses, making it an indispensable tool for development of vaccines and pharmaceuticals. However, the manual TEM grid preparation protocol strongly depends on the skill of the operator and affects the preparation consistency. Here, we present a capillary-driven microfluidic device for negative stain TEM (nsTEM) grid preparation with minimal user interaction. The presented device could make TEM grid preparations more consistent and provide non-specialists access to biological TEM investigations.