AU2018100116A4 - Apparatus and Method For Handling of Liquid Samples For Assays - Google Patents

Abstract

The present disclosure relates to an apparatus and a method for handling of liquid samples for assays. The apparatus and method comprises a set of microtiter substrates, each microtiter substrate comprising an array of sampling regions for carrying the liquid samples; and a rigid base comprising opposing first and second surfaces, and an array of holes extending through the first and second surfaces, the rigid base configured for mating and removing one microtiter substrate to the first surface, wherein each hole is wider than each sampling region, and the array of holes and the array of sampling regions are in an identical predetermined arrangement, such that one sampling region corresponds to one hole; and wherein when one microtiter substrate is mated to the first surface of the rigid base: each sampling region of the mated microtiter substrate resides within the corresponding hole of the rigid base when viewing from the second surface; the sampling regions are accessible, enabling introduction of the liquid samples to the sampling regions; and the sampling regions are configured for carrying the liquid samples within the corresponding holes and without physical contact with the rigid base in preparation for the assays of the liquid samples.

Description

APPARATUS AND METHOD FOR HANDLING OF LIQUID SAMPLES FOR

ASSAYS

Background

In a chemical or biological laboratory or setting, it is often necessary to perform analytical and/or experimental assays or procedures on a number of analyte samples or specimens, typically in the liquid form. Some objectives of these assays include determining the reaction of different samples against one or more reagents, such as labelled probes. The samples need to be handled and contained on an instrument or tool in order to perform tasks as part of the assays or procedures. Some common tasks that need to be performed on each sample include transfers (e.g. aspiration and dispensing), mixing, and stirring, as well as reading the results of each assay.

One common instrument or tool to contain the liquid samples is a microtiter plate or microplate. Each of these microplates is a monolithic substrate with multiple wells that are made according to the specifications recommended by the Society for Laboratory Automation and Screening (SLAS), which is a merger between the Society for Biomolecular Sciences (SBS) and the Association for Laboratory Automation (ALA). The SLAS sets out standards for these microplates which are known as ANSI/SLAS standards. A microplate typically has 6, 24, 96, 384, or 1536 wells for containing the liquid samples, wherein the wells are arranged in a 3:2 rectangular matrix. One of the more common types of microplates for use in experimental assays and procedures is the 96-well microplate.

These microplates are preferred for use with liquid samples for assays because they allow processes to be conducted in a highly parallel manner, which translates to high throughput. In addition, a large number of equipment has been built around the use of microplates. Microplates are typically made from thermoplastic polymers, and can be used as is, or with subsequent biochemical or irradiation treatment of the wells, such as to functionalize the microplate for specific applications (e.g. adhesion or removal of cells, proteins, and/or lipids therefrom). Biochemical functionalization typically involves dispensing predetermined liquids on the microplate, heating the microplate at specific temperatures in an incubator over certain periods of time, before they are discarded subsequently. This normally requires a few repetitive cycles before the whole process is completed.

As many microplates are typically used at any one time in the laboratory, there may be a problem of mixing up the microplates if they are not properly identified. In a highly automated environment, barcodes or radio frequency identification (RFID) tags can be attached to microplates, from which electronic readers can be used to distinguish and identify the microplates. There are also other forms of electronic automatic identification and data capture (AIDC) technologies which can be utilized. In a nonautomated or manual environment, microplates are often marked with an ink pen for identification. Unlike the use of electronic methods, it is difficult to incorporate time/date stamp and other data related to the microplates and/or liquid samples contained therein in this manner, due to the limited space on the microplate to do so. Another problem is that the markings on the microplates need to be changed when the liquid samples are replaced.

After using the microplates for assays, the microplates must be washed in order to be reused. Otherwise, they are discarded. Microplate washers can be configured to provide various effects from the washing thereof. For example, washers can provide for (i) removal of enzyme-linked immunosorbent assay (ELISA), protein, and/or antibody for improved consistency and reliability; (ii) gentle cleaning cell-based assays with adherent or weakly adherent cells; (iii) vacuum filtration to waste for polymerase chain reaction (PCR) clean up after deoxyribonucleic acid (DNA) amplification; or (iv) magnetic bead separation (MBS). The type of liquid samples that has been placed in the wells of the microplates must be properly identified before washers can be properly applied on them. Different types or configurations of the washers are suited for different liquid samples. The washers also need to be serviced and supplied with the right chemicals and detergents in order for microplates to be cleaned effectively for reuse.

When the microplates cannot be reused and are to be discarded, they cannot be disposed as general waste by default because of the residual chemicals therein. Depending on the liquid samples that had been placed in the microplates, they may need to be disposed as medical, biohazardous, or radioactive waste. This presents a problem in that the liquid samples must be properly identified in order to know how to dispose the microplates. It may also lead to wastage of microplates if they are frequently discarded instead of being reused, possibly due to additional trouble of washing the microplates.

United States Patent 6,485,690 discloses a multi-layered microplate structure for handling liquid samples for chemical synthesis and biological assays and/or processing. The microplate structure allows for multiple layers of liquid samples to be analyzed, thereby providing for high throughput. United States Patent 7,138,270 discloses an assay device having a plurality of wells, similar to a microplate. None of US 6,485,690 and US 7,138,270 discloses any form of labelling or identification of the microplate. Practitioners and users of the microplates can become confused as to which microplate contains what chemicals. This could further lead to hazardous situations when the wrong washing agents are used to wash the microplates for reuse. Although the microplates can be manually identified, this can be time-consuming and inefficient. United States Patent 7,666,355 discloses a barcode driven and automated microplate for performing assays. Barcodes are labelled on the microplates for identification thereof. However, the barcodes are for identifying the number of microplates rather than to provide more comprehensive information regarding the microplates and the contents of the samples contained therein.

Therefore, in order to address or alleviate at least one of the aforementioned problems and/or disadvantages, there is a need to provide an apparatus and method for handling of liquid samples for assays, in which there is at least one or some improved features over the prior art.

Summary

According to a first aspect of the present disclosure, there is an apparatus for handling of liquid samples for assays. The apparatus comprises a set of microtiter substrates, each microtiter substrate comprising an array of sampling regions for carrying the liquid samples; and a rigid base comprising opposing first and second surfaces, and an array of holes extending through the first and second surfaces, the rigid base configured to couple and decouple one microtiter substrate to the first surface, wherein each hole is wider than each sampling region, and the array of holes and the array of sampling regions are in an identical predetermined arrangement, such that one sampling region corresponds to one hole; and wherein when one microtiter substrate is mated to the first surface of the rigid base: each sampling region of the mated microtiter substrate resides within the corresponding hole of the rigid base; the sampling regions are accessible, enabling introduction of the liquid samples to the sampling regions; and the sampling regions are configured for carrying the liquid samples within the corresponding holes and without physical contact with the rigid base in preparation for the assays of the liquid samples.

According to a second aspect of the present disclosure, there is a method for handling of liquid samples for assays. The method comprises: providing a rigid base comprising opposing first and second surfaces, and an array of holes extending through the first and second surfaces; providing a set of microtiter substrates, each microtiter substrate comprising an array of sampling regions for carrying the liquid samples, wherein each hole is wider than each sampling region, and wherein the array of holes and the array of sampling regions are in an identical predetermined arrangement, such that one sampling region corresponds to one hole; retrieving one microtiter substrate from the set of microtiter substrates; mating the microtiter substrate to the first surface of the rigid base; accessing the sampling regions through the corresponding holes, wherein each sampling region of the mated microtiter substrate resides within the corresponding hole of the rigid base; and introducing the liquid samples to the sampling regions of the mated microtiter substrate, wherein the sampling regions are configured for carrying the liquid samples within the corresponding holes and without physical contact with the rigid base in preparation for the assays of the liquid samples.

An advantage of the present disclosure is that multiple batches of liquid samples can be contained in different microtiter substrates and analysed under different iterations of the assays. The apparatus provides a rigid base for use with disposable microtiter substrates. As the liquid samples do not contact the rigid base, no washing is required for the rigid base. There is also no contamination of the liquid samples.

An apparatus and method for handling of liquid samples for assays according to the present disclosure is thus disclosed hereinabove. Various features, aspects, and advantages of the present disclosure will become more apparent from the following detailed description of the embodiments of the present disclosure, by way of nonlimiting examples only, along with the accompanying drawings in which like numerals represent like components.

Detailed Description

In the present disclosure, depiction of a given element or consideration or use of a particular element number in a particular FIG. or a reference thereto in corresponding descriptive material can encompass the same, an equivalent, or an analogous element or element number identified in another FIG. or descriptive material associated therewith. The use of 7” in a FIG. or associated text is understood to mean “and/or” unless otherwise indicated. The recitation of a particular numerical value or value range herein is understood to include or be a recitation of an approximate numerical value or value range, for instance, within +/- 20%, +/-15%, +/-10%, +/- 5%, or +/- 0%. With respect to recitations herein directed to dimensional or numerical comparisons or equivalence, reference to the terms “generally,” “approximately,” or “substantially” is understood as falling within +/- 20%, +/- 15%, +/- 10%, +/- 5%, or +/- 0% of a representative / example comparison, or a specified or target value or value range; and reference to the term “essentially” is understood as falling within +/-10%, +/- 5%, +/- 2%, +/- 1%, or +/- 0% of a representative / example comparison, or a specified or target value or value range.

As used herein, the term “set” corresponds to or is defined as a non-empty finite organization of elements that mathematically exhibits a cardinality of at least 1 (i.e., a set as defined herein can correspond to a unit, singlet, or single element set, or a multiple element set), in accordance with known mathematical definitions (for instance, in a manner corresponding to that described in An Introduction to Mathematical Reasoning: Numbers, Sets, and Functions, “Chapter 11: Properties of Finite Sets” (e.g. as indicated on p. 140), by Peter J. Eccles, Cambridge University Press (1998)). In general, an element of a set can include or be a system, an apparatus, a device, a structure, an object, a process, a physical parameter, or a value depending upon the type of set under consideration.

For purposes of brevity and clarity, descriptions of embodiments of the present disclosure are directed to an apparatus and method for handling of liquid samples for assays, in accordance with the drawings in FIG. 1 to FIG. 9. While aspects of the present disclosure will be described in conjunction with the embodiments provided herein, it will be understood that they are not intended to limit the present disclosure to these embodiments. On the contrary, the present disclosure is intended to cover alternatives, modifications and equivalents to the embodiments described herein, which are included within the scope of the present disclosure as defined by the appended claims. Furthermore, in the following detailed description, specific details are set forth in order to provide a thorough understanding of the present disclosure. However, it will be recognized by an individual having ordinary skill in the art, i.e. a skilled person, that the present disclosure may be practiced without specific details, and/or with multiple details arising from combinations of aspects of particular embodiments. In a number of instances, well-known systems, methods, procedures, and components have not been described in detail as not to unnecessarily obscure aspects of the embodiments of the present disclosure.

In representative or exemplary embodiments of the present disclosure, an apparatus 20 for handling of liquid samples for assays, as well as a method for handling of liquid samples for assays, is described hereinafter. Such assays include, but are not limited to, chemical and/or biological assays and/or procedures on liquid analyte samples or specimens.

The apparatus 20 comprises a set of microtiter substrates 100, each microtiter substrate 100 comprising an array of sampling regions 102 for carrying the liquid samples. A representative embodiment of a microtiter substrate 100 is shown in FIG. 1. Specifically, the microtiter substrate 100 shown in FIG. 1 has 96 sampling regions 102 arranged in a 3:2 rectangular matrix, similar to a 96-well microplate. Alternatively, the number of sampling regions 102 on each microtiter substrate 100 can vary, such as 6, 24, 384, or 1536, as specified according to ANSI/SLAS standards.

Each rectangular microtiter substrate 100 is made of a pliable and/or flexible material, such as a thermoplastic polymer. The array of sampling regions 102 is arranged such that each sampling region 102 is directly in contact with the liquid samples residing thereon or therein. The microtiter substrate 100 can be fully transparent or opaque or partially translucent, such optical properties depending on the process and sensing mode applied thereon. For example, black opaque, white opaque, and transparent properties are more suited for fluorescence, chemiluminescence, and absorbance sensing, respectively.

In the array of 96 sampling regions 102 in the microtiter substrate 100 as shown in FIG. 1, the centre-to-centre distances between the sampling regions 102 is the same as that that prescribed by the SLAS for 96-well microplates. Although each sampling region 102 is shown to be circular in shape, they can be of any other geometrical shape. Each sampling region 102 is configurable using a variety of methods to retain the liquid samples thereon or therein. Such methods make use of known laws of physics that liquid bodies are retained better if there are sharp, jagged, or sudden edges. FIG. 2 illustrates various examples of configurations of a sampling region 102 - (a) a sampling region 102a on a microtiter substrate 100a has its outer rim 104a scratched or scribed onto the microtiter substrate 100; (b) a sampling region 102b on a microtiter substrate 100b has its outer rim 104b punched out to protrude from the microtiter substrate 100; (c) a sampling region 102c on a microtiter substrate 100c is debossed to form a shallow well with an edge 104c and a flat bottom on the microtiter substrate 100; (d) a sampling region 102d on a microtiter substrate 100d is debossed to form a shallow well with an edge 104d and a rounded bottom on the microtiter substrate 100; and (e) a sampling region 102e on a microtiter substrate 100e is embossed to similarly form a shallow well with an edge 104e and a flat inner surface on the microtiter substrate 100.

Alternatively, instead of deforming the microtiter substrate 100 as with the aforementioned methods, a hydrophobic material or substance 104f can be deposited by methods, such as coating, around each sampling region 102f of a microtiter substrate 10Of. The hydrophobic material or substance 104f covers all areas other than the sampling regions 102f on the microtiter substrate 10Of. In this way, the edge of each sampling region 102f is constituted more by the sudden transition from hydrophilic (liquid attracting) to hydrophobic (liquid repelling) surfaces or regions. The various configurations of the sampling regions 102 of the microtiter substrate 100 described above thus facilitate or improve the retention of liquid samples thereon or therein.

Yet alternatively, it may not be necessary to modify the microtiter substrate 100, particularly around the sampling regions 102, in any manner to facilitate or improve the retention of the liquid samples. Referring to the microtiter substrate 100g shown in FIG. 2, when the liquid sample that is placed on a sampling region 102g is small enough in volume, e.g. liquid sample 22 as shown, surface tension dominates and causes the liquid sample 22 to assume a semi-spherical shape. The liquid sample 22 is held in this shape and position at the sampling region 102g because of the extra pinning provided at the solid-liquid-gas phases. Due to this strong pinning behaviour, it is possible to even invert the microtiter substrate 100g without the liquid sample 22 falling off from the effect of gravity.

The pliable nature of the microtiter substrate 100 enables it to bend resiliently when a force is applied thereto, and to revert to its original state when the force is released. FIG. 3 illustrates that, in the presence of a sidelong compressive force 106, the microtiter substrate 100 can resiliently bend without buckling or kinking. In one embodiment, the bent radius 108 can go down to 100 millimetres. Once the compressive force 106 is released, the microtiter substrate 100 reverts to its original shape with minimal distortion.

Each microtiter substrate 100 can be made of a polymer sheet with a thickness of 0.05 to 0.3 millimetres. The microtiter substrate 100 may be treated with various chemicals or irradiation (e.g. ultraviolet radiation) to make it more effective in certain applications (e.g. adhesion or repulsion of cells in the liquid sample from the surface). FIG. 4 shows that the microtiter substrate 100 can have a protective film or coating 110 on an upper surface thereof. Alternatively or additionally, the microtiter substrate 100 can have the protective film or coating 110 on the lower surface thereof. The protective film or coating 110 prevents scratches from forming on, oil from staining, dust from accumulating on, and/or improving the light reflectivity of, at least one of the upper and lower surfaces of the microtiter substrate 100.

Due to its pliable nature, the microtiter substrate 100 requires attachment to a rigid body in order to effectively perform assays on the liquid samples contained in the sampling regions 102. The apparatus 20 comprises a rigid base 200, as shown in a representative embodiment with reference to FIG. 5A and FIG. 5B. The rigid base 200 is a structural body that provides sufficient rigidity to the microtiter substrate 100 when it is attached thereto, thereby overcoming the pliability of the microtiter substrate 100. The rigid base 200 comprises first and second surfaces opposing to each other. In some embodiments, the first surface is the upper surface 202 and the second surface is the lower surface 204. In some other embodiments such as the representative embodiment, the second surface is the upper surface 202 and the first surface is the lower surface 204. The rigid base 200 further comprises an array of holes 206 extending through the upper surface 202 and the lower surface 204. In the representative embodiment, the rigid base 200 is rectangular in shape that matches with or corresponds to the shape of the microtiter substrate 100. The dimensions of the rigid 200 are in accordance with the specifications prescribed by the SLAS.

Similar to the array of sampling regions 102 of the microtiter substrate 100, the rigid base 200 shown in FIG. 5A and FIG. 5B comprises 96 holes 206 arranged in a 3:2 rectangular matrix. Alternatively, the number of holes 206 on the rigid base 200 can vary, such as 6, 24, 384, or 1536, as specified according to ANSI/SLAS standards. Rigid bases 200 with different number of holes 206 are used for accommodating microtiter substrates 100 with the corresponding number of sampling regions 102.

To effectively perform assays, one microtiter substrate 100 can be attached or mated to the rigid base 200, specifically to the upper surface 202. The mated microtiter substrate 100 can subsequently be detached or removed from the rigid base 200.

The microtiter substrate 100 is attachable to the first surface of the rigid base 200. In the representative embodiment, this first surface refers to the upper surface 202. However, it would be readily understood by the skilled person that the rigid base 200 may be configurable in other embodiments such that microtiter substrate 100 is attachable to the lower surface 204. The microtiter substrate 100 is attachable to the upper surface 202 at a particular orientation such that the array of sampling regions 102 corresponds to the array of holes 206. For example, in a 96-well type microtiter substrate 100 and rigid base 200 as shown in FIG. 1, FIG. 5A, and FIG. 5B, each pair of sampling region 102 and hole 206 match with each other and shares a common axis. To facilitate and maintain the mating of the microtiter substrate 100 to the rigid base 200 at the correct orientation, each microtiter substrate 100 may comprise a set of receptacles 112, and the rigid base 200 may comprise a set of shaped ribs 210 that have small space clearances between them and the top surface 202 of the rigid base 200. The microtiter substrate 100, when bent lengthwise by a compressive force 106, can be guided into the small space clearance created between the shaped ribs 210 and the top surface 202 of the rigid base 200. The shaped ribs 210 may also have a tapered slope to facilitate the location of the microtiter substrate 100 onto the rigid base 200. The microtiter substrate 100 may have protrusions 208 extending from the upper surface 202 thereof. The receptacles 112 may comprise openings, indentations, or female fastening elements, and the protrusions 208 may comprise studs or male fastening elements, as readily known to the skilled person.

In the representative embodiment, the set of receptacles 112 comprises a pair of openings 112 through the microtiter substrate 100, and the rigid base 200 comprises a corresponding pair of protrusions 208. The pair of openings 112 is disposed on the microtiter substrate 100 away from the sampling regions 102, such that the pair of openings 112 will not be in contact with any liquid sample contained on the sampling regions 102. The pair of protrusions 208 is engaged or coupled, e.g. by a physical fastening connection and/or to form an interference fit, with the pair of openings 112 for mating the microtiter substrate 100 to the rigid base 200 at the precise orientation. FIG. 6 shows various forms of the protrusions 208 to accurately engage or couple with the openings 112. For example, each protrusion 208 may be of a half round form 208a, a conical form 208b, or a cylindrical taper form 208c. The protrusions 208 may also be of other shapes and forms. Although the representative embodiment shows two protrusions 208 to pair with two openings 112, the number of protrusions 208 and openings 112 can be more. A larger number of protrusions 208 and openings 112 provides higher attachment fidelity, but limit the ease of detaching or removing the microtiter substrate 100 from the top surface 202 of the rigid base 200 after use.

The rigid base 200 may comprise an exterior portion 220 on the sides thereof. The exterior portion 220 has a substantially flat or planar surface to allow for human fingers, or even robotic grippers or actuators, to grasp the rigid base 200 for transport. The exterior portion 220 surrounds the microtiter substrate 100 when mated to the rigid base 200, such that during transportation of the rigid base 200, neither the human fingers nor the robotic grippers / actuators can have physical contact with any of the other parts of the rigid base 200 other than the exterior portion 220. The exterior portion 220 prevents the human fingers and/or robotic grippers / actuators from contacting the mated microtiter substrate 100 which could potentially cause damage or contamination.

With the microtiter substrate 100 mated to the upper surface 202, the array of sampling regions 102 and array of holes 206 are aligned with each other. To create such an alignment, the array of sampling regions and the array of holes 206 have an identical predetermined arrangement, such that one sampling region 102 corresponds to one hole 206. This identical predetermined arrangement is in accordance to the specifications in the ANSI/SLAS standards, such as that of a 96-well type microtiter configuration. Each pair of sampling region 102 and hole 206 correspond to or match with each other and shares a common axis, and each hole 206 is wider than each sampling region 102. Thus, for a pair or set of sampling region 102 and hole 206, the size of the hole 206 is larger than the corresponding sampling region 102. When the sampling regions 102 contain the liquid samples, the size difference between each pair of a sampling region 102 and a hole 206 allows the microtiter substrate 100 to fit onto rigid base 200. When viewing directly through the holes 206 from the second surface of the rigid base 200, i.e. from the upper surface 202 when the microtiter substrate 100 is mated to the lower substrate 204, it can be seen that each sampling region 102 resides within the corresponding hole 206 in the rigid base 200.

The mated microtiter substrate 100 can be detached or removed from the upper surface 202 of the rigid base 200 by inverting it and tapping it strongly. During the detachment or removal process, the rigid base 200 can be held over a bin for direct disposal of the microtiter substrate 100 into it.

Referring to FIG. 5A and FIG. 5B, the rigid base 200 comprises small through holes, e.g. pinholes 222, extending through the upper surface 202 and lower surface 204. In the representative embodiment, the pinholes 222 are positioned on the rigid base 200 for facilitating controlled removal of the mated microtiter substrate 100. Each pinhole 222 allows for the insertion of a thin object, e.g. paper clip or pipette tip, to assist in the removal process by pushing out the mated microtiter substrate 100. Moreover, positioning one pinhole 222 at the centre of the rigid base 200 enables optimal bending of the microtiter substrate 100 for removal thereof. The pushing and bending of the microtiter substrate 100 helps to displace it from the hold of the protrusions 208 as well as the shaped ribs 210.

During this bending of the microtiter substrate 100 for detachment, it is possible for the liquid samples located on the sampling regions 102 to be displaced. In one embodiment with reference to FIG. 2, a liquid sample 22 is contained on the sampling region 102g of the microtiter substrate 100g. The pinning behaviour at the liquid sample 22 potentially resists the gravitational force acting on the liquid sample 22, preventing it from falling off. The rigid base 200 can be placed over a heated surface, e.g. a hot plate, bringing the lower surface 204 to close proximity to a heating source. This allows for good maintenance of temperature of the liquid samples, which is advantageous for purposes such as incubation. A blotting paper can be used to dry out all the liquid samples on the sampling regions 102 simultaneously by capillary action.

In the representative embodiment, the apparatus 20 may further comprise a lid 300 for attaching to and detaching from the rigid base 200. Specifically, the lid 300 is used for covering the top portion of the rigid base 200 to prevent ambient dust and other contaminants from collecting on a mated microtiter substrate 100 and on the rigid base 200, as well as to reduce the rate of evaporation of the liquid samples placed on the sampling regions 102 of the microtiter substrate 100. With reference to FIG. 7A and FIG. 7B, the lid 300 can be handled on its shorter sides for placing onto and removing from the top portion of the rigid base 200, particularly by making use of the cut-out portions 218 of the rigid base 200.

Referring back to FIG. 5, the top portion of the rigid base 200 comprises an upper edge portion 224, e.g. ridges, grooves, and/or ledges as readily known to the skilled person, running along a substantial perimeter of the rigid base 200 to allow the lid 300 to reside thereon. The lid 300 may be attached to the rigid base 200 in one or more orientations. If there is only one correct orientation, and in order to ensure the lid 300 can be attached correctly relative to the rigid base 200, the lid 300 comprises a chamfer portion 302 at one of its corners, as shown in FIG. 7A and FIG. 7B. Correspondingly, the top portion of the rigid base 200 comprises a chamfer portion 226 at one of its corners, as shown in FIG. 5A. The alignment of the chamfer portions 302 and 226 ensures that the lid 300 is attached to the rigid base 200 at the correct orientation. It would be readily known to the skilled person that other methods of ensuring the correct orientation can be used besides the chamfer portions 302 and 226, e.g. rounded or filleted portions, engaging clips, latches, etc.

In the representative embodiment, the apparatus 20 comprises a communications system connected to the rigid base for wireless communication of information, i.e. transmitting and receiving of information, such as by means of RFID or Near Field Communication (NFC). The information can be communicated to an external communication device, e.g. smartphone, tablet, notebook / laptop, or any NFC-enabled device, when it is placed near the apparatus 20. In the representative embodiment, the information is communicated to an NFC-enabled device when it is placed near a first communication device of the communications system, e.g. an NFC tag 228, disposed on or attached to the rigid base 200. By positioning the NFC-enabled device near the NFC tag 228, the NFC-enabled device can read and write data on the NFC tag 228, i.e. perform communication of information there between. In order to ensure maximum signal strength, the NFC tag 228 is disposed on or near the top portion of the rigid base 200. As shown in FIG. 5A, the NFC tag 228 is positioned at one of the corners at the top portion of the rigid base 200 to reduce possibility of the liquid samples coming in contact with the NFC tag 228 during dispensation.

The information is retrieved from a remote computing system and/or stored on the NFC tag 228 prior to the wireless communication of the information with the NFC-enabled device. The information comprises data associated with the liquid samples that are in use for assays and other procedures. For example, the data may be related to the date and time of the assays, identity of the user or practitioner, composition of the liquid samples, and results of the assays, etc. The skilled person would readily appreciate that other types of data can also be communicated to the NFC-enabled device from the NFC tag 228. The skilled person would also appreciate that the NFC tag 228 has a finite storage capacity and there is a limitation on the amount of data that can be stored on the NFC tag 228. Upon accessing and receiving the information from the NFC tag 228, the NFC-enabled device can process the information. The processing of the information can be performed locally at the NFC-enabled device, and/or relayed to servers, computing systems, smartphones or tablets. For example, the NFC-enabled device can disseminate and transmit the information to a remote server or the cloud to coordinate more comprehensive procedures in the laboratory, or to coordinate a collective assay procedure whereby several assay results from different laboratories are collected and transmitted to a central server or the cloud.

In some embodiments, the NFC tag 228 may communicate information to the NFC-enabled device when the rigid base 200 is uncovered. In some other embodiments, the NFC tag 228 can do the same even if the rigid base 200 is covered with the lid 300. The position of the NFC tag 228 on the top portion of the rigid base 200 is such that the NFC tag 228 can be as close to the lid 300 as possible when the lid 300 is attached to cover the liquid samples carried by the array of sampling regions 102 on the mated microtiter substrate 100. The communications system of the apparatus 20 may further comprise a second communication device disposed on the lid 300. The second communication device may be a top loop antenna 304 disposed on the top surface 306 of the lid 300, as shown in FIG. 7A. The top loop antenna 304 is communicatively linked with the NFC tag 228 such that the information stored on or retrieved by the NFC tag 228 can be communicated to the NFC-enabled device via the top loop antenna 304.

To improve the communication link between the top loop antenna 304 and the NFC tag 228, the lid 300 may further comprise a bottom loop antenna 308 disposed on the bottom surface 310 of the lid 300. The top loop antenna 304 is communicatively linked to the bottom loop antenna 308 by a conductive pathway 312, as shown in FIG. 7B. The bottom loop antenna 308 is positioned at one of the corners at the bottom surface 310 of the lid 300 so that it corresponds to the position of the NFC tag 228 on the rigid base 200. Specifically, when the lid 300 is attached to the rigid base 300, the bottom loop antenna 308 is positioned directly above and facing the NFC tag 228. The minimal space between them allows for wireless communication of information from the NFC tag 228 to the bottom loop antenna 308 via NFC.

Thus, if the rigid base 200 is covered with the lid 300, the top loop antenna 304 on the lid 300 provides a conduit for electronic signals transmitted and received by the NFC-enabled device for communication with the NFC tag 228. The NFC enabled device has to be located such that its active communication area resides substantially within that of the top loop antenna 304, such as by placing the NFC-enabled device proximately above the top loop antenna 304 or on the lid 300. The information stored on or retrieved by the NFC tag 228 can be sequentially communicated to the bottom loop antenna 308, conductive pathway 312, top loop antenna 304, and the NFC-enabled device.

In the representative embodiment shown in FIG. 7A, the lid 300 is a laminated printed circuit board (PCB) with the conductive top loop antenna 304 on its top surface 306. As the lid 300 comprises electronic and conductive components for the communications system, the lid 300 may be made of a dielectric material, i.e. an electric-insulating material, in order to attenuate the effects of electromagnetic interference. Similarly, the rigid base 200 is made of a dielectric material to minimize electronic communication interference with the NFC tag 228.

To assist in some assays or experimental procedures, the apparatus 20 may further comprise a set of sensors 314 or liquid retaining medium 316. Referring to FIG. 7B, the set of sensors 314 may comprise single or a plurality of self-powered, low profile, and data-logging sensors 314 that may be disposed on the bottom surface 310 of the lid 300. In the representative embodiment with reference to FIG. 5A, the space between the top surface 202 of the rigid base 200 and the bottom surface 310 of the lid 300 is sufficient for accommodating the sensors 314. The sensors 314 are configured for collecting and logging information, such as data associated with the liquid samples, and the ambient conditions of the assays and procedures, e.g. temperature and humidity etc. The sensors 314 may also be configured to perform optical sensing. In order to prevent or at least reduce systematic error in the results of the optical sensing, the material of the rigid base 200 is made of an opaque material to reduce reflection and limit optical interference between the sampling regions 102. A liquid retaining medium 316 such a microfiber cloth may serve to reduce the degree of evaporative losses of liquid samples in the microtiter substrate 100 when they need to be incubated over long periods.

Various embodiments of an apparatus 20 have thus been disclosed hereinabove. An illustration of the representative embodiment of the apparatus 20 comprising the microtiter substrates 100, rigid base 200, and lid 300 is shown in FIG. 8. The apparatus 20 is operable on standard microplate equipment / instruments, and the various modular components are typically used in combination together, but may also be used in isolation, such as for implementation with other handling systems and assemblies. A method 600 for handling of liquid samples for assays is described hereinafter. In a representative embodiment with reference to FIG. 9, the method 600 is performed with the representative apparatus 20 described hereinabove.

The method 600 comprises a step 602 of providing the rigid base 200 of the apparatus 20, and a step 604 of providing the set of microtiter substrates 100. To prepare the liquid samples for the assays, one microtiter substrate 100 is retrieved from the set of microtiter substrates 100 in a step 606. The microtiter substrate 100 is subsequently attached to or mated to a first surface of the rigid base 200 in a step 608. As described above, in the representative embodiment, the first surface refers to the top surface 202. With the microtiter substrate 100 mated to the upper surface 202, each sampling region 102 of the mated microtiter substrate 100 resides within the corresponding hole 206 of the rigid base 100. In a step 610, the liquid samples are introduced to the sampling regions 102 of the mated microtiter substrate 100. The introduction of the liquid samples can be by means of manual or automated pipette instruments or other dispensing mechanisms as known to the skilled person.

The sampling regions 102 are configured for carrying the liquid samples within the corresponding holes 206 and without physical contact with the rigid base 200 in or during the preparation for the assays of the liquid samples. The liquid samples are subsequently subjected to assays and/or other analytical and/or experimental procedures in a step 612 of the method 600. Upon completion of the assays of the liquid samples, the microtiter substrate 100 that is still attached to the rigid base 200 is detached or removed in a step 614. A decision in a step 616 can be made to continue or stop the process. Continuation may involve the detached microplate substrate 100 being treated and then reused by repeating steps 606, 608, 610, 612, 614, and 616. Alternatively it may involve discarding the detached microtiter substrate 100 and using another microtiter substrate 100 to repeat steps 606, 608, 610, 612, 614, and 616.

An advantage of using the method 600 is that multiple batches of liquid samples can be contained in different microtiter substrates 100 and analysed under different iterations of the assays. The microtiter substrates 100 can be quickly loaded and removed forfurther processing or discarded. In other words, the apparatus 20 provides a rigid base 200 for use with disposable microtiter substrates 100. As the liquid samples do not contact the rigid base 200, no washing is required for the rigid base 200. In addition, the microtiter substrates 100 are thinner and more flexible then conventional monolithic substrates, and thus may be less expensive to produce and constitute a lower waste disposal footprint when discarded.

As described above, the apparatus 20 comprises a communications system for wireless communication of information with an NFC-enabled device using an NFC tag 228 disposed on the rigid base 200. The communications system enables information about the liquid samples to be efficiently retrieved and disseminated. Users and practitioners can quickly know the results of the assays of a particular batch of liquid samples. Further, by identifying the liquid samples contained on a microtiter substrate 100, the correct disposal procedure for the microtiter substrate 100 can be established. The information could also inform the user or practitioner the number of times a particular rigid base 200 has been used, i.e. the number of iterations of assays. Some laboratories may regulate that the rigid base 200 be washed periodically after a certain number of iterations of assays for proper maintenance thereof.

In the foregoing detailed description, embodiments of the present disclosure in relation to an apparatus and method for handling of liquid samples for assays are described with reference to the provided figures. The description of the various embodiments herein is not intended to call out or be limited only to specific or particular representations of the present disclosure, but merely to illustrate non-limiting examples of the present disclosure. The present disclosure serves to address at least some of the mentioned problems and issues associated with the prior art. Although only some embodiments of the present disclosure are disclosed herein, it will be apparent to a person having ordinary skill in the art in view of the present disclosure that a variety of changes and/or modifications can be made to the disclosed embodiments without departing from the scope of the present disclosure. The scope of the present disclosure as well as the scope of the following claims is not limited to embodiments described herein.

Brief Description of the Drawings FIG. 1 is an illustration of a top planar view of a microtiter substrate of an apparatus for handling of liquid samples for assays, in accordance with an embodiment of the present disclosure. FIG. 2 is an illustration of cross-sectional views of a sampling region of the microtiter substrate of FIG. 1, in accordance with an embodiment of the present disclosure. FIG. 3 is an illustration of a partially bent microtiter substrate of FIG. 1, in accordance with an embodiment of the present disclosure. FIG. 4 is an illustration of a perspective view of the microtiter substrate of FIG. 1 with a protective film, in accordance with an embodiment of the present disclosure. FIG. 5A is an illustration of a top perspective view of a rigid base of an apparatus for handling of liquid samples for assays, in accordance with an embodiment of the present disclosure. FIG. 5B is an illustration of a bottom perspective view of the rigid base of FIG. 5A, in accordance with an embodiment of the present disclosure. FIG. 6 is an illustration of cross-sectional views of a protrusion of the rigid base of FIG. 5A, in accordance with an embodiment of the present disclosure. FIG. 7A is an illustration of a top planar view of a lid of an apparatus for handling of liquid samples for assays, in accordance with an embodiment of the present disclosure. FIG. 7B is an illustration of a bottom view of the lid of FIG. 7A, in accordance with an embodiment of the present disclosure. FIG. 8 is an illustration of an exploded view of an apparatus for handling of liquid samples for assays, in accordance with an embodiment of the present disclosure. FIG. 9 is an illustration of a process flowchart of a method for handling of liquid samples for assays, in accordance with an embodiment of the present disclosure.

Claims (5)

1. The claims defining the invention are as follows:

   1. An apparatus for handling of liquid samples for assays, the apparatus comprising: a set of microtiter substrates, each microtiter substrate comprising an array of sampling regions for carrying the liquid samples; and a rigid base comprising opposing first and second surfaces, and an array of holes extending through the first and second surfaces, the rigid base configured for mating or removing one microtiter substrate to the first surface, wherein each hole is wider than each sampling region, and the array of holes and the array of sampling regions are in an identical predetermined arrangement, such that one sampling region corresponds to one hole; and wherein when one microtiter substrate is mated to the first surface of the rigid base: each sampling region of the mated microtiter substrate resides within the corresponding hole of the rigid base; the sampling regions are accessible, enabling introduction of the liquid samples to the sampling regions; and the sampling regions are configured for carrying the liquid samples within the corresponding holes and without physical contact with the rigid base in preparation for the assays of the liquid samples.
2. 2. The apparatus as in claim 1, further comprising a communications system connected to the rigid base for wireless communication of information with an external communication device.
3. 3. The apparatus as in claim 1, each microtiter substrate comprising a set of receptacles disposed away from the array of sampling regions; and the rigid base comprising a set of shaped ribs and a set of protrusions, wherein one microtiter substrate can be bent lengthwise with a compressive force and guided into the spaces underneath the shaped ribs to locate the microtiter substrate onto the rigid base, and the set of receptacles of one microtiter substrate and the set of protrusions of the rigid base can be coupled to form an interference fit for mating the microtiter substrate to the rigid base.
4. 4. The apparatus as in claim 1, the rigid base comprising pinholes extending through the first and second surfaces, the pinhole configured for facilitating removal of the mated microtiter substrate.
5. 5. A method for handling of liquid samples for assays, the method involves: providing a rigid base comprising opposing first and second surfaces, and an array of holes extending through the first and second surfaces; providing a set of microtiter substrates, each microtiter substrate comprising an array of sampling regions for carrying the liquid samples, wherein each hole is wider than each sampling region, and wherein the array of holes and the array of sampling regions are in an identical predetermined arrangement, such that one sampling region corresponds to one hole; retrieving one microtiter substrate from the set of microtiter substrates; mating the microtiter substrate to the first surface of the rigid base; accessing the sampling regions through the corresponding holes from the second surface, wherein each sampling region of the mated microtiter substrate resides within the corresponding hole of the rigid base; introducing the liquid samples to the sampling regions of the mated microtiter substrate, wherein the sampling regions are configured for carrying the liquid samples within the corresponding holes and without physical contact with the rigid base in preparation for the assays of the liquid samples; and detaching the microtiter substrate from the rigid base, wherein the rigid base can be reused while the microtiter substrate is further processed or discarded.