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We present a substantially improved design and functionality of a centrifugo‐magnetophoretic platform which integrates direct immunoseparation and cost‐efficient, bright‐field detection of cancer cells in whole blood. All liquid handling takes place in a disposable cartridge with geometry akin to a conventional compact disc (CD). The instrumentation required to process such a “lab‐on‐a‐disc” cartridge can be as simple and cost‐efficient as the rotor on a common optical disc drive. In a first step, target cells in a blood sample are specifically bound to paramagnetic microbeads. The sample is then placed into the disc cartridge and spun. In the second step, magnetically tagged target cells are separated by a co‐rotating, essentially lateral magnetic field from the background population of abundant blood cells, and also from unbound magnetic beads. A stream of target cells centrifugally sediments through a stagnant liquid phase into a designated detection chamber. The continuous, multiforce immunoseparation proceeds very gently, i.e. the mechanical and hydrodynamic stress to the target cells is minimized to mitigate the risk of cell loss by collective entrapment in the background cells or vigorous snapping against a wall. We successfully demonstrate the extraction of MCF7 cancer cells at concentrations as low as 1 target cell per μl from a background of whole blood, with capture efficiencies of up to 88%. Its short time‐to‐answer is a notable characteristic of this system, with 10% of target cells collected in the first minute after their loading to the system and the remainder captured within the following 10 min. All the above‐mentioned factors synergetically combine to leverage the development of a prospective point‐of‐care device for CTC detection.

Here we present a low cost, 3D printed optical reader which is compatible with a disposable, finger actuated chip which can be used for rapid CD4+ enumeration. This portable and widely autonomous device provides the next step in a workflow which can meet the WHO ASSURED requirements for assessment of HIV status in resource-poor settings. The reader is composed of 3D printed parts where the microfluidic chip can be moved along the optical axis of the objective lens for focusing using a screw adapted from a masonry bolt. Performance of the reader shows good agreement with measurements made using a conventional inverted microscope.

The suitability of the centrifugal “lab-on-a-disc” (LoaD) platform for point-of-use / point-of-care deployment, where ruggedness, portability, rapid turn-around times and ease-of-use are key, has resulted in increased interest from the academic community over the last decade. Recently, a new, so-called event-triggered valving paradigm was introduced which circumvented a number of the limitations of commonly used, rotationally actuated valves and complex instrument-controlled valving. In the dissolvable-film based event-triggered approach, it is the liquid movement about a disc which actuates a valve; thus enabling the concatenating of a number of liquid handling operations into an automated cascade. Functioning broadly independent of spin rate, the number of discrete valving operations is only limited by the available disc real-estate. In this work we present this valving paradigm to control a network of discrete Laboratory Unit Operations (LUOs) which, with experienced design, can be integrated together to implement complex fluidic assays. We describe how these valves can be configured, using Boolean-like network relationships, to implement LUOs such as sequential washing steps. We also describe how these valves can be configured to enable metering, mixing and selective routing of liquid flows. Finally, we describe how these valves can be configured to provide accurate temporal control of LUOs; thus providing an entire suite of process control technology which can be used to enable many bio-assays.

Rotational microfluidic platforms have attracted swiftly growing interest over the last decade due to their suitability for integration and automation of sample preparation and detection. Valving is of pivotal importance on these compact “Lab-on-a-Disc” (LoaD) platforms as all liquids are exposed to the same centrifugal field. A number of valving technologies have been developed to coordinate timing of serial and / or parallel multi-step / multi-liquid assay protocols comprising of laboratory unit opera-tions (LUOs) such as the release, metering and mixing of sample and reagents. So far these valving techniques could be broadly categorised into rotationally controlled or externally actuated schemes. Only recently a new, “event-triggered” flow control has been introduced. In this approach, a valve is opened upon arrival of a liquid at a defined destination on the disc; this innovative mechanism for the first time permits the cascading of LUOs independent of the spin rate. In one technology, dissolvable films (DFs) are configured with a pneumatic chamber to offer function akin to an electrical relay. Dissolving one DF, termed the control film (CF), results in the release of liquid at a distal location through a so-called load film (LF). In this paper, a new method for temporal control of actuating DF-based, event-triggered CFs which are serially aligned at defined distances along a paper strip is introduced. Liquids are transported through the paper strip at a given velocity, thus setting well-defined intervals between subsequent LUOs, e.g. incubation steps. As a proof-of-concept, we present a disc with inte-grated metering and mixing which can perform a prototypical, 4-fold serial dilution; a common function in bioanalytical protocols. Imbibition of the paper strip sequentially opens five valves for serial dilution and mixing. To illustrate an unprecedented level of on-disc automation, this is followed by a branched cascade of 17 event-triggered valves (for a total of 22 liquid handling steps) which completes the serial dilution protocol.

Even though an agreed phenotypic definition of circulating tumor cells (CTCs) remains elusive in the literature, many current detection technologies isolate candidate cells based on molecular recognition of cellular epitopes that may not accurately predict CTC load. Rather than using such an epitope specific “positive-capture” strategy, we present a chip-based, centrifugal microfluidic platform integrating “negative-capture” magnetophoretic removal of normal white blood cells (WBCs) from a sample and subsequent, array-based enumeration of individualized, (untagged) abnormal cells. We compared the numerical recovery of cells on the array with the status of the donor patient, showing that the chip can has the potential to indicate the oncogenic severity of the blood donor.

The inherent centrifugation capability of the so-called ‘Lab-on-a-Disc’ (LoaD) platforms is widely used for blood processing during sample preparation. Here we introduce a valving technique which ena-bles rotational control of paper wetting to actuate dissolvable film (DF) valves. This mechanism is applied to the separation of whole blood into its chief constituents; plasma, leukocytes and erythrocytes.

In this paper we present a method of buoyancy-driven centripetal pumping utilizing a heavy, water-immiscible liquid to displace an aqueous sample radially inwards against the prevailing centrifugal force. Using formerly introduced dissolvable-film valving, we demonstrate metering and bidirectional periodical pumping of a single sample in the radial direction. We then show integrated sample discretisation, meter-ing and buoyancy-driven inward pumping in a microfluidic structure designed towards multi-parameter bioassays. This structure permits centrifugation of sample on the periphery of a disc (where the centrifugal field p) and proves a high degree of metering accuracy better than 1.2%

Isolation of individual cells from a bulk sample is vital in cell based diagnostics. Previous work has established the ability to arrange target cells into ordered arrays, using physical barriers such as micropillars and cups [1]. We here present a magnetic separation device that allows the tagged cells of interest to align into a highly ordered array where they are selected based on both immuno-markers and size. But, unlike the physical barrier methods, our device is able to trap the cells using an only 160-nm thin film of permalloy (80% Nickel, 20% Iron) micropatterned on the base of the chamber (Fig. 1). Maxima of the magnetic field arise in the vicinity of the sharp edges of these localized micro-spots (Fig. 2), thereby creating potential wells to localize paramagnetic bioparticles such as tagged cells or beads during analysis or successive washing steps (Fig. 3). Compared to a complex network of physical barriers, the trapped cells can simply be released by turning off the external magnet, allowing for further downstream analysis or removal to waste.

Due to the pervasiveness of HIV infections in developing countries there exists a need for a low-cost, user-friendly point-of-care device which can be used to monitor the concentration of T-lymphocytes in the patient’s blood expressing the CD4+ epitope. As a first step towards developing a microfluidic “lab-on-a-disc” platform with this aim we present the concentration of white blood cells from whole blood using a density medium in conjunction with centrifugo-pneumatic siphon valves [1]. Two such valves are actuated simultaneously, removing the bulk of plasma through the upper valve and the bulk of WBCs through the lower valve while leaving the vast majority of red blood cells in the centrifugal chamber.