The present invention relates to diagnostics, especially for analytes in the form of liquid droplets.
WO2016/122577 (Hewlett Packard) describes a microfluidic device with microfluidic channels.
JINHONG GUO: “Uric Acid Monitoring with a Smartphone as the Electrochemical Analyzer”, Analytical Chemistry. Vol. 88, no. 24, 20 Dec. 2016 pages 11986-11989, US ISSN: 0003-2700, DOI: 10.1021/acs.analchem.6b04345 describes a polypropylene film with screen-printed carbon electrodes.
The present invention is directed towards providing a portable diagnostic sensor device which is easy to use for small volume samples such as in droplet form, and/or which allows for rapid assay development, employing multiple connection and detection methods for versatility and increased accuracy.
Another objective is that such a device be suited to applications such as providing detection and quantification testing for beads, DNA, RNA, proteins, and similar analytes.
We describe a diagnostic sensor device comprising:
Because of the monolithic manufacture there are very few steps, merely the well-established semiconductor fabrication steps such as CMOS processing. There is no need for downstream handling and the device may be used immediately after dicing from a wafer.
The device may comprise a layer of hydrophobic material which is etched to form an exposed sensing region for each sensor. Preferably, the hydrophobic material comprises polyimide.
Preferably, the circuit includes converters and digital calibration circuits. Optionally, at least some of the converters and digital calibration circuits are located directly beneath the sensors.
The circuit may comprise capacitive sensors.
The device distal end may be configured to fit into a 12-pin USB connector socket or a 12-pin FFC socket, or for example the sensor device may be configured to mimic a flat flex cable in terms of dimensions.
The sensor regions may be configured to receive and hold sample droplets or beads with different concentrations.
The device may further comprising an interface having engagement pads configured to overlap and engage the pads of the integrated circuit, and the interface comprises contacts for engaging as a male component in a female component of a non-proprietary data and power transfer standard, and optionally the interface has chamfered leading edges. This would provide an assembly of a device which can fit into a non-proprietary socket but may use an interface or “interposer” if it is desired to have sufficient uses that might damage the pads.
We also describe a diagnostic sensor system comprising a sensor device of any embodiment and a host processor programmed to provide power to, and to receive data from, the sensor device via a non-proprietary interface, and to process said data to provide an output.
We also describe a method of manufacturing a sensor device of any embodiment, the method comprising fabricating a wafer with a plurality of semiconductor integrated circuits each forming a sensor device with said configuration, with said pads, with said sensors, and with said circuit, and dicing the wafer to provide the device. It will be appreciated that this is a very simple way of designing and manufacturing a device, requiring only a single fabrication process. There is no need for post-fabrication processes such as packaging and hence little scope for error or damage.
The wafer may be manufactured in an integrated CMOS process in which the pads are deposited and the sensors are formed, and in which the sensors comprise sensor electrodes formed from a top metal layer during fabrication.
Optionally, after completion of wafer processing, the wafer is back-ground to a desired thickness to provide said configuration,
The method may comprise polyimide deposition and etching.
Additional Statements
According to the invention, there is provided a diagnostic sensor device comprising a planar substrate having:
In one embodiment, the planar substrate is monolithic.
In one embodiment, the planar substrate comprises a layer of hydrophobic material formed on the semiconductor chip and which is etched to form an exposed sensing region on each sensor.
In one embodiment, the hydrophobic material comprises polyimide.
In one embodiment, the circuit includes converters and digital calibration circuits.
In one embodiment, at least some of the converters and digital calibration circuits are located directly beneath the sensors.
In one embodiment, the circuit comprises capacitive sensors.
In one embodiment, the planar substrate distal end is configured to fit into a 12-pin USB connector socket or a 12-pin FFC socket.
In one embodiment, the sensor is configured to mimic a flat flex cable in terms of dimensions.
In one embodiment, the sensor areas are configured to receive and hold sample droplets or beads with different concentrations.
In one embodiment, the device further comprises an interface having engagement pads configured to engage the pads with the planar substrate and the interface overlapping, and the interface comprises contacts for engaging as a male component in a female component of a non-proprietary data and power transfer standard, and optionally the interface has chamfered leading edges.
We also describe a diagnostic sensor system comprising a sensor device of any embodiment and a host processor programmed to receive data from said device via a non-proprietary interface and to process said data to provide an output.
We also describe a method of manufacturing a sensor device, the device comprising:
In one embodiment, the wafer is manufactured in an integrated CMOS process in which the pads are deposited and the sensors are formed, and in which the sensors comprise sensor electrodes formed from a top metal layer during fabrication.
In one embodiment, after completion of wafer processing, the wafer is back-ground to a desired thickness to provide said configuration,
The invention will be more clearly understood from the following description of some embodiments thereof, given by way of example only with reference to the accompanying drawings in which:—
A diagnostic sensor device 1 comprises a silicon planar integrated circuit having a CMOS multi-layer circuit body 2 having a distal end with exposed pads 3 and a proximal end 4 with capacitive sensor electrodes 5. The distal end is physically configured to fit into a power and data socket conforming to a non-proprietary standard, in this case Universal Serial Bus, USB. The proximal end 4 has three sensor regions 5 with capacitive sensor electrodes 5 for detection of an analyte. The multi-layer circuit 6 is alongside and underneath the sensor regions 5 and the contact pads 3. In other embodiments the circuit may be fully located beneath one of the electrodes or sensor regions.
The sensor device 1 is diced from a silicon wafer and it includes in an integrated manner the pads 3, the circuit body (2), the multi-layer circuit 6, and the sensor 5 components. These are monolithically integrated as a semiconductor IC (or “semiconductor chip”). There is no packaging, and the device 1 is planar, as it is diced from a semiconductor wafer in manufacture.
The sensor device 1 distal end has the configuration of a USB-C, being 6.5 mm wide, and having twelve pads 3 with a pad pitch of 0.5 mm, to exactly mimic the male-portion of a USB-C, which typically can be found as a protrusion in the motherboard PCB in laptops and phones, for example in the USB-C slot of the Samsung Galaxy S8 smartphone. The pads 3 are therefore configured to accurately engage the female portion of USB-C, which has 12-spring biased pins, making contact with the 12 pads on the sensor chip. This female part of USB-C is typically found at the end of a USB-C cable (as shown in
The proximal section 4 three sensor areas 5 are of 1 mm diameter, suitable for receiving a droplet of analyte to be tested. The device's circuit body 2 has a multi-layer circuit 6 linked with both the pads 3 and with the sensors 5 for sensor data processing. The multi-layer circuit 6 comprises CMOS converters, digital calibration circuits, and memory storage. The three capacitive sensors 5 measure and compare the analyte with positive and negative controls, and resolve to femto-Farad and atto-Farad resolution. The circuits may also extend underneath the sensors 5 and/or the pads 3 in a CMOS multi-layer arrangement.
Referring to
At completion of processing, the wafer is back-ground to a thickness of 0.4 mm for example, to provide a suitable thickness for the sensor device 1. The wafer is then placed on an adhesive film on a ring carrier, which is placed on a wafer-saw machine. This dices the wafer in both X and Y dimensions, leaving individual integrated circuit chips on the film. These can be lifted directly from the film to be ready for use as the devices 1.
Copper or Gold plating of aluminium pads may be employed on CMOS semiconductor processes, as a redistribution layer (RDL) to facilitate solder-bumping or flip-chip assembly. In another embodiment, the interconnect contact pads are plated with copper or gold. This thicker layer facilitates multiple-use insertion and testing.
The arrangement of the sensors and their regions may be chosen at design stage, before the integrated manufacturing process. It will be appreciated that the full sensor device is manufactured in a single process involving CMOS processing, and optionally polyimide deposition and etching. It is therefore monolithic.
In another embodiment, referring to
The interface 12 has land-patterns 16 laid out in a pattern matching the solder-bumps 15 in order to receive the solder balls during a flip-and-solder operation. The centre of
Therefore in this embodiment the sensor device 11 is suited to fit directly into a USB socket as for the sensor device 1, but it does not need to do so as the interface 20 is more suited to this function, particularly if multiple insertions are required. The interface 12 has the same width and depth as the sensor device 11 but is more suited to repeated insertion into a socket because it is of PCB material and because it has chamfers and leading tapered side edges 18 to allow easy and accurate insertion into the socket and mating of the twelve gold pads 14 to the twelve spring-loaded pins in connector 10.
In another embodiment, gold-studs form the electrical connections between the sensor device 11 and interposer 12.
Instead of FR4 PCB adaptor material, the sensor device may be attached to a transparent co-polymer adaptor, also configured to fit directly into a standard data and power socket. This facilitates further microfluidic assay integration.
In another embodiment, a sensor device 30 may be configured to fit into a 12-pin FFC socket 50 as shown in
Referring to
A major advantage of the invention is that the sensor device is a planar monolithic integrated circuit without any packaging such as plastics encapsulation nor any fluidic channels. It is manufactured in one process, namely the manufacture of an integrated circuit wafer, in one wafer fabrication facility, with one design and mask-set, with or without a polyimide or other insulation layer, with or without back-grinding to provide for different thicknesses, with or without RDL plating of pads, with or without solder bumps, and with wafers mounted on film and diced, prior to shipment. Upon receipt, the sensor devices are then immediately ready for use. Where many uses are envisaged an interface such as described may be used for inserting into the non-proprietary or standard socket.
The 6.5 mm chip width and 12 pads at 0.5 mm pitch is also particularly convenient, matching the dimensions of both the 12-pin USB-C and 12-pin FFC sockets.
Thus, the expensive upfront investment in one CMOS IC design, layout, and mask set can be leveraged and amortised over many wafer-fabrication options thicknesses, and end-user socket and connection options, facilitating rapid assay development and iteration.
The invention is not limited to the embodiments described but may be varied in construction and detail.
Number | Date | Country | Kind |
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17192159.6 | Sep 2017 | EP | regional |
Filing Document | Filing Date | Country | Kind |
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PCT/EP2018/074056 | 9/6/2018 | WO | 00 |